In the Phase 3 study MK-8591A-053, investigators compared the investigational once-daily two-drug regimen doravirine/islatravir (DOR/ISL 100/0.25 mg) with the established three-drug single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in treatment-naïve adults.

The central question was straightforward but clinically relevant: can a non-INSTI two-drug regimen deliver virologic efficacy comparable to one of the most widely used integrase inhibitor–based standards?

Study Population and Design

The trial enrolled 536 participants across 116 sites in 20 countries, creating a geographically diverse and contemporary cohort. Recruitment spanned Latin America, North America, Africa, Europe, and Asia/Pacific regions. Median age was 32 years, and 25% of participants were female at birth. Viral diversity was notable, with subtype B accounting for approximately 53% of infections, subtype C 19%, and non-B/non-C strains 28%.

Clinical presentation at baseline reflected real-world variability. Median CD4 count was 370 cells/mm³, and 17% of participants had CD4 counts below 200 cells/mm³. Viral burden was substantial: median HIV-1 RNA was approximately 55,000 copies/mL, 37% had levels exceeding 100,000 copies/mL, and 10% were above 500,000 copies/mL. These are populations in which durability and resistance barriers are tested early.

Participants were randomized in a double-blind design to receive either DOR/ISL or BIC/FTC/TAF. The primary endpoint was HIV-1 RNA <50 copies/mL at Week 48 using the FDA Snapshot approach, with a prespecified noninferiority margin of −10%.

Virologic Outcomes at Week 48

At Week 48, 91.8% of participants receiving DOR/ISL achieved HIV-1 RNA <50 copies/mL, compared with 90.6% in the BIC/FTC/TAF arm. The treatment difference was 1.2% (95% CI −3.7, 6.2), meeting the statistical criteria for noninferiority.

Efficacy was consistent across subgroups, including those with high baseline viral load, low CD4 counts, and across viral subtypes. Discontinuations due to lack of efficacy were uncommon: four in the DOR/ISL group and two in the comparator arm.

From a virologic standpoint, the two-drug regimen performed comparably to a modern three-drug integrase inhibitor–based standard.

Resistance Profile

Treatment-emergent resistance was observed in two of 269 participants (<1%) in the DOR/ISL group. In both cases, reverse transcriptase mutations associated with doravirine resistance were detected, including substitutions such as Y188L and V106A. Phenotypic testing demonstrated high-level resistance to doravirine, while susceptibility to islatravir was maintained.

In one case, plasma drug concentrations suggested possible incomplete adherence early in treatment; in the other, drug levels were detectable at study visits. No corresponding resistance signal was reported in the BIC/FTC/TAF arm.

Although rare, these findings underscore a principle inherent to two-drug strategies: the genetic barrier to resistance depends heavily on adherence and on the resistance profile of each component.

Immune Recovery and Safety

Immune reconstitution was similar between groups. At Week 48, mean CD4 count increased by 218 cells/mm³ in the DOR/ISL arm and 226 cells/mm³ in the BIC/FTC/TAF arm, with no clinically meaningful difference.

Safety outcomes were broadly comparable. Any adverse event occurred in 84.8% of participants receiving DOR/ISL and 88.0% receiving BIC/FTC/TAF. Serious adverse events were reported in 8.2% and 7.1%, respectively. Discontinuations due to adverse events were infrequent in both arms.

Two drug-related serious adverse events occurred in the DOR/ISL group — one case of drug reaction with eosinophilia and systemic symptoms (DRESS) and one drug-induced liver injury that did not meet Hy’s law criteria. Three hepatitis B infections were observed in the DOR/ISL arm among participants without baseline hepatitis B immunity; one individual transitioned to BIC/FTC/TAF with subsequent resolution of infection. Two deaths occurred in the comparator arm and were not considered drug-related.

Weight and Metabolic Considerations

Weight gain was similar between regimens. At Week 48, mean weight increased by 3.6 kg in the DOR/ISL group and 3.9 kg in the BIC/FTC/TAF group. The between-group difference of −0.3 kg (95% CI −1.5, 0.9) was not statistically significant.

In practical terms, the non-INSTI two-drug regimen did not demonstrate a metabolic advantage over integrase inhibitor–based therapy during the first year.

Expanding First-Line Options

Doravirine is an established non-nucleoside reverse transcriptase inhibitor, while islatravir represents a nucleoside reverse transcriptase translocation inhibitor with multiple mechanisms of action, including inhibition of translocation and delayed chain termination. The combination offers a mechanistically distinct alternative to integrase-based regimens.

The Week 48 results demonstrate that DOR/ISL (100/0.25 mg) is noninferior to BIC/FTC/TAF for initial treatment of HIV-1, with high rates of viral suppression, comparable immune recovery, and a similar safety profile.

These findings do not displace integrase inhibitor–based therapy as a standard of care. Rather, they broaden the therapeutic landscape. In contemporary HIV medicine, flexibility is increasingly important. Not every patient requires the same mechanism, and not every clinical situation favors an integrase-based approach.

The value of this study lies in diversification. It confirms that a non-INSTI two-drug regimen can achieve control comparable to a three-drug standard in a globally representative, treatment-naïve population.

In an era where treatment goals remain unchanged — durable viral suppression, immune recovery, and long-term safety — expanding validated options is itself progress.

In the Phase 3 ARTISTRY-1 study, presented by Professor Chloe Orkin, investigators evaluated the efficacy and safety of switching from complex antiretroviral regimens to a once-daily single-tablet combination of bictegravir and lenacapavir (BIC/LEN).

The study did not aim to demonstrate superiority. It aimed to answer something more fundamental: can treatment be simplified without losing control?

A Population Often Overlooked

The ARTISTRY-1 population reflects a group that is frequently underrepresented in modern registrational trials.

Participants had been living with HIV for a median of 28 years. More than 76% were aged 55 or older. Over 80% had a documented history of antiretroviral resistance. Many were taking three or more pills per day, and 39% required twice-daily dosing.

Complex regimens were defined broadly and included boosted protease inhibitor combinations, regimens with multiple third agents, parenteral agents in combination with oral therapy, or dosing schedules more frequent than once daily.

Comorbidity burden was substantial:

• Dyslipidemia in 68%
• Hypertension in 50%
• Diabetes or hyperglycemia in 24%
• Chronic kidney disease in 14%
• More than half had two or more comorbid conditions
• Nearly 61% were taking at least two concomitant non-HIV medications

This is not a marginal population. It represents long-term survivors with accumulated treatment history, resistance, and age-related health complexity.

Many current single-tablet regimens are not options for them due to historical resistance, intolerance, contraindications, or drug–drug interactions.

Study Design and Primary Outcome

ARTISTRY-1 was a randomized, open-label, multicenter Phase 2/3 trial. Adults with HIV-1 RNA <50 copies/mL on stable complex regimens for at least six months were randomized 2:1 to switch to BIC/LEN or to continue their baseline regimen.

The primary endpoint at Week 48 was the proportion of participants with HIV-1 RNA ≥50 copies/mL (FDA Snapshot algorithm), with a noninferiority margin of 4%.

At Week 48:

• 0.8% of participants in the BIC/LEN group had HIV-1 RNA ≥50 copies/mL.
• 1.1% in the complex regimen group met this endpoint.
• 96% of those switched to BIC/LEN maintained HIV-1 RNA <50 copies/mL, compared with 93.5% in the control group.

The difference met criteria for noninferiority.

Importantly, no treatment-emergent resistance to bictegravir or lenacapavir was detected through Week 48. The few participants with viral rebound in the BIC/LEN group either resuppressed or had low-level viremia without changing therapy.

CD4 counts remained stable in both groups.

In a population with high rates of historical NRTI, NNRTI, and protease inhibitor resistance — and some prior integrase mutations — maintaining suppression without emergent resistance is clinically significant.

Safety Profile and Metabolic Effects

Adverse events occurred at similar rates in both groups. Any adverse event was reported in 82.2% of participants in the BIC/LEN arm and 84.4% in those continuing complex regimens. Serious adverse events occurred in 14.0% and 11.8%, respectively.

Discontinuations due to adverse events were infrequent:

• 1.6% in the BIC/LEN group
• 0.5% in the complex regimen group

Five deaths occurred in the BIC/LEN arm, none considered related to study treatment.

Notably, fasting lipid parameters improved after switching to BIC/LEN. Total cholesterol, LDL cholesterol, triglycerides, and total cholesterol-to-HDL ratio showed statistically significant reductions compared with continued complex regimens. In a population where nearly two-thirds had dyslipidemia at baseline, these changes may have clinical relevance.

Treatment Satisfaction: A Measurable Difference

Beyond virologic outcomes, ARTISTRY-1 assessed treatment satisfaction using the HIV Treatment Satisfaction Questionnaire.

At baseline, satisfaction scores were similar between groups. After switching to BIC/LEN, treatment satisfaction increased significantly by Week 4 and remained higher through Week 48 (P < 0.0001 at multiple timepoints).

For individuals taking multiple tablets for decades, simplification is not cosmetic. It affects daily routine, adherence confidence, and long-term sustainability.

Why This Study Matters

HIV innovation often focuses on treatment-naïve individuals or long-acting injectable strategies. ARTISTRY-1 addresses a different reality: people who achieved suppression years ago but remain on regimens that are complex because history limited their options.

This is a community that has accumulated resistance patterns, comorbidities, and polypharmacy. They are not failing therapy — but they have been difficult to simplify.

The combination of bictegravir, a high-barrier integrase inhibitor, with lenacapavir, a first-in-class capsid inhibitor with a novel resistance profile, offers a mechanistically distinct approach that enables simplification without compromising efficacy.

The results from ARTISTRY-1 demonstrate that in treatment-experienced, virologically suppressed adults on complex regimens, switching to once-daily BIC/LEN maintains viral suppression, shows no emergent resistance through 48 weeks, is generally well tolerated, improves lipid parameters, and increases treatment satisfaction.

This is not a speculative advance. It is an evidence-based option for a population that has long required individualized, often complicated solutions.

Simplification, in this context, is not about convenience. It is about sustainability for people living with HIV across decades of care.

We are achieving unprecedented success in HIV control. Yet sexually transmitted infections (STIs) are resurging — rapidly, globally, and unevenly.

The question posed was not only epidemiological. It was existential for HIV medicine: have we entered an era of denial, doom, or destiny when it comes to STIs?

The Numbers We Cannot Ignore

The epidemiological backdrop is stark.

In 2024, more than 2.2 million STIs were reported in the United States alone. Compared to 2015:

• Gonorrhea cases increased by 37% (from ~395,000 to over 543,000).
• Total syphilis cases rose by 155%.
• Congenital syphilis surged by nearly 700%, from 495 to 3,941 cases.

Chlamydia rates remained high, hovering around 1.5 million annual cases.

Behind these aggregate numbers lies a more nuanced pattern. Nearly one-third of primary and secondary syphilis cases in 2024 were diagnosed among men who have sex with men (MSM). Given that MSM comprise roughly 5% of adult men, the incidence in this population is more than 80 times higher than in heterosexual men.

At the same time, women have become the second most affected group. The consequences are severe: the rise in congenital syphilis mirrors increasing primary and secondary syphilis rates among women aged 15–44. The rate of primary and secondary syphilis in this group reached 14.7 per 100,000 in 2024 — translating into thousands of preventable neonatal infections.

Globally, the picture is equally concerning. In a cohort of over 3,000 women in sub-Saharan Africa receiving oral PrEP, nearly one-third had at least one STI at baseline, and incidence exceeded 49 cases per 100 person-years. Most infections were asymptomatic.

The era of HIV viral suppression has not translated into STI control.

Syphilis: An Old Infection, Persistent Challenges

Despite decades of experience, syphilis remains diagnostically and operationally frustrating.

Serologic testing cannot reliably distinguish between past infection, reinfection, or treatment failure. It is an imperfect surrogate for treatment response. Diagnosing congenital syphilis remains particularly complex. And vaccine development has progressed slowly.

Even treatment — long considered straightforward — has been challenged by periodic shortages of benzathine penicillin formulations. In 2024, alternative imported supplies had to be authorized in the United States due to Bicillin L-A shortages.

One reassuring update came from a randomized trial comparing one dose versus three weekly doses of benzathine penicillin G for early syphilis. In 249 participants — 61% of whom were living with HIV — a single 2.4 million unit intramuscular dose was non-inferior to the traditional three-dose regimen. Serologic response rates at six months were 76% in the single-dose group versus 70% in the three-dose group, with similar outcomes among people with HIV.

This finding simplifies management. But it does not address the larger structural problem: delayed diagnosis, inconsistent screening, and missed treatment — particularly in pregnancy.

And, as Dr. Marrazzo reminded the audience, not every rash is syphilis. Emerging pathogens, including sexually transmitted dermatophyte infections such as Trichophyton mentagrophytes genotype VII reported in New York in 2024, can mimic eczema or psoriasis. Diagnostic vigilance remains essential.

Gonorrhea and the Superbug Threat

If syphilis represents a diagnostic challenge, gonorrhea represents a microbiological one.

Antimicrobial resistance in Neisseria gonorrhoeae continues to expand. In European surveillance data from 24 countries, resistance to ciprofloxacin reached 95% in some regions. Resistance to cefixime and rising minimum inhibitory concentrations to ceftriaxone are particularly concerning in parts of Asia. Data from sub-Saharan Africa remain limited.

Two new oral antibiotics have recently entered the landscape: zoliflodacin and gepotidacin, both targeting bacterial type II topoisomerases via novel mechanisms. In trials, microbiologic cure rates for uncomplicated urogenital gonorrhea reached approximately 91–93%, comparable to standard therapy.

Yet enthusiasm is tempered by evolutionary biology. Modeling studies suggest that holding new antibiotics in reserve or deploying them sequentially may paradoxically shorten their useful lifespan. Moreover, certain gonococcal lineages already harbor mutations that confer cross-resistance between these agents.

The race between innovation and resistance is ongoing — and far from settled.

Doxy-PEP: A Disruptive Intervention

Perhaps the most immediately transformative development discussed at CROI was doxycycline post-exposure prophylaxis (Doxy-PEP).

Taken as 200 mg within 72 hours after condomless sex, Doxy-PEP has demonstrated substantial reductions in syphilis and chlamydia among MSM and transgender women in U.S. studies. In Seattle and San Francisco, implementation was associated with sharp declines in syphilis cases among cisgender men.

Unexpectedly, some regions observed declines among cisgender women as well, despite low reported use — suggesting potential indirect effects through sexual networks.

However, the picture is more complex elsewhere. In a Kenyan trial among cisgender women on PrEP, Doxy-PEP showed no significant reduction in STI incidence — largely due to low adherence. A pilot study using weekly directly observed doxycycline demonstrated lower chlamydia incidence, but implementation feasibility remains uncertain.

Meanwhile, concerns about resistance are growing. In French data from the DOXYVAC study, gonococcal isolates from Doxy-PEP users were more likely to show decreased susceptibility to cefixime and to harbor multiple resistance genes, including mosaic penA alleles. No ceftriaxone resistance was detected — but surveillance is critical.

Doxy-PEP may be a medium-term solution to a long-term problem. It is unlikely to replace the need for durable immunity through vaccination.

Vaccines and Self-Testing: Cautious Optimism

Perhaps the most hopeful segment of the plenary focused on vaccines.

Retrospective analyses suggest that the group B meningococcal vaccine (4CMenB) provides approximately 35–41% protection against gonorrhea acquisition. Dynamic modeling in high-risk populations suggests this level of efficacy could justify routine immunization in selected groups. A large phase 2 randomized trial of 4CMenB for gonorrhea prevention is nearing completion, with over 2,300 participants across multiple countries.

Other vaccine platforms, including generalized membrane antigen (GMMA) candidates, are in development.

Diagnostics are evolving as well. In the past two years, the first FDA-approved over-the-counter tests for chlamydia, gonorrhea, and syphilis have become available, including fully at-home nucleic acid amplification tests. A dual treponemal/non-treponemal rapid test is under regulatory review.

These tools could decentralize testing and reduce reliance on syndromic management — particularly important in low- and middle-income countries, where most STIs in women are asymptomatic.

But innovation must be accompanied by affordability and equitable access.

Between Control and Complacency

The plenary concluded with a sobering reflection.

HIV control has advanced dramatically through antiretroviral therapy and PrEP. Yet STI prevention has not kept pace. Behavioral shifts, power imbalances, limited screening access, and structural inequities continue to shape transmission patterns.

No antibiotic, prophylactic strategy, or vaccine will fully compensate for these realities.

The resurgence of syphilis and the emergence of resistant gonorrhea do not signal failure — but they do demand renewed urgency. Innovation in diagnostics, treatment, vaccine development, and implementation must accelerate. Screening during pregnancy must be strengthened. Resistance surveillance must expand globally.

Denial is no longer possible. Doom is not inevitable. Destiny, perhaps, lies in how decisively we respond.

The era of HIV control does not mark the end of sexual health challenges — it marks the beginning of a more complex chapter.

Are we witnessing a genuine therapeutic revolution — or a moment of medical “irrational exuberance”?

Beyond Blood Sugar: A Cardiometabolic Shift

GLP-1 receptor agonists (GLP-1 RAs) were developed to treat type 2 diabetes. Their biological mechanism is well understood: they enhance glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying and act centrally to reduce appetite. In clinical trials, drugs such as semaglutide and tirzepatide lower HbA1c by as much as 2–2.3 percentage points — an impressive metabolic effect.

But glucose control is no longer the main story.

The turning point came with cardiovascular outcome trials. In the SELECT trial, semaglutide reduced major adverse cardiovascular events — heart attack, stroke or cardiovascular death — by 20% in people with established cardiovascular disease. Importantly, only about one third of that benefit could be explained by changes in waist circumference. The implication is striking: these drugs do more than induce weight loss. They appear to modify cardiovascular biology itself.

For decades, diabetes treatment focused primarily on glycemic control. GLP-1 receptor agonists altered that paradigm. For the first time, clinicians could prescribe a glucose-lowering medication that also demonstrably reduces cardiovascular risk.

The metabolic effects extend even further. In obesity trials, semaglutide produces roughly 16% body-weight reduction, while tirzepatide reaches close to 18% — translating into average losses approaching 20 kilograms in some studies. These outcomes begin to rival bariatric surgery. Clinical data now show improvements in heart failure with preserved ejection fraction, slowing of chronic kidney disease progression, resolution of metabolic dysfunction-associated steatohepatitis (MASH), and dramatic reductions — up to 64% — in sleep apnea severity.

And yet an important scientific question remains unresolved: how much of these benefits are mediated by weight loss itself, and how much reflect direct cellular and tissue-specific effects of GLP-1 signaling? If the mechanism extends beyond adiposity, we may be looking at a new class of systemic modulators rather than sophisticated appetite suppressants.

Inflammation, the Brain — and Unexpected Horizons

One of the most compelling discussions at CROI centered on inflammation. GLP-1 receptor agonists consistently reduce inflammatory markers such as C-reactive protein by 40–60% in clinical studies. Only part of this reduction can be explained by changes in body weight or glucose, suggesting intrinsic immunometabolic effects.

For populations living with chronic immune activation — including people with treated HIV — this observation is particularly intriguing. In a randomized study of semaglutide in individuals with HIV-associated lipohypertrophy, participants experienced a 19% reduction in total body fat and a 31% decrease in visceral adipose tissue. More strikingly, C-reactive protein fell by nearly 50%, alongside reductions in interleukin-6 and sCD163. Some of these changes appeared partly independent of fat loss.

Inflammation is a common thread linking cardiovascular disease, aging, neurodegeneration and metabolic dysfunction. If GLP-1 RAs influence inflammatory pathways directly, their relevance could extend well beyond obesity management.

The neurological dimension adds another layer. GLP-1 receptors are expressed in brain reward centers, and preclinical studies show reduced alcohol, nicotine and opioid seeking in animal models. Early human data are emerging. In a randomized study in alcohol use disorder, weekly semaglutide reduced laboratory alcohol consumption and craving, and even decreased cigarette use among smokers. More than twenty randomized trials are underway.

If confirmed, GLP-1 agonists may represent a new biological approach to compulsive reward behavior — a development that would fundamentally broaden their clinical scope.

The Reality Check: Durability, Aging and Access

Amid enthusiasm, the conference also presented sobering realities. In a real-world cohort of over 125,000 adults initiating GLP-1 therapy, one-year discontinuation rates were 46% among people with diabetes and 65% among those without diabetes. After stopping treatment, weight regain was rapid. A recent meta-analysis projected return to baseline weight within approximately 1.4 years after discontinuation of newer incretin therapies, with parallel loss of cardiometabolic improvements.

These data underline a critical truth: GLP-1 receptor agonists behave like chronic disease treatments. Short-term use followed by discontinuation is biologically inconsistent with the pathophysiology of obesity. Yet long-term maintenance strategies remain undefined.

Life-course considerations add further complexity. Older adults — particularly those over 75 — are underrepresented in major trials. Lean mass reduction, including around 9% decline in psoas muscle volume in some analyses, raises questions about frailty and sarcopenia. Bone density and fracture risk require additional data. At the same time, observational analyses suggest up to a 45% reduction in incident dementia among GLP-1 users, although recent Alzheimer’s trials have produced mixed results. The interaction between GLP-1 signaling and biological aging remains an open field of investigation.

Globally, the implications are immense. Roughly 27% of the world’s population could meet eligibility criteria for GLP-1 therapy. Yet current production capacity would cover only a fraction of those in need. Patent expirations beginning in 2026 in several countries, new oral formulations, and more than sixty GLP-1-based compounds in development may expand access — but without coordinated policy, inequities may widen.

A Transformation — But Not a Panacea

So, are GLP-1 receptor agonists a cure for everything?

The message from CROI 2026 was neither naïve nor dismissive. These agents have transformed diabetes and obesity care and introduced a new cardiometabolic paradigm. They show credible promise in inflammatory modulation, addiction medicine and possibly neurodegeneration. But they are not universal solutions, and their long-term safety, sustainability and accessibility remain unresolved.

Perhaps the most accurate conclusion is this: we are not at the peak of GLP-1 therapy — we are at the beginning of understanding its systemic implications.

The enthusiasm appears rational. The responsibility now is to ensure that it remains guided by evidence rather than driven by hype.

The findings do not represent a cure, nor do they support treatment interruption outside clinical trials. However, they provide early evidence that immune-based interventions might modulate post-treatment viral control.

The results presented reflect only part of the ongoing study, and several mechanistic analyses remain in progress.

Study Design and Rationale

The RIO trial evaluates two long-acting broadly neutralizing antibodies — 3BNC117-LS and 10-1074-LS — administered to individuals who initiated antiretroviral therapy (ART) early after infection and maintained sustained viral suppression.

Broadly neutralizing antibodies bind conserved regions of the HIV envelope, blocking viral entry and potentially enhancing immune-mediated clearance of infected cells. The LS modification extends half-life, allowing prolonged circulation.

The study includes analytically supervised treatment interruptions (ATI), conducted under strict safety criteria.

Participants were randomized 1:1:

• Arm A received dual bNAbs.
• Arm B received placebo.

In the first ATI phase (ATI-1), viral rebound occurred as expected across participants. In Arm B (placebo), rebound was rapid and universal. By week 10 of ATI-1, all participants had met rebound criteria.

Viral rebound was defined as either >1,000 copies/mL for six consecutive weeks or >100,000 copies/mL for two consecutive weeks, with adjudication in special cases.

This confirmed the established observation that ART cessation results in detectable viremia within weeks.

Delayed Viral Rebound in ATI-2

Participants in one arm of the study (Arm B) initially received placebo during ATI-1. After ART re-suppression, they were administered the dual bNAb combination. Following an antibody washout period of approximately 24 weeks on ART, a second treatment interruption (ATI-2) was performed.

This within-participant comparison revealed a marked shift in rebound kinetics.

During ATI-1, 100% of participants experienced viral rebound by week 20. During ATI-2, approximately 50% had not rebounded by week 20. Among those with delayed rebound, viral load rose more slowly and peaked at lower levels.

Notably, delayed rebound occurred despite only modest circulating antibody concentrations at ATI-2 start (median just under 50 µg/mL), similar to levels observed at rebound in Arm A during ATI-1. This suggests the effect may not be explained solely by passive neutralization.

Of 34 Arm B participants, 28 were included in the paired ATI-1 versus ATI-2 analysis. Two individuals with ongoing viral control during ATI-1 for nearly four years — likely post-treatment controllers — were excluded from this comparison.

As Julia Edgar noted during the discussion, “We are actively working to understand what factors distinguish those who control from those who do not — it’s unlikely to be a single mechanism.”

Is the Effect Attributable to Antibodies?

An important question raised during the session concerned causality.

Jonathan Lee (Brigham and Women’s Hospital) asked whether repeated treatment interruptions alone might alter rebound kinetics, referencing earlier ACTG data showing that sequential ATIs can influence viral dynamics.

Edgar acknowledged the analytical complexity: “It’s a bit tricky of a comparison because of the washout period and differences in antibody concentration at the start of ATI-2. But we are looking at it.”

Distinguishing between an effect of repeated ATI and a true antibody-mediated modulation remains central to interpreting the data.

If confirmed, the findings would support the hypothesis that bNAbs can induce durable immunologic changes beyond transient viral neutralization.

Mechanistic Questions: Resistance, Sensitivity, Immune Modulation

Preliminary analyses from Arm A, conducted by the Rockefeller University group, identified resistance mutations emerging primarily against 10-1074 following rebound.

Whether delayed rebounders exhibit distinct resistance patterns, altered inflammatory markers, enhanced T-cell or NK-cell responses, or reservoir changes remains under investigation.

Investigators defined a 9-week threshold for delayed rebound based on the mean time to rebound plus two standard deviations during ATI-1. Using this data-derived cutoff, two rebound phenotypes emerged in ATI-2: early rebounders (<9 weeks) and delayed rebounders (>9 weeks).

Another hypothesis raised during the discussion was viral hypersensitivity: could delayed rebound reflect unusually high sensitivity of residual virus to modest antibody concentrations?

“We don’t yet know the sensitivity profile of the viral reservoir before ATI-2,” Edgar responded. “There is likely significant inter-individual variability.”

Current analyses are evaluating viral genetics, immune phenotyping, and functional responses to determine whether the observed effect reflects persistent low-level neutralization, altered reservoir composition, immune priming, or a combination of mechanisms.

At present, no definitive mechanism has been established.

Ethical Considerations in ATI Design

The trial also prompted discussion regarding the ethics of placebo-controlled ATIs.

Community representative Peter Allen questioned whether additional placebo interruptions are justified, given that viral rebound in untreated interruption is already well characterized.

Investigators noted that when RIO was designed, controlled placebo data were still limited. As the evidence base grows, the field may reconsider whether new placebo arms remain necessary.

The exchange underscored a broader shift in HIV cure research: balancing mechanistic rigor with participant risk minimization.

Interpretation and Implications

The RIO data suggest that dual broadly neutralizing antibody exposure may modify viral rebound kinetics in approximately half of treated individuals under controlled conditions.

This does not equate to durable remission. ART remains the standard of care.

However, the findings raise the possibility that antibody-based interventions may exert immunomodulatory effects capable of shifting host–virus equilibrium, at least transiently.

The magnitude and durability of this shift — and whether it can be enhanced through combination strategies — remain open questions.

As presented, these results represent an early signal, not a conclusion.

But in a field where functional cure remains elusive, even modest changes in rebound kinetics warrant close examination.

Further data from additional study arms, including Arm C designed to assess the contribution of ATI alone (“autovaccination”), and ongoing mechanistic analyses will be critical to determine whether RIO marks a meaningful advance in immune-based HIV control.

The session, which included five interconnected presentations, highlighted two major points: the exceptional biological effectiveness of prevention drugs and emerging structural problems in their use.

1. Islatravir and M184V: An Important Condition for Single-Agent PrEP

One of the most important presentations at the session was the preclinical study of the islatravir (MK-8591) implant.

At plasma concentrations considered clinically relevant (~1–4 nM), biodegradable islatravir implants provided full protection against repeated rectal exposure to wild-type SHIV (simian-human immunodeficiency virus). However, protection was significantly weakened when the animals were challenged with SHIV carrying the M184V mutation.

Key results:

• In vitro, there was a 10–20 fold reduction in drug susceptibility with M184V.
• Most animals became infected with the resistant SHIV strain.
• The difference compared to wild-type protection was statistically significant.
• Plasma and peripheral blood mononuclear cell drug levels were similar in both challenge groups.

Importantly, the failure to protect was not due to insufficient drug concentration. The same concentrations that protected against wild-type virus were ineffective against the virus with M184V — indicating that the issue is not dosage adequacy but a shift in pharmacodynamic targets.

QUESTIONS

During the discussion, one participant asked directly:

“If drug levels fall to the lower end of the protective range, will protection against virus with the M184V mutation be lost first?”

The presenter replied:

“The preventive threshold we use is based on wild-type virus. We do not yet know what that threshold will be for resistant variants.”

Another participant questioned the real-world relevance:

“In real transmission, viruses with M184V have reduced fitness. How does this challenge model reflect that ecological balance?”

Researchers acknowledged that differences in fitness make interpretation difficult but noted that resistant variants still transmit and circulate among treated populations.

Key conclusion:

Single-agent long-acting strategies with NRTTIs should consider pharmacodynamic thresholds adjusted for resistance, not only suppression of wild-type virus.

2. MK-8527: Monthly Oral PrEP and Quantitative Evaluation

The presentation on MK-8527 showed a different type of progress — less striking biologically but strategically important.

Using integrated population pharmacokinetic modeling based on multiple Phase 1 and Phase 2 studies, scientists selected a dose of 11 mg once a month for Phase 3 trials.

The choice was based on maintaining intracellular MK-8527 triphosphate (MK-8527-TP) above 0.03 pmol/10^6 PBMC, a preventive efficacy threshold derived from preclinical modeling and early human dose–response relationships.

Investigators emphasized the depth of the modeling:

- A five-compartment pharmacokinetic model

- Body weight included as a covariate

- No significant effects of sex or age

- Protective concentrations predicted at Day 31

- Protective exposures maintained through Day 38

- Adequate exposure predicted in pregnancy

QUESTIONS

One audience member focused on onset kinetics:

“If intracellular levels rise so quickly, could lower doses sustain efficacy in an event-driven approach?”

Answer:

“Current development focuses on maintaining stable monthly concentrations. Alternative strategies will require further evaluation.”

In light of the earlier islatravir discussion, resistance was also raised:

“How confident can we be that the preventive threshold holds in the presence of resistance mutations?”

Investigators acknowledged that resistance-adjusted modeling has not yet been fully developed.

Thus, MK-8527 occupies an intermediate position:

• Less invasive than injectable PrEP
• More stable adherence than daily oral regimens
• Potentially scalable in resource-limited settings
• Success dependent on how robust the pharmacokinetic threshold is across real-world viral diversity

3. ANRS Prévenir: Proof of PrEP Efficacy and Its Limits

The Prévenir cohort provided one of the most compelling long-term PrEP datasets shown at CROI in recent years.

Key findings:

- Over 13,000 person-years of follow-up

- Overall HIV incidence: 0.11 per 100 person-years

- No difference between daily and event-driven dosing

- Equivalence of event-driven PrEP over a median of nearly four years is now beyond doubt

But the most significant moment came from the epidemiological analysis comparing regional diagnoses in 2015–2016 versus 2023–2024:

• –33% among MSM born in France
• +73% among MSM born abroad
• +95% among transgender women

QUESTIONS

An epidemiologist in the audience asked:

“Can the regional decline be explained by the study itself, or are we observing broader long-term trends?”

Professor Molina responded:

“The study was not designed solely to assess efficacy, but also to promote PrEP uptake. We believe it contributed — but obviously not in all population groups.”

Another question addressed structural inequality:

“Are we protecting only those who already have access to care?”

The conclusion was clear. Biologically, PrEP worked. However, it did not transform the system everywhere.

Behavioral data further confirmed biological effectiveness: unprotected anal sex increased during follow-up, yet HIV incidence remained very low. Still, hepatitis C incidence (0.46 per 100 person-years) and high STI rates indicate persistent syndemic risk patterns.

4. PURPOSE 1: Lenacapavir in Cisgender Women — Near-Complete Protection

PURPOSE 1 remains one of the most important PrEP studies globally.

In the updated analysis of the randomized, blinded phase:

• 2 HIV cases among 2,134 participants receiving lenacapavir
• Incidence: 0.07 per 100 person-years
• Much higher incidence in oral comparator arms

Detailed analysis of breakthrough cases was presented:

Participant C:

- Received injections on schedule

- Diagnosis at Week 65

- Lenacapavir level at diagnosis: 44.6 ng/mL

- Inhibitory quotient (IQ4) above the target

This raised a critical question:

“How can infection occur at therapeutic drug levels?”

Researchers noted that the explanation remains under investigation, with potential hypotheses:

1. Infection closer to the end of the dosing interval
2. Viral load exceeding pharmacologic limits
3. Local tissue variability not reflected in plasma levels

Participant D:

- Missed injection at Week 52

- Diagnosis about 487 days after last injection

- Lenacapavir level at diagnosis: 0.65 ng/mL (below threshold)

QUESTIONS

One listener asked:

“Are there demographic or biological predictors of breakthrough infections?”

Answer:

“At this stage, no consistent distinguishing features have been identified.”

There was also discussion of community perceptions:

“How do participants react to rare breakthrough infections?”

Response:

“Acceptability remains high. The efficacy profile is still exceptional.”

5. PURPOSE 2: Lenacapavir in MSM and Gender-Diverse Individuals

Updated data showed:

• 2 HIV cases in the lenacapavir arm during primary analysis
• Additional cases during extended follow-up
• 12 cases in the daily oral TDF/FTC arm

Conclusions remained unchanged: lenacapavir provides substantially greater protection than daily oral PrEP. Breakthrough analyses again focused on pharmacokinetics and adherence. No clear new resistance profiles have yet emerged, but monitoring continues.

Unified Scientific Message

Across all five presentations, a clear hierarchy of prevention strategies emerged:

• Twice-yearly injectable lenacapavir: highest efficacy
• Monthly oral MK-8527: promising flexible alternative
• Daily and event-driven TDF/FTC: proven, sustainable, scalable
• Single-agent NRTTI strategies: sensitive to resistance

CROI 2026 demonstrated that pharmacologic prevention is no longer the limiting factor in the fight against HIV. Instead, the key limiting factors are:

- Resistance ecology

- Adherence to dosing intervals

- Structural inequality in drug access

- Population coverage

As one leading prevention researcher noted after the session:

“The biological problem is nearly solved. What remains is the problem of distribution — of medicines, of access, and of trust.”

The opening set the main tone for the conference — this will be an intensive dialogue about the future of HIV treatment and prevention, as well as defending scientific research in a changing political environment.

The Life4me+ team, as always, is present at CROI and is covering the main news.

More than 3000 scientists, clinicians, and activists from 65 countries are taking part in the conference. Notably, 22% of them are attending CROI for the first time.

This year, the organizers accepted 958 general abstracts out of 1594 submissions. The program includes 98 oral presentations and 930 poster sessions. Also this year, CROI introduced structural changes, including the elimination of daily press conferences.

Opening Plenary Session

The opening plenary session was devoted to three fundamental directions that define the modern agenda.

• 30 Years on the Path to an HIV Cure

Professor Sharon Lewin from the University of Melbourne reminded the audience that scientists have been searching for a way to completely cure HIV for 30 years. Despite enormous progress in understanding viral reservoirs and immune control, she said, finding a final solution to the problem requires long-term investment and international cooperation.

• Science Under Political Pressure

Activist Peter Staley raised an important issue: science increasingly faces political pressure. He called for renewed resistance and efforts aimed at protecting policy based on factual evidence.

• Prevention as Partnership

Representing the South African Desmond Tutu HIV Foundation, Linda-Gail Bekker spoke about prevention. In her view, medications are only half of success — the other half is trust and respect for the people we want to help.

Lifetime Achievement Award

But the most touching moment was the presentation of the first-ever CROI Lifetime Achievement Award. It was given to Carl Dieffenbach for his leadership as Director of DAIDS and for being “a kind, tireless, compassionate, often underappreciated champion.”

In his acceptance speech, he said something important:

“HIV will not disappear if it is brought under control in only one country.”

And that means the work to fight the epidemic continues.

However, the study also raises a big question: Are doctors using the right tests to find out who needs these drugs the most?

Dr. Steven Grinspoon and his team at Massachusetts General Hospital found that a certain type of hidden artery plaque—called non-calcified plaque (NCP)—might be a better warning sign for heart disease in people with HIV than the standard test that looks for hardened (calcified) plaque.

This finding could change how doctors decide who should take statins and help more people get the treatment they need before a serious heart problem occurs.

What Did the Study Find?

Researchers followed 804 people with HIV for nearly six years, tracking their plaque levels, inflammation, and early signs of heart damage. Here’s what they found:

• 40% of participants already had soft (non-calcified) plaque in their arteries.
• People with this plaque were more likely to have serious heart problems later.
• Inflammation markers, such as hs-CRP and IL-6, were linked to higher heart risk.
• Pitavastatin (a type of statin) worked best in people who already had this soft plaque or early signs of heart injury.

This means that people with HIV who already have early signs of heart disease may benefit the most from taking statins.

Are Doctors Using the Right Test?

In the general population, doctors often use a coronary artery calcium (CAC) scan to decide who needs statins. This test looks for hardened plaque—the kind that builds up over time and increases the risk of heart attacks.

But at the CROI 2025 conference, Dr. Laura Waters from NHS London asked a key question:

“If I understand correctly, coronary calcium should not be used to decide if people with HIV need statins. In the US, calcium scans are used to help determine who should take them. For people with HIV, you’re saying that soft, non-calcified plaque may be more important. Is that right?”

Dr. Grinspoon confirmed that while CAC scans are useful in the general population, they may not work as well for people with HIV:

“There’s a higher amount of non-calcified plaque in people with HIV. Coronary calcium does predict heart disease, but not as strongly as non-calcified plaque does in this group.”

In other words, the usual test might miss many people with HIV who are actually at high risk.

He also emphasized that anyone with a heart disease risk over 5% should consider statins—regardless of what a calcium scan shows (Grinspoon et al., CROI 2025).

What This Means for People with HIV?

1. Statins help – The REPRIEVE trial confirms that statins lower heart disease risk in people with HIV (Grinspoon et al., 2023).
2. Some people benefit more – Those who already have soft plaque or inflammation may get the biggest benefit from statins.
3. Doctors may need to change how they assess risk – Instead of just using calcium scans, they may need to look at soft plaque and inflammation levels in people with HIV.

The Bottom Line

If you have HIV, keeping your heart healthy is just as important as managing your HIV virus.

This study shows that statins can protect against heart attacks and strokes, even in people who don’t yet have symptoms.

If your doctor talks about checking your heart health, ask about soft plaque and inflammation markers in addition to a calcium scan. The REPRIEVE trial has made one thing clear: statins can make a real difference in protecting the hearts of people with HIV—if we make sure they’re given to the right people.

A Step Forward: The EMBRACE Study

Last year, researchers tested N6LS in the BANNER study, showing it worked well as a standalone treatment for people new to HIV medication. Now, the latest EMBRACE study is taking it further, by combining N6LS with another long-acting treatment, cabotegravir (CAB LA), to see if it can help people maintain viral suppression with just a few doses per year.

How the Study Worked

The study involved 125 people across the U.S. and Puerto Rico, all of whom had their HIV under control before joining. Participants were divided into three groups:

• N6LS (intravenous) + CAB LA (injections every four months) – 96% stayed undetectable.
• N6LS (under-the-skin) + CAB LA (subcutaneous injections every four months) – 94% stayed undetectable.
• Standard daily HIV pills – 100% stayed undetectable.

While a small percentage experienced a return of the virus, no one developed drug resistance, which is crucial for keeping future treatment options open.

What About Side Effects?

The treatment was generally well tolerated, but how it was given made a difference:

• Intravenous injections (directly into the vein) caused fewer side effects.
• Subcutaneous injections (under the skin) led to injection site reactions in some people, lasting about a week.
• Three people withdrew due to side effects, but there were no serious complications.

Looking Ahead: The Future of Long-Acting HIV Treatment

During the study presentation, experts raised key questions about the treatment’s future. One asked why CAB LA was given monthly instead of every two months. Researchers explained they are taking a step-by-step approach,and plans to test six-month dosing for N6LS and two-month dosing for CAB LA in future studies. Another question was about how many people with HIV could benefit from N6LS?, Rand researchers estimated about 72% of patients would be eligible.

Why This Matters

The idea of getting just a few injections a year instead of taking daily pills could be life-changing for many people living with HIV. While this study shows promise, there’s still work to do in refining the treatment and making it even more convenient. Future research will focus on longer-lasting doses and ensuring the best possible outcomes for patients.

Key Takeaways

• Scientists are working on HIV treatments that require fewer doses per year.
• The EMBRACE study builds on earlier research and tests N6LS combined with CAB LA.
• Most participants remained undetectable, though daily pills were slightly more effective.
• Intravenous injections had fewer side effects than under the skin injections.
• Future studies will explore even longer gaps between doses.

This research marks an exciting step toward making HIV treatment easier and less of a daily burden for millions of people worldwide.

The studies, conducted by Merck & Co., Inc., suggest that switching to this new combination therapy is as effective as continuing with existing treatment regimens.

Why This Study Matters

For people living with HIV, maintaining an undetectable viral load is crucial for staying healthy and preventing the transmission of the virus. Many individuals currently take combination antiretroviral therapy (ART), which involves multiple medications. This new research indicates that switching to the once-daily DOR/ISL pill could provide a simpler, equally effective alternative.

Understanding the Studies

Researchers conducted two separate trials to evaluate the effectiveness and safety of switching to DOR/ISL:

1. The First Study: Included 513 participants who were already using Biktarvy (BIC/FTC/TAF), one of the most commonly prescribed single-tablet HIV treatments. This study specifically evaluated switching from this widely used standard regimen. Of these, 342 switched to DOR/ISL (100/0.25 mg), while 171 continued BIC/FTC/TAF.

2. The Second Study: Included 551 participants who were taking a variety of other oral ART regimens, covering all other standard HIV treatment combinations. This study evaluated switching from a broader range of treatment regimens. In this study, 366 switched to DOR/ISL (100/0.25 mg), while 185 continued their baseline ART.

In both studies, participants were randomly assigned to either continue their current treatment or switch to DOR/ISL. Scientists then measured whether the new treatment could keep their viral load suppressed after 48 weeks.

Key Findings

• In the first study, 91.5% of those who switched to DOR/ISL maintained an undetectable viral load, compared to 94.2% of those who continued their existing regimen.
• In the second study, 95.6% of those who switched to DOR/ISL remained undetectable, compared to 91.9% of those who stayed on their previous ART.
• Very few participants (less than 2%) experienced an increase in viral load after switching, showing that DOR/ISL was just as effective as other standard treatments.

What About Side Effects?

Both studies found that DOR/ISL was well tolerated, with side effects similar to existing HIV treatments. The most common issues were mild, including headaches, diarrhea, and fatigue. Serious side effects were rare, and only a small percentage of participants discontinued the new treatment due to adverse effects.

A Step Toward Simpler HIV Treatment

These results are promising for individuals who want a convenient, once-daily pill without compromising effectiveness. A simpler treatment regimen could improve adherence, making it easier for people to stay on their medication and maintain their health.

While further research and regulatory approvals are needed before DOR/ISL becomes widely available, these findings mark an important step toward more accessible and manageable HIV treatment options. If approved, this therapy could provide a new alternative for people living with HIV, seeking a simpler and equally effective regimen.

What’s Next?

Scientists will continue monitoring participants, to ensure long-term effectiveness and safety. If these positive results hold, DOR/ISL could become a key option in the evolving landscape of HIV treatment, offering hope for even more streamlined and effective care in the future.

A new study conducted in Africa suggests that long-acting injectable HIV treatment could be just as effective as daily pills—and might offer a new way forward in the fight against HIV.

Long-acting injectable therapy (LA) has become a recommended alternative to oral antiretroviral therapy (ART) for HIV-1 treatment in high-income countries. However, its role in treatment programs in Africa remained uncertain due to differences in demographic factors, viral characteristics, and healthcare infrastructure. To address this gap, the ongoing phase 3b randomized CARES trial was designed to evaluate the efficacy, safety, and tolerability of switching from oral ART to LA therapy in African settings.

The CARES trial, conducted across eight sites in Uganda, Kenya, and South Africa, studied whether long-acting injections of two drugs—cabotegravir (CAB) and rilpivirine (RPV)—could match the effectiveness of traditional daily oral antiretroviral therapy (ART).

A year ago, at the Conference on Retroviruses and Opportunistic Infections (CROI 2024), researchers presented the 48-week results, showing that the injectable treatment was non-inferior to daily pills. Now, at CROI 2025, new 96-week data confirms that long-acting injectables remain highly effective over time, reinforcing their potential as an alternative to daily ART in sub-Saharan Africa.

What the Study Found

The trial included 512 adults with HIV who had already achieved stable virus control on daily pills. They were randomly assigned to either continue with their oral medication or switch to the long-acting injection, which was administered intramuscularly every eight weeks.

After 96 weeks—almost two years—researchers found that 96.9% of people receiving the injections had successfully maintained very low levels of the virus in their blood (defined as <50 copies/mL). That figure was nearly identical to the 97.3% success rate in those taking daily pills. The study also confirmed non-inferiority, meaning the injectable treatment was not worse than the oral therapy within a predefined margin (−0.4%; 95% confidence interval: −3.1 to 2.0%).

These findings build upon the 48-week results, which also demonstrated comparable efficacy between injectables and daily ART. The long-term durability of this treatment approach suggests it could be integrated into HIV care programs with confidence.

Why this Matters

While daily pills have revolutionized HIV treatment over the years, they come with challenges. Some people struggle to take medication every day due to stigma, forgetfulness, or personal circumstances. Missing doses can increase the risk of the virus developing resistance to medication.

Long-acting injectables could provide a more convenient alternative, especially for people who have difficulty maintaining a daily pill routine. This could be particularly important in regions where access to consistent healthcare is a challenge.

Dr. Cissy Kityo, one of the lead researchers on the study, emphasized that the injections could be a “game-changer” for HIV treatment programs, particularly in Africa, where healthcare access varies and long-term adherence to daily pills can be difficult for many patients.

Are there Any Risks?

Like any medical treatment, the long-acting injection had some side effects. About 16% of participants receiving the injections experienced moderate to severe side effects, compared to 9% in the group taking oral pills. The most common issue was injection-site reactions, such as pain, swelling, or abscess formation, though these were generally mild to moderate in severity.

A small number of people on the injectable treatment—1.6%—experienced what’s known as confirmed virologic failure (CVF), meaning their virus levels increased beyond 200 copies/mL despite the treatment. However, three of these four participants were able to regain viral suppression after switching to a regimen of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and dolutegravir (DTG). Notably, baseline resistance mutations to rilpivirine were detected in 8% of participants, though these did not appear to significantly impact treatment success rates.

What’s Next?

The study’s findings suggest that long-acting injectable HIV treatment is a safe and effective alternative to daily pills. However, questions remain about how best to implement this approach in healthcare systems across Africa and beyond.

One challenge is ensuring that patients return for their injections every eight weeks. Unlike pills that can be taken at home, injectables require visits to a healthcare provider. Infrastructure improvements, expanded access to healthcare facilities and patient education, will be key to making this treatment widely accessible.

The potential benefits are significant. If scaled up, long-acting injections could reduce the burden of daily pill-taking, help overcome stigma, and improve overall HIV treatment outcomes.

As more studies confirm these findings, countries around the world may soon consider adding long-acting injectable therapy to their HIV treatment programs. For millions of people living with HIV, this could be a major step toward simpler, more effective care.

What if one shot, once a year, could provide the same protection?

That future is now within reach. Scientists at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025 presented new research showing that a single yearly injection of lenacapavir (LEN) could be just as effective as current methods—potentially revolutionizing HIV prevention.

Why a Yearly Shot Could Be a Game-Changer

PrEP (pre-exposure prophylaxis) has dramatically reduced HIV transmission, but many people struggle to take a pill every day or get regular injections. A once-a-year shot could remove these barriers, making it easier for more people to stay protected.

Current PrEP injections, which are given every six months, have already been shown to work incredibly well. In a recent study of women using this method, not a single participant contracted HIV. But researchers wondered: could we go even longer between doses?

What the New Study Found

Scientists tested two different formulations of a single, high-dose injection of LEN to see if it could last for a full year. Participants received their shot, and then researchers tracked how the drug remained in their bloodstream over time.

The results were very promising:

• The drug stayed at protective levels for an entire year, meaning one shot could be enough to keep someone safe from HIV for 12 months.
• It was safe and well tolerated, with the most common side effect being mild pain at the injection site, which typically went away within a few days.
• Using an ice pack before the injection significantly reduced discomfort, making the process easier for participants.

What This Means for the Future of HIV Prevention

If this yearly injection proves successful in larger studies, it could transform how we approach HIV prevention. Instead of taking a daily pill or getting two shots a year, people could simply visit their doctor once a year for a single injection—and stay protected for the next 12 months.

For people who face stigma, struggle with healthcare access, or simply find it hard to remember to take a pill, this could be life-changing. It would also make HIV prevention efforts more effective on a global scale, especially in communities where daily medication isn’t a realistic option.

What’s Next?

The next step is a larger trial to confirm these findings in a diverse group of people at risk of HIV. If that trial goes well, this once-a-year shot could become a reality—giving millions of people an easier, more effective way to stay safe.

For now, the scientific community is excited. A future where HIV prevention is as simple as an annual doctor’s visit may soon be within reach.

A new Phase 2 study, presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025, suggests this may soon become a reality.

Researchers from Yale University and other institutions have been investigating a novel combination therapy involving lenacapavir (LEN), a long-acting HIV capsid inhibitor, and two broadly neutralizing antibodies (bNAbs), teropavimab (TAB) and zinlirvimab (ZAB). The study evaluates whether these six-monthly (Q6M) injections could effectively replace daily oral antiretroviral therapy (ART).

This research builds on previous results from the Phase 1b study, which were presented at CROI 2024 in Denver. That earlier trial demonstrated the LEN+TAB+ZAB combination successfully maintained virologic suppression for six months in 18 out of 20 participants. The current Phase 2 study expands on these findings with a larger participant group and a more rigorous assessment of safety and efficacy.

Why This Matters

Adherence to HIV medication remains one of the biggest challenges in long-term treatment. Missing doses can lead to drug resistance and loss of viral suppression. A long-acting injectable regimen could be a game-changer, particularly for individuals who struggle with daily pill regimens, due to stigma, lifestyle, or personal preference.

The Study

The trial enrolled 80 participants, all of whom had maintained undetectable viral loads for at least a year on standard oral ART. The participantswererandomlyassignedintotwogroups:

• 53 participants switched to the injectable regimen (LEN+TAB+ZAB) every six months.
• 27 participants continued their stable oral therapy.

The primary goal was to determine whether those on the injectable regimen maintained viral suppression at week 26, a key milestone for treatment efficacy.

Key Findings

• 96% of participants receiving the injectable combination maintained viral suppression, a rate comparable to those who remained on oral ART.
• Only one participant in the injectable group experienced viral rebound (HIV-1 RNA ≥50 copies/mL).
• No serious side effects or discontinuations due to adverse reactions were reported.
• The most common side effect in the injectable group was mild injection site reactions, such as pain or swelling—similar to other injectable HIV treatments.
• Importantly, no infusion-related reactions occurred with the antibodies TAB and ZAB.

A Step Toward the Future

The results support further exploration of this twice-yearly treatment, as a viable alternative to daily pills. If confirmed in larger trials, this could revolutionize HIV care, making treatment more convenient, discreet and accessible for millions of people worldwide.

The next phase of research will assess long-term efficacy and safety beyond the 26-week mark, with a full year of follow-up data expected soon.

For now, the findings provide hope for a new option in the fight against HIV—one that could offer greater freedom and flexibility for those living with the virus.

Organized by the San Francisco AIDS Foundation’s HIV Advocacy Network (HAN) alongside researchers attending the Conference on Retroviruses and Opportunistic Infections (CROI). The event featured passionate speeches and urgent calls to action. The crowd, filled with activists and medical professionals, repeatedly chanted: “Research is resistance! Science is survival!” as speakers emphasized the importance of continued investment in HIV research.

“Science Saved My Life”

Lauren Thomas from the San Francisco AIDS Foundation opened the rally with an enthusiastic welcome to the crowd. She introduced Vince Crisostomo, a longtime HIV activist who was diagnosed in 1989 and told he wouldn’t live past 30.

“Last month, I turned 64,” Crisostomo said, drawing cheers from the audience. “Science saved my life. We cannot let them take that away from future generations.”

His speech was a reminder of how far HIV treatment has come, but also a warning: Without continued funding, many of the advances that have transformed HIV from a death sentence into a manageable condition, could be lost.

The Threat to HIV Research

The rally was a response to proposed federal budget cuts that could freeze funding for critical HIV research. Programs under threat include the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the President’s Emergency Plan for AIDS Relief (PEPFAR)—all of which play crucial roles in preventing, treating, and researching HIV worldwide.

Dr. Tyler TerMeer, CEO of the San Francisco AIDS Foundation, stressed the high stakes:

“If we let politics take priority over science, we risk losing decades of progress,” he said. “We are standing up not just for research, but for the people whose lives depend on it.”

Beyond HIV: How Research Benefits Everyone

Speakers also highlighted how HIV research has led to major medical advancements beyond the virus itself, including breakthroughs in cancer treatment, hepatitis therapy, and even the rapid development of COVID-19 vaccines.

Dr. Steve Deeks, a professor at UCSF, explained, “The COVID-19 vaccine was made possible by HIV researchers. Treatments for hepatitis C and tuberculosis? Also thanks to HIV research. Cutting funding now would hurt medical progress for everyone.”

Dr. Beatriz Grinsztejn, president of the International AIDS Society, warned of global consequences. “Millions still don’t have access to life-saving HIV treatment,” she said. “If these cuts happen, we could see a resurgence of the epidemic.”

A Personal Fight

For many in the crowd, the issue was deeply personal. Naina Khanna, director of the Positive Women’s Network-USA, spoke about how these cuts would disproportionately affect marginalized communities.

“This isn’t just about science—it’s about justice,” she said. “These cuts are a death sentence for Black and brown people, for trans people, for those already pushed to the margins.”

A Movement That Won’t Back Down

Despite the serious concerns, the rally was filled with energy and determination. Activists led the crowd in chants of “Act up! Fight back!”, a battle cry from the early days of HIV/AIDS activism.

Dr. Franco Chevalier, an infectious disease specialist, left the crowd with a powerful message: “We are not just researchers. We are fighters. We are not going anywhere.”

As the rally came to a close, attendees remained engaged, many vowing to continue pressuring lawmakers to protect HIV research funding.

For those who were unable to attend, organizers encouraged people to call their congressional representatives and demand action.

“Science saves lives,” TerMeer reminded the crowd. “We’re not letting anyone take that away.”

A Potential Alternative to Daily HIV Medications

For decades, daily ART has been the gold standard for managing HIV, preventing the virus from replicating and allowing people with HIV to live long and healthy lives. ART requires strict adherence, as missing doses can lead to viral rebound and drug resistance. Scientists have long searched for alternative strategies that could offer people with HIV greater flexibility in managing their treatment.

The RIO study tested whether two bNAbs — 3BNC117-LS and 10-1074-LS — could help maintain viral suppression in people with early-treated HIV, after stopping ART. While some studies are evaluating bNAbs in combination with long-acting antivirals for HIV treatment, RIO focused on their potential role in post-treatment viral control as part of an HIV cure strategy.

The trial enrolled 68 participants, all of whom had begun ART soon after their diagnosis and had well-controlled viral loads. Participants were randomly assigned to receive either:

• Two doses of the bNAb combination, administered intravenously over several months, or
• A placebo, with no active treatment.

After receiving their assigned treatment, all participants stopped taking ART to evaluate whether the antibodies could keep the virus in check.

Findings: A Longer Period Off ART for Many

The study results were striking. By 20 weeks after stopping ART,

• 75% of those who received the antibodies had not experienced viral rebound, compared to just 9% in the placebo group.
• Some participants remained off ART for over a year, with 21% still controlling the virus at 72 weeks.
• Six participants in the bNAb group showed no viral rebound even after their last dose of antibodies.

Dr. Sarah Fidler, who led the study, emphasized the potential impact of these findings:

“What we see is a strong delay in viral rebound among those receiving bNAbs. The data suggests that in some cases, the antibodies may help the immune system control the virus more effectively, extending the time people can remain off ART.”

Although not a cure itself, this study supports ongoing efforts to develop strategies for functional HIV remission—where the virus remains controlled without the need for daily ART.

Could This Be Used Worldwide?

One of the biggest questions surrounding this approach is whether it could be used globally, including in lower-income settings, such as sub-Saharan Africa, where the burden of HIV remains high.

Dr. Fidler acknowledged that while bNAb-based immunotherapy is not yet ready for widespread use, there is reason to be optimistic.

“If we find the right combination of antibodies, matching a person’s specific strain of HIV, this could be much more feasible to roll out. A large study in South Africa tested similar antibodies for HIV prevention and showed they can be delivered in different settings. We’re not quite there yet, but the potential is very exciting.”

If successful, this approach could reduce reliance on daily ART, making HIV treatment and remission strategies more accessible to people who face challenges with lifelong medication adherence.

Safety and Future Considerations

The study also found that the treatment was safe and well-tolerated:

• Nine serious adverse events were reported, including one death, but none were linked to the study treatment.
• 94% of those who restarted ART regained full viral suppression within 12 weeks.
• No immune rejection of the antibodies was detected.

Experts at the conference raised important questions about the long-term feasibility of bNAbs. Dr. Laura Waters, a leading HIV researcher with the NHS in London, asked whether people with underlying health conditions should have been included in the study.

Dr. Fidler acknowledged the concern:

“We excluded individuals with major comorbidities, but future studies will need to look at how bNAbs interact with other health conditions. Biomarkers like IL-6 and CRP, which indicate inflammation, may help guide treatment decisions.”

Another critical question concerned how the virus rebounded in participants. A researcher asked whether the pattern of rebound differed between the placebo group and those who received bNAbs.

Dr. Fidler explained that the placebo group rebounded quickly and at high levels, leading most participants to restart ART immediately.

“In contrast, those receiving bNAbs had a much slower and more controlled rebound, with some staying undetectable for much longer,” she noted.

A Step Toward Long-Term HIV Remission?

The study’s findings raise broader questions about the potential role of bNAbs in HIV cure research. Could this approach eventually replace daily ART for some individuals?

One of the key questions raised at CROI was whether bNAbs are preventing viral rebound primarily through direct action against HIV, or whether they are also boosting the body’s own immune response.

Dr. Fidler acknowledged that it’s likely to be a combination of both factors:

“We are still analyzing the immune data, but we see hints that bNAbs may be enhancing HIV-specific T-cell responses, which could help explain why some people remain off ART longer.”

However, there are still hurdles to overcome. Resistance to bNAbs remains a challenge, and researchers are still working to determine how many people could benefit from this approach.

What’s Next?

While the the RIO study provides important insights into HIV cure strategies, additional research is needed to determine:

• How long bNAbs can keep the virus suppressed
• Whether this approach could work for a broader group of people, including those with underlying health conditions
• How to prevent resistance to bNAbs over time

Future studies may explore whether combining different bNAbs or adding immune-boosting therapies could extend viral suppression even further.

For now, the results of the RIO study represent a promising step forward in HIV cure research, offering valuable data on how bNAbs might be used to help people control HIV without daily medication. While ART remains the most effective strategy for managing HIV, these findings suggest that for some, long-acting antibodies could contribute to functional cure strategies—bringing us closer to a future with more treatment and remission options.

A Global Gathering of Experts

This year’s CROI boasts 3,772 registered attendees from 69 countries, with 40% of participants from outside the U.S.. The conference continues its tradition of fostering global collaboration, providing a platform for scientific exchange and the translation of research into public health impact. Notably, 24% of attendees are first-time participants, demonstrating the conference’s commitment to engaging new voices in the fight against HIV.

Key Themes and Opening Messages

During the opening plenary session, the CROI Foundation emphasized its mission to support scientific dialogue, investments in public health, and the translation of research findings into practice. However, it also condemned the censorship of science, targeting of researchers, and withdrawal of funding from critical research and evidence-based treatment programs.

A presentation on the impact of policy changes on HIV incidence highlighted the risks of scaling back prevention efforts. Modeling data presented by Andrew Phillips (UCL) projected a sharp increase in HIV incidence should access to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) be reduced.

Scientific Rigor and Scholarship Support

The conference saw a strong engagement in research, with 1,875 general abstracts submitted, of which 1,076 were accepted. Additionally, 94 late-breaking abstracts and 105 oral abstracts will be presented, along with over 1,000 posters covering cutting-edge discoveries.

CROI 2025 continues to support the next generation of researchers and educators, awarding 311 scholarships to new investigators, 55 to international scholars, and 22 to community educators and mentors.

Response to U.S. Federal Policies

One of the most anticipated discussions centered on how CROI is addressing recent U.S. federal policies affecting scientific discourse. As an independent, foundation-supported conference, CROI has taken measures to ensure inclusivity and participation, including allowing virtual presentations for federal employees facing policy-related restrictions.

Looking Ahead

As CROI 2025 unfolds, attendees will dive into sessions covering new treatment strategies, vaccine developments, cure research, and the intersection of HIV with other infectious diseases. With a strong commitment to scientific integrity and public health impact, this year’s conference aims to set the stage for the next wave of advances in HIV prevention, treatment, and policy advocacy.

The discussions initiated here in San Francisco—a city with a deep history in the fight against HIV/AIDS—will shape the global response to HIV for years to come.

A recent milestone was reached with the first symposium, hosted by the University Hospital of Zurich in partnership with Life4me+ on January 19, 2023, in Switzerland. This pioneering event brought together more than 100 physicians, study nurses, healthcare professionals, patient organization representatives, and people living with HIV.

The upcoming symposium will continue this dialogue between healthcare professionals and community representatives. Led by HIV Professor Jürgen Rockstroh of Bonn, Germany, the event will highlight the challenges and opportunities associated with aging while living with HIV and explore strategies to better engage patients and the public in clinical research.

Harriet Langanke, founder of GSSG, will moderate the discussions among stakeholders and explore their diverse needs and expectations. This symposium provides a unique platform for an open exchange of ideas that has the potential to shape the future landscape of HIV care.

The event is free of charge to all and offers the added benefit of continuing medical education (CME) credits. Those interested in attending can secure their place by registering now.

The accessibility of the symposium is further enhanced by the support of the pharmaceutical companies ViiV, Gilead, and Janssen. Notably, these companies have no influence on the Symposium program, ensuring unbiased discussions focused on the needs of the community.

For full details, including the event program and other information, please download the invitation.

Join us at the Symposium and be a part of shaping the future!

The event program combines theoretical sessions, discussions, interactive and practical workshops. We will explore the topics of relationships, sex, gender and sexuality. We will explore our relationship to the body, learn what the culture of consent is, learn how to identify cyber-bullying and how to protect ourselves from it.

A lot of attention will be paid to the topic of leadership, rights, familiarisation with international youth networks and activists from Central Asian countries. At the end of the camp, those interested will be able to become part of the youth movement and continue to develop in activism.

Who can participate?

Young people of all genders from 18 to 27 years old from Ukraine, located in the territory of the European Union. Also, there are several places for those who are willing to travel from Ukraine on their own.

Everyone can apply for participation, regardless of positive or negative HIV status. The main selection criterion is motivation and ideas on how you can share your experience and knowledge with your peers. Take the time to fill in the application form up until 27 August 2023 inclusive.

To do so, you can follow the link or scan the QR code below.

To find out how the 2022 Summer Camp went - watch the video on our YouTube channel and read about it on the website.

Participation in the camp is free of charge. All travel and accommodation costs are covered by Life4me+. If you have any questions, please contact us on social media and by email: contact@life4me.plus.

"Stay on ART" provides navigation to facilitate access to treatment for people living with HIV, who are resident abroad.

Moving to another country or temporary labor migration is not necessarily easy and presents many challenges. One of them is to make sure you are able to continue taking care of your health. The "Stay on ART" project provides answers to the most frequently asked questions, based on experience and thousands of requests.

• Is it possible to carry antiretroviral therapy with you?

• How and where to get ART?

• Is it possible to buy treatment in pharmacies?

• Where to go for support in emergency situations?

On the project website www.stayonart.com it provides step-by-step algorithms for obtaining medical care and ART, brief instructions for completing the necessary documents, useful links and contacts for public organizations ready to provide assistance.

The geography of the project covers 53 countries of the WHO European Region. Currently, the site contains data on 12 countries: Armenia, United Kingdom, Germany, Georgia, Kazakhstan, Kyrgyzstan, Poland, Russia, Serbia, Slovenia, Montenegro and Switzerland. The information is translated to 6 languages: English, French, Arabic, Russian, Serbian and Ukrainian. Over time, the list will be expanded and data will be updated to reflect geo-political and legislative changes.

If you are travelling to a country where information is contradictory or not readily available, follow these guidelines wherever possible.

• Study the available information in the context of HIV for the country you are going to.

• Aim to take at least a 3-months supply of treatment with you

• Start gathering information and documents as soon as you arrive: the process of applying for and receiving ART can take a long time.  

• Try to find local community organizations and contact them for information and support.

In 2022, Life4me+ helped more than 500 people living with HIV to receive ART and medical care in a new country. With the help of "Stay on ART" we hope to reach tens and hundreds of times more people. And to achieve this goal, we need your support. If you are a doctor, share this information among patients, if you are from the community, spread the word in social networks, personal blogs and groups, if you represent a public organization, become our partner.

It was important for us to unite Ukrainian youth, who’ve been scattered across the European Union since February 2022, and create a safe platform for mutual support, co-operation and communication. Most importantly, we wanted to give these young people skills and knowledge that will help hem adapt to life in a foreign country, maintain their treatment adherence, and support their fellow peers living with HIV.

33 participants came to the summer camp, including HIV activists and mothers with children. Seven specialists from Ukraine, Kyrgyzstan and Germany worked with the participants - with a special focus on mental health, sexual and reproductive health, non-confrontational communication and safety. There was, of course, still time for fun.

According to the participants, the five day long camp was “emotionally intense” and “incredibly productive”. Some attendees went home with ideas for a personal blog, another wanted to start a local support group and a team of activists started planning a series of education videos.

Everyone expressed their desire to hold events, such as this camp, on a regular basis - inviting not just people living with HIV, but young people in general. The goal for 2023 is to hold a similar camp, but this time in nature - with group walks and overnight camping in tents.

The Life4me+ team expresses great gratitude to the specialists who helped organize and hold the summer youth camp 2022: Alyona Khlistik, Nikita Progunova, Lyudmila Kolomoets, Aigul Adzhieva, Irina Lesik and Kristina Shapran.

The device is a portable PCR platform with battery power and internet connectivity, which operating in real time can give both the results of HIV presence and viral load figures within 60 minutes.

Truenat runs on existing Truelab infrastructure and does not require additional set-up or equipment. The platform can currently test for 35 diseases, including COVID-19, tuberculosis, hepatitis, HPV, dengue and malaria.

“For any disease, early detection is always the key to stop its spread. HIV was first identified more than 50 years ago, and we don’t have a cure yet. So testing is the first step to preventing the further spread of the disease. We needed an effective means of testing at point-of-care, which is cost-effective and has a short sample-to-result time. We’ve achieved that with Truenat. Truenat HIV1/HIV2 can provide test results in an hour, assuring early and accurate diagnosis of the infection,” Dr. Chandrasekhar Nair, CTO and Director, Molbio Diagnostics.

This new vaccine works in the same way as the mRNA based coronavirus vaccines - your body’s cells “read” the genetic information received in the vaccine and begin producing viral antigens that activate the immune system. Currently, mRNA technology is being used to develop preventative tools for HIV, influenza, malaria and other infections.

In the case of cancer, the mRNA vaccine is therapeutic rather than preventative, it is administered to people to treat existing tumours and/or prevent against relapse. The study showed that this new technology plays well alongside existing treatments.

In the study, the researchers studied ways to increase the immune response by changing the point that the antigens entered the body. mRNA molecules were delivered directly to the lymphatic systems, and not to the liver as was done previously.

Testing on mice have shown that this new mRNA vaccine causes a more powerful immune reaction and, in combination with other therapy, effectively suppresses the tumour. In 40% of cases a complete remission was seen.

Previously, scientists in the United States created a possible cancer vaccine based on viruses and bacteria. The study showed that this combination worked more effectively than treatment with separate agents. Tests conducted on animals showed that vaccination with adenovirus and bacteria significantly reduced the tumour and increased survival rates.

“I naively thought: Everybody knows hormones can affect lots of physiological processes—our metabolism, our heart, our bone density. It must be affecting the immune system,” she says.," says Dr. Sabra Klein of Johns Hopkins University.

In immunology, it has long been believed that gender differences do not matter. Historically, clinical trials have focused on male participants, which has led to serious consequences for public health and medicine. For example, women were more often denied vital HIV treatment, and may have had serious side effects from drugs and vaccines if they received a "male" dose of the drug.

Different diseases affect us in different ways

Studies have shown that men and women suffer from infectious or autoimmune diseases in different ways. And this difference has a biological basis.

Women are nine times more likely to suffer from lupus and have severe asthma. They are also three times more likely than men to suffer from multiple sclerosis.

Meanwhile, men are twice as likely to suffer from tuberculosis than women, and are more likely to die from COVID-19. Experts attribute this to immune responses, as well as sociocultural gender differences: men are more likely to smoke, or work in industries such as mining or construction. This means that they are more likely to be exposed to toxic substances that can weaken the immune protection of the lungs.

Male and female immune systems also respond differently to HIV and some cancer treatments.

Why do women have a stronger immune response?

This phenomenon occurs in many mammals - and there is an evolutionary reason for that. One hypothesis suggests that a stronger immune response in women contributes to the transmission of a larger number of antibodies to children in the womb and through breast milk. However, increased immune reactions that help support infants' lives also increase the risk of autoimmune conditions when women get older.

Differences in the immune system also can manifest themselves on the X chromosome. The TLR7 gene plays an important role in the recognition of pathogens and activation of the immune system, but at the same time it is this gene that contributes to the higher prevalence of autoimmune conditions in women - especially lupus.

The TLR7 gene also contributes to a stronger immune response to HIV. Therefore, many women in the 1990s were left without therapy due to a lower viral load than in men. However, as experts note, it is the immune response, not the viral load, that "is the dominant predictor of the progression of HIV into AIDS."

What about transgender people?

Unfortunately, there are a number of groups of people whose immune system who have hardly been studied. Transgender people belong to this category, despite the fact that they have the highest risk of contracting HIV.

According to experts, hormonal therapy can change a person's immune response, but social factors can lead to increased stress and potentially adversely affect their immune system.

It is reported that immunologists are planning several studies in this area in the near future.

“We need to look at how men and women and gender minorities are impacted differentially so we can have better health care, better medicine, better vaccines,” says Morgan.

Dolutegravir is one of the more modern antiretroviral drugs, and is classified as a BCS-II molecule, which means it has solubility issues.

To increase its solubility and bioavailability, scientists synthesised ‘Chitosan nanoparticles containing DTG using spray drying technology’. The resulting nanoparticles were examined with the possibility of administration orally with milk, or other food products, as a potential paediatric antiretroviral treatment. The tests were conducted on Balb-C mice, and the results compared to pure DTG.

• Based on the results of the study, the research team drew the following conclusions:
• Biodistribution of the drug in plasma and organs was higher (2.5x) when administered as nanoparticles, rather than in its pure form.
• Joint administration of the drug with milk does not affect the absorption rate, but it does increase the time taken to reach maximum concentration.
• The distribution of the active substance in the brain was significantly higher in subjects who were treated with the nanoparticle formulation.
• Tests of organ and blood samples did not show increased toxicity associated with nanoparticle treatment.

The authors of the study believe that DTG nanoparticles can be useful for the treatment of paediatric HIV, especially when combined with milk. This will make treatment easier, and more pleasant, to administer - leading to increased adherence and better outcomes.

Life4me+ participated in this event for the second year running. Read our article, below, about the meeting for children living with HIV and what non-children's problems it raised.

Children tempered by stigma

Children and adolescents often react to a HIV diagnosis calmly, young people tend to favour tolerance and respect individuality. For the most part, problems associated with stigma are created by adults - they fear HIV las they would fire, they still remember these posters from the 90s, which proclaimed that: "AIDS is death!”. Now, children suffer because of this.

After everything that was said, heard and seen at the rally, I want to appeal to everyone:

"Let's make it easier. Children should not suffer. They are not responsible for their parents and for problems in society. Stop kindling stigma. Enough oblique glances, whispers behind our backs and baseless accusations to our faces”

When children are told that they have HIV, they don't feel anything in that moment. HIV is a blank slate for them. There is no stigma, no self-stigma, no fear. All this is layered on later. These "layers" need to be stopped. There are four main things you need to know about HIV:

1. HIV is not transmitted via normal household and daily activities. There are three methods of transmission: sexual, through blood, and from mother to child during pregnancy or childbirth.
2. A person with HIV should always take their treatment as directed by their HIV clinic. This stops the replication of the virus.
3. U=U: people with an undetectable HIV viral load cannot transmit the virus to their sexual partners.
4. People with HIV, who are taking treatment, can have healthy children free of HIV.

These facts have already been repeatedly proven by scientific research that is available in the public domain. If everyone tries to learn at least a little more about HIV, about the scientific progress that has taken place in the last thirty years, there will be less stigma. People have to be kinder. There are no diseases in the world that should allow people to be treated inhumanely.

Uncrying tears

When you look at the artwork that was created during the meeting, it becomes clear WHAT these children have had to face.

There is so much PAIN in the children's art… So many unspoken words…

• I can't say that I have HIV - I can't.
• I can't talk to anyone about it - it won’t be accepted.
• I can't share my feelings - I'm afraid they'll be rejected.
• I can't fight the system - I'll lose.
• I can't be happy - I'm not worthy.

Serious psychological work with children takes place at the meeting. Many people take time to just be able to start talking about their feelings, resentments and fears.

There were a lot of tears. They were every day. And not only children, but adults cried too. In the first days, these were tears of anger, resentment, self-pity. Then it was tears of liberation and hope. And on the last day - tears of sadness. We didn't want to leave.

This is all for you

For the children, the meeting is an incredible event. Here, in a comfortable and safe environment, they can learn a lot of new and important things about the virus, therapy and their wider health. They can calmly talk about HIV without being ashamed. Psychologists, consultants, doctors and invited specialists work at the meeting - they know how to properly impart important information and help children work out their concerns and fears.

Naturally, these events aren’t just work. There are new friends to make, swimming in the lake, quests, team games, yoga, discos and other fun. However, this year the team had very little free time, the programme was jam packed. The organisers had to keep within the five day limit - for financial reasons. Right up until the last moment, everyone was afraid that the meeting might not take place. But thankfully the money was collected just in time.

Some children admitted, as they left the event, that it was "the best week of their lives". It touches us to hear this, but it scares us that this week might not have happened at all.

Treatment is boring, but there’s no way forward without it

HIV treatment is the most important topic at the meeting. An infectious diseases doctor, tells children in a detailed, yet playful way, about HIV - how it acts and how medicines affect this process.

The main task is to convey to the children the importance of treatment, teach them to independently take their treatment, and treat it responsibly.

“You can't help but take your pills, your life depends on them - but it’s hard for a child to fully accept this idea.”

Children who were born with HIV have been taking treatment since childhood. Medicines are part of their lives. Treatment fatigue is a common phenomenon. Pills "don't climb into your throat", syrup that “you want to spit out", adults make you feel guilty when you flushed your pills down the toilet because you don't want to take them anymore. Professional psychologists, consultants and doctors work with these problems at the meeting.

Several children resumed taking medication at the meeting - and these are lives saved by the meeting.

"For our own good, we take these pills," said one of the participants.

In memory of Diana

HIV is not a deadly disease... if treated.

Diana is a girl who has had HIV since birth. She came to the meeting several times, first as a participant, then as an assistant. She was a young activist who helped teenagers living with HIV. Diana was bright, interesting, cheerful and active. She someone you could look up to. But sadly, she is no longer with us.

Diana died, at the age of 18, from opportunistic infections after she stopped taking her treatment. She fell in love, moved in with her boyfriend and stopped taking her pills because she was afraid she would rejected if her boyfriend discovered her status. Fear was so strong that common sense could not overcome it. Diana was killed by STIGMA.

When serious health problems arose, the guy, of course, found out about her HIV status anyway. “What do you think happened? Did he turn away from her?” Svetlana Izambayeva asked the children who listened to Diana’s story, mouthes open.

Everyone was silent. No one could even imagine that the guy was with Diana to the end, feeling sorry that she hadn't told him earlier about her diagnosis. Unfortunately, the doctors couldn't save her.

Diana was dedicated to making the meeting last year happen. So, everyone was concerned about her death. It was hard to believe. Diana knew EVERYTHING about HIV, about treatment and what happens when you stop. But she didn't choose herself and her health, she followed the stigma. She didn't even ask for help - her FEAR and self-stigma was so strong.

The most emotional moment at the meeting

The most vivid and memorable for many participants was the exercise 'People with HIV and People without HIV'. During one of the classes, as they talked about stigma, Svetlana Izambayeva asked those who are not living with HIV to stand up and take to the stage.

This surprised many people, as it turned out that many people living without HIV came to the rally. Nobody had even thought about it. It didn't matter whether a person had HIV or not, exactly until it was asked.

It was unpleasant to “stand on different sides of the barricades". It was a feeling of separation that was unpleasant. It shouldn't be. They were with us, here, just five minutes ago.

“Do you want to do something?” Svetlana Izambayeva asked the audience. What do you think needs to be done to get rid of that unpleasant feeling?

It was a touching moment - when children and adults living with HIV began to approach those without HIV and hug them. No one was ashamed of their tears at that moment.

In fact, there is no reason for division between people with and without HIV. We live in the same society, we should have equal rights and opportunities. You just need to act, not hide. It felt like a revelation to many.

"I realised that everyone, absolutely everyone, is the same," said one of the participants.

A bright future for everyone

Adolescents living with HIV have the same prospects as all other children. And this needs to be communicated to them. The most important idea, that surprised many, is that a person living with HIV can safely build a relationship with an HIV-negative partner. And there are plenty of positive examples of such relationships.

Adults living with HIV came to the meeting to share their experiences, both professionally and in their personal lives. Many of them are in serodifferent couples and have children who are free of HIV. They have interesting jobs, and they live openly with HIV.

"Living examples" give hope. Children leave the event inspired and determined. Some teenagers begin to blog on social networks, many go into activism and social work, some decide to share their status and live openly, some acquire a new self-confidence. These events give children a positive boost, a lot of new friends, plus, they even get cool photos from professional photographers.

It is also important to note that independent support groups continue to work after the meeting, offering continued support in their region.

Thank you, thank you, thank you

We would like to thank Svetlana Izambayeva, her team of professionals, and Ekaterina Stepanova for organising and hosting this event.

Thank you to all the psychologists, doctors, counsellors, consultants, activists, parents, photographers and journalists who have made every effort to ensure that this meeting takes place.

Further thanks go to actor Askar Ilyasov ("Patent Zero"), who came to the event and gave a lot of positive motivation to children and adults, as well as drawing attention to the problems facing teenagers living with HIV.

Special thanks to everyone else and the other organisations who took part in the fundraising.

P.S. In the near future, a series of interviews with teenagers living with HIV will begin in the "Collage" section. We were interested to know how children look at the problem of HIV stigma, what they think, feel and what plans they make for life. Don't miss it!

A woman from Barcelona has been living with an undetectable viral load for more than 15 years after she stopped taking antiretroviral treatment. The woman cannot be considered “cured” as HIV has not completely disappeared from her body, rather she is in “long-term remission” in the absence of antiretroviral drugs - this is often referred to as a “functional cure”.

Of the few people who have truly been cured of HIV have achieved this through stem cell transplantation in order to treat cancer, the donor cells carried the CCR5-delta-32 mutation which prevents HIV penetrating immune cells. There are, however, a small group of people who can keep HIV under control without treatment - these are referred to as “Elite Controllers”.

This new case of functional cure was presented by Dr Nuria Climent from the IDIBAPS clinic. The woman is being referred to as the ‘Barcelona Patient’. At the age of 59, she was diagnosed with acute HIV infection - at which point her viral load was around 70,000 copies and her CD4 at about 800.

The woman joined a small clinical trial of various immunomodulatory drugs (NCT00979706). In total, 20 people took part in the trial. Participants received standard antiretroviral therapy, consisting of lopinavir/ritonavir, tenofovir (TDF) and lamivudine for nine months, as well as a short course of cyclosporin A (an immunodepressant).

During a short planned treatment break, she received a drug that stimulates the production of leukocytes and interferon-alpha (cytokine that regulates the congenital or non-specific immune system). She then resumed ART, alongside a short course of interleukin-2 (cytokine, which activates T-cells and natural killer cells).

Eight weeks later, at which point she had an undetectable viral load, there was another planned treatment interruption - but this time her viral load remained undetectable. As well as undetectable viral load in blood plasma, the researchers noted “pronounced and progressive” reductions in viral reservoirs. This was evidenced by a 98% decrease in total HIV DNA, and 94% decreased in integrated proviral DNA in CD4 cells.

The researchers conducted a genetic analysis and found that the woman did not have any “classical genetic factors” associated with natural control of HIV - including HLA B*57 or the CCR5-delta-32 mutation. Further analysis also showed that her T-cells were susceptible to penetration by HIV. The virus was also not found to be “defective”, something that is common in people who are elite controllers.

When studying the woman’s immune system more closely, the researchers found that her natural killer cells (NK) and CD8 T-cell killers were playing a key role in the fight against HIV. Moreover, she had higher levels of specific natural killer cells (such as NKG2C+) and T-killer cells (gamma delta CD8 T-cells) - something which is usually observed in people with untreated HIV following a normal progression. These cells types are strongly associated with powerful cytotoxic activity against HIV-infected CD4 cells.

Dr Climent did not provide detailed results on the other 19 people involved in the trial, but did tell reporters that this woman was the “only one who was able to control HIV in the long run”.

This pilot regimen is not suitable for widespread use in HIV treatment, but this case study can help researchers develop new strategies for long-term remission that may be of use to all people living with HIV.

At the current time, all people living with HIV should continue to follow their HIV healthcare team’s advice and take their treatment accordingly.

The majority of speakers invited to launch the AIDS 2022 conference highlighted the discriminatory and bureaucratic procedure for issuing visas to conference participants. Many participants, even after engaging in the long visa process, were denied entry to Canada. Even UNAIDS’ Executive Director, Winnie Byanyima, faced increased scrutiny on arrival in Canada.

The host of the ceremony, Canadian actor, model, writer and gay activist Omar Sharifa Jr. called the visa procedure “absurd” and added “Canada, we can be better”.

The highlight of the ceremony for us was the protest, which began immediately after the opening words form the event organisers - the International AIDS Society (IAS). A group of activists with posters took to the stage, chanting “Give us a stage! People are dying! This is our conference! This is a conference for the community!”

"We do not welcome the decision of ViiV Healthcare and the Patent Pool. HIV prevention tools should be available to everyone without exception!" said one activist.

The activists listed their demands as follows:

• Affordable diagnosis and treatment of tuberculosis and cryptococcal infection
• Equitable access to vaccination programs
• Provision of all available types of pre-exposure prophylaxis (PrEP)
• Decriminalisation of HIV
• Equitable access to HIV treatment, care and support
• Increased funding for HIV programmes

Finally, the activists demanded that future AIDS conferences should no longer be held in countries where there is racism, where sex work, drug use and HIV continue to be criminalised.

The heart was transplanted to a 60-year-old patient who suffered from sever heart failure. The operation lasted four hours, and the patient also received a kidney transplant at the same time. Following the operation, the patient spent five weeks in hospital, and is now discharged and regularly seeing the transplant team for monitoring.

"Thanks to significant medical advances, people living with HIV are able to control the disease so well that they can now save the lives of other people living with this condition. This surgery is a milestone in the history of organ donation and offers new hope to people who once had nowhere to turn," said Ulrich P. Jorde, MD, Section Head - Heart Failure, Cardiac Transplantation & Mechanical Circulatory Support, and Vice Chief, Division of Cardiology at Montefiore.

In 2013, the United States passed the HIV Justice Act, which allows people living with HIV to donate their organs to another HIV positive person. But, according to experts, it took almost ten years for this opportunity to become a reality for heart transplantation.

How would the new vaccine work?

Intranasal vaccines contain protein immungens modified by lipids, which form amph proteins. This compound increases the degree of absorption of the vaccine through the nasal mucosa - which ultimately stimulates the mucous membranes and systemic immunity in the fight against viral diseases, including HIV and COVID-19.

"One of the key advantages of this strategy is the high probability that a greater concentration of antigens will reach the mucous membrane," the researchers say.

Testing has shown that amph proteins are preserved in the mucous membrane of the noses of mice and non-human primates, and are actively absorbed by the tissue. This leads to increased immune responses.

According to the researchers, intranasal immunisation with amph-conjugated proteins caused 100 to 1000 times higher titers of antigen-specific IgG and IgA in serum, respiratory mucosa and distal parts of the genitourinary system in animals - when compared to unmodified proteins.

"These results indicate that the use of ampha protein vaccines to deliver antigen through the mucous membrane epithelium is a promising strategy to improve mucous immunity against HIV, SARS-CoV-2 and other infectious diseases," said the authors of the study.

Further testing in this area will continue, says the report.

Currently the City of Hope Patient is the oldest person to receive such treatment. He had been living with HIV for more than thirty years, longer than any previous patient who has entered a state of remission.

“I never thought I’d live to see the day when I wouldn’t have HIV anymore” said the man.

The patient was diagnosed in the late 1980s, when the HIV epidemic was just starting to gain momentum. He, like many others at that time, considered it a “death sentence”. Most of his friends died of HIV before antiretroviral treatment was available.

Bone marrow transplant

At the age of 63, the man developed a blood cancer. Doctors decided that the best treatment would be a bone marrow transplant. By coincidence, the donor had a CCR5 mutation that “does not let HIV into the cells” - essentially conferring a natural immunity to HIV.

Currently, the City of Hope Patient has an undetectable viral load, and the man has been in a state of remission for more than 17 months - he also no longer takes antiretroviral treatment.

The first person to be cured of HIV was Timothy Ray Brown, known as the Berlin Patient. He also underwent a bone marrow transplant to treat leukaemia. As a result of his treatment, Brown was able to be cured of HIV. Unfortunately, at a later date Brown had a recurrence of cancer. This time, the doctors couldn’t help him anymore. Timothy Ray Brown died in September 2020, and in 2021 a monument to him was erected in San Francisco.

Will there ever be a universal treatment?

According the experts, bone marrow transplants “will not revolutionise treatment” for the 38 million people living with HIV. This is a complex, dangerous and expensive procedure with serious side effects. In addition, it is not suitable for all patients. But further cases, such as the City of Hope Patient, give us more and more data in the hope of a CCR5 based treatment in the future.

In addition to participating in the ‘In Danger’ press conference, Life4me+ journalists were given the opportunity to speak to UNAIDS’ Strategic Information Advisor, Lev Zohrabyan, about the ongoing situation in Eastern Europe and Central Asia (EECA) - one of the regions where the number of new HIV cases has continued to increase year on year.

Overview of global data

Process in HIV prevention and treatment is slowing down around the world, and in some regions where we have previously seen a decrease in new HIV diagnoses - increases have begun. Against the backdrop of the global COVID-19 pandemic the amount of resources allocated to the HIV response has decreased significantly.

As a result, 1.5 million new infections have been registered over the past year, which is three times higher than the previously set targets. Additionally, the number of people living with HIV who started treatment was at a 10 year low in 2021.

In 2021, a new infection occurred every two minutes among young women and girls. 

There is a disproportionate number of new infections amongst young women and girls. The reasons are numerous, but are thought to include: 

• Lack of HIV prevention and treatment services
• Gender-based violence
• Gender-based discrimination
• Limited access to resources and education
• Depriving women and girls of control over their sexual life and reproductive health.

In 2021, the number of people living with HIV was 38.4 million, of which 54% were women and girls.

The total number of AIDS related deaths in 2021 was 650,000. One death every minute.

Despite the availability of effective HIV treatment and prevention, the number of deaths remains at a frighteningly high level. Key populations have suffered the worse during the crisis. 

For example, in El Salvador, the HIV prevalence rate among men who have sex with men has almost doubled, and amongst transgender people it has gone up eight times.

Racial inequality also has a big part to play. In the United States and United Kingdom, the number of new cases is higher in people of colour. Moreover, in Australia, Canada and the United States, the HIV infection rate in indigenous communities is higher than non-indigenous people. 

10 million people living with HIV do not have access to antiretroviral therapy. Only 52% of children living with HIV are receiving vital medication. 

Eastern Europe and Central Asia

Despite the alarming data contained within the UNAIDS ‘In Danger’ report, in an interview with UNAIDS’ Strategic Information Advisor Lev Zohrabyan, there were some positive changes that were worth highlighting in the EECA region.

These include, the development of a HIV diagnosis and treatment database that covers various countries in the region. The development process is being accompanied by the introduction of new, modern, methodologies and technologies. A new community monitoring system is also being developed, aiming to improve the quality of preventative measures and services. 

“For example, new digital platforms are being created in Moldova, as well as a number of other countries, that allow you to clearly monitor the situation in compliance with human rights”, said Zohrabyan.

These platforms will allow monitoring of, not only the quantity, but the quality of services being provided - in real time. In other words, the region is actively working to promote non-discriminatory services for people living with, or at risk of HIV, along with monitoring the legislative framework.

“It should be noted that communities in Ukraine have shown their viability and commitment to providing services to those in need, despite difficult conditions, devastation and failure in established systems” added Zohrabyan.

The situation, when it comes to prevention of vertical transmission (sometimes called mother-to-child transmission), is also looking good. The lack of published data is because numbers remain so low. 

Why, along with the feminisation of the HIV epidemic, are prevention and treatment programmes still often aimed mainly at men?

The most important factor the affects the spread of HIV to women and girls is unequal access to services and uneven distribution of resources. 

It is necessary that the scientific community, national governments and the civil sector recognise that fact and quickly pivot to provide prevention and care programmes in the right direction.

Evidence suggests that the number of new HIV cases among women is higher than among men. This should be the basis for changing stereotypes that have stubbornly remained since the beginning of the HIV epidemic - when most cases were detected amongst men who have sex with men, and injecting drug users. According to UNAIDS experts, the key to solving this situation is prompt and appropriate responses to up-to-date data.

In terms of net figures, how many times will it be necessary to increase funding for HIV programmes in the region to achieve the 2030 goals?

“This is a very difficult question that I cannot answer. The trajectory of the epidemic is currently going in the wrong direction” Lev Zohrabyan admitted.

At the same time, Zohrabyan explained that some countries are very close to achieving the 2030 goals, whilst int he EECA region the trend of the epidemic has continued to consistently rise. 

Given the geopolitical situation, it is almost impossible how much more funding is necessary to bolster healthcare and grants for non-governmental organisations critical to solving the epidemic.

“Instead of consolidating efforts against challenges such as coronavirus, monkeypox and other natural threats, people are separated and huge amounts of money is spent on taking lives and sowing grief (war). In these conditions no healthcare system can cope with the HIV epidemic. That requires peace, stability, and stable financing” Zohrabyan added in conclusion. 

You can read the UNAIDS ‘In Danger’ report here: https://indanger.unaids.org

How is HIV related to joint pain?

People living with HIV can experience pain for the following reasons:

• In the first few weeks the virus can causes symptoms similar to the flu, or a bad cold, which cause joint pain and discomfort.
• Various conditions such as injuries, infections, bone disease and ageing can increase the risk of arthritis or rheumatic diseases.
• Medicines that are used to treat HIV, and other diseases, can also cause joint pain.
• The HIV virus itself can cause inflammation which can lead to joint and muscle pain.
• ARV therapy and joint problems

Some antiretroviral treatments for HIV can cause unwanted side effects, including joint pain. Most often these will present within one to two months after starting treatment. But joint pain can also be triggered by drugs for other conditions, cholesterol-reducing drugs and hepatitis treatments, for example.

Which joints are most likely to experience pain in people living with HIV?

Pain related to HIV infection can occur in any joint. But, according to research, the larger joins of the arms and legs are the most likely to cause issue. Moreover, pain seems to usually manifest asymmetrically.

Treatment methods

There are various methods of treating joint pain. It depends entirely on the cause of the disease or pain itself. Non-steroidal anti-inflammatory drugs, steroids and opioids are often used. Non-chemical methods of treatment can include physical therapy, massage, physical activity, acupuncture, electrical stimulation and more.

It is important that people do not self-medicate when it comes to pain, and that you raise any issues with a healthcare professional who can build a complete picture of your issue and help you choose a safe and effective therapy path.

Marburg is a highly infectious disease, similar to Ebola, which does not currently have a vaccine or approved treatment. The Ghanian authorities are currently working to mitigate the spread of the virus, and the WHO is collecting resources and sending specialists to the country. The article was published in The Washington Post. 

“Health authorities have responded swiftly, getting a head start preparing for a possible outbreak. This is good because without immediate and decisive action, Marburg can easily get out of hand,” said the WHO’s regional director for Africa, Matshidiso Moeti.

What is the Marburg virus?

Marburg is a rare, but very contagious, hemorrhagic fever virus. According to the WHO, mortality rates range from 24% to 88% depending on the strain of the virus and the quality of the treatment received.

Experts suggest that Marburg virus passes to humans from the fruit bat, Rousettus, as a result of prolonged contact in mines and caves.

The virus can actively spread between people who come in direct contact with biological fluids (blood, saliva, urine, semen) as well as via surfaces and materials. The bodies of people who die of Marburg may remain contagious during and after burial.

According to the CDC, the virus is “not native” to continents outside Africa. In Europe, the first outbreak of the disease was recorded in 1967. It is thought that the virus was transported to Europe from Uganda. Seven deaths were recorded during that outbreak.

Symptoms of Marburg

Over a number of outbreaks experts have been able to observe the way the Marburg virus affects people. The disease is said to begin “suddenly” - with high fevers, sever headaches and malaise. Muscle pain and convulsions are also common symptoms. Both patients from Ghana had nausea and vomiting.

By day five, a rash may appear on the chest, back and abdomen. In the most severe cases, death occurs around day nine after the onset of the disease.

Is it possible to treat Marburg?

There are currently no vaccines or antiviral agents approved for the treatment of the Marburg virus. But, according disease experts, supportive therapy can improve the condition of the patients and improve their chance of survival.

Rehydration with oral or intravenous fluids, maintaining oxygen levels and treating specific symptoms as they occur are the main methods used to support patients with Marburg.

Some experts also believe that drugs designed to treat Ebola may help in the treatment of the Marburg virus - but more research is needed.

Radiological and CT diagnostics are expensive and ineffective for the early and accurate detection of subclinical tuberculosis, so researchers from Germany and the United States studied the use of blood-based biomarkers in combination with sputum analysis. The study, called AFRICOS, lasted for five years, and the results were published in Medicalxpress magazine. 

"The progression of latent TB to active disease can be life-threatening to people living with HIV, so an early biomarker for active TB disease could be a critical tool to profoundly improve clinical outcomes for patients with this co-infection." said Col. Julie Ake, M.D., the director of MHRP and the AFRICOS lead investigator.

AFRICOS study

The study was conducted from 2013 to 2018 in several African countries. 2,014 people living with HIV took part in the testing.

During the period of observation participants were screened for the active form of TB using the Xpert MTB/RIF diagnostic test. In addition, the team studied longitudinal samples of mononuclear blood cells before, during and after the diagnosis of tuberculosis in patients with an active and latent form of the disease.

Based on the samples collected, the researchers analysed the activation station of MBT-specific CD4 cells as a surrogate biomarker for diagnosis tuberculosis in patients who are HIV positive.

Results

Laboratory analysis showed that the MTB-specific activation of CD4+ T-cells distinguished active TB from latent TB with a sensitivity of 86%. In many cases, the transition of latent to active TB (as shown by the analysis of the MTB-specific T-tells) began 6-12 months before the diagnosis of clinical symptoms, and the appearance of bacterial in sputum.

The data obtained from AFRICOS indicates that the use of a blood-based biomarker can contribute to the early detection of tuberculosis. This, in turn, will improve the clinical outcomes of the disease, as well as help stop further the spread of tuberculosis.

Previous clinical trials have shown that the use of a single bNAb can lead to viral rebound in blood samples. This is due to the fact that some strains of HIV can survive the treatment process. In this situation, a combination of bNAbs may be a more effective approach.

In order to find the best combinations, Dr Colin LaMont and his colleagues from the Max Planck Institute for Dynamics and Self-Organisation in Germany used a computational approach. The team used high-performance sequencing to analyse the generics of viral samples collected over 10 years from eleven people living with HIV who had not previous received therapy. The team then used this data to predict which viral strains might avoid treatment by various bNAbs. They then applied their computation approach to find the optimal combination of antibodies that is least likely to allow the virus to “slip away”.

According to the results of their study, the scientists came to the conclusion that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01. This combination therapy targets three different areas of the HIV capsid, the virus’ protective outer shell, and reduces the likelihood of viral rebound to less than 1%.

Researchers suggest that the combination of bNAbs administered intravenously every few months, combined with modern antiretroviral therapy, can “improve the long-term success of HIV treatment” and suggest that more research is needed in this area.

The summer camp team includes HIV experts, activists and psychologists from Ukraine, Kyrgyzstan and Germany. The camp’s programme consists of both interactive and theory learning sessions, movie screenings, theatre and much much more.

If you are aged between 16 and 20 years old, and:

• Live with HIV
• Need help and support
• Want to help other teens unite and create communities
• Live in any EU country
• Want to spend August in a new and exciting way

Then fill out our Google form here.

The last day for submitting an application is: Saturday 30th July 2022

The costs associated with attending the camp will be covered by the event organisers.

If you’re brining a parent, they will also need to fill out a questionnaire.

Places are limited, so be sure to apply as soon as you can.

For any questions, please email: contact@life4me.plus

In honour of the 30th anniversary of the fight against HIV, in just one night, more than 170 talented actors, dancers and circus performers were able to fundraise a total of $1,890,000 for Broadway Cares/Equity Fights AIDS (BCEFA) reports Poz.com. 

This year’s show was a return to in-person performance, with the previous two years being held online due to COVID-19.

Covering the past 30 years of Broadway Bares, the show revisited hit numbers from the past three decades - with 90s dance beats, superheroes, greek mythology and Disney classics.

Two of the largest donations, at $200,000 each, were from the MAC AIDS Foundation and Broadway Bares superfan Dwight Curry.

To see some of the highlights this year, check out this YouTube video:

https://www.youtube.com/embed/HDMC-9P3hfY?rel=0&hd=0

We know that HIV prefers a special kind of immune cell, CD-4 T-cells. There are, however, several variants of the cell and it has been difficult for experts to determine exactly which one is “more attractive” to the virus - and why.

Aiming to solve this puzzle, a team from the Gladstone Institute combined the CyTOF-Lec method (used to study the protein profile of individual immune cells) with a special PP-SLIDE tool for cell profile reconstruction. Their results highlighted two important discoveries:

First, HIV prefers to infect CD4 memory T-cells with the largest amount of two types of sugars on their surface: fucose and sialic acid. Further experiments have confirmed that sialic acid is necessary for HIV to effectively infect CD4 T-cells.

Second, HIV forces the infected cell to produce more of these sugars.

According to the researchers, it is these abilities of HIV that allow infected cells to survive, since sialic acid is associated with evasion of immune surveillance. Hiding from the immune system, infected cells are more able to quickly gain a foothold and spread throughout the body.

With the use of sugar-based biomarkers these cells are now more able to become a therapeutic target. In the future, scientists plan to test the CyTOF-Lec method on samples of infected cells exposed to antiretroviral therapy.

A protein called Pol affects the process by which HIV reproduces and is distributed throughout the body. Pol HIV is broken down into 3 enzymes (protease, reverse transcriptase and integrase) that work together to construct a mature form of the virus. Protease plays a crucial role in this process.

To understand this mechanism, the team used cryogenic electron microscopy, one of the imaging methods that revealed the structure of the Pol HIV protein molecule. As a result, experts found out that Pol is formed by two proteins bound together. This discovery came as a surprise because other similar viral proteins are single-protein assemblies. And in this bilateral structure, the protease component Pol is "weakly connected" to the reverse transcriptase component. It is this feature that is a prerequisite for the maturation of the virus.

The team believe that they have managed to identify a new vulnerability in HIV that could be affected by drugs. Experts plan to continue research in this area and "pay close attention to the role of integrase in assembling a mature form of the virus during replication."

In a previous study, American scientists found out how HIV chooses immune cells for infection. It turns out that the virus prefers CD4 T-cells with the largest amount of of two types of sugars on their surface: fucose and sialic acid.

Chronic infection of Hepatitis C virus (HCV) can lead to severe liver diseases, including cirrhosis and cancer, as well as neuropsychological disorders. For example, people with cirrhosis may develop liver encephalopathy, in which toxins in the blood lead to impaired brain function. However, a stable virological response to antiviral treatment (characterised by an undetectable viral load 12 weeks after the completion of DAA therapy) leads to improved neuropsychological health and improved quality of life for the patient.

Research

Scientists from the Institute of Medical Education in India conducted a study to investigate this connection.

385 people with HCV aged 18 to 65 took part in the tests. Of these, 75% were men, and 21% were diagnosed with liver cirrhosis. Most people contracted HCV through non-sterile injections, surgery or injecting drugs.

Participants passed a series of tests at the very beginning of the study and 12 weeks after the completion of DAA therapy. At enrolment, patients showed a significant decrease in cognitive functions compared to a healthy general population.

Results

Around 91% of patients achieved a stable virological response; 88% of people with cirrhosis and 91% without cirrhosis were cured. Those who successfully passed therapy had less depression and anxiety. They also had improved concentration, reaction time, information processing skills, as well as visual, short-term and working memory. But in patients who were not cured, the test results remained at the same level or, in some cases, worsened.

When the researchers compared cognitive functions in humans with HCV and non-alcoholic fatty liver disease (NAFLD), the first group showed gave the worst results.

Experts note that there is a heightened risk of HCV reinfection amongst people living with HIV, especially in men who have sex with men who have recently recovered from HCV. Regular screening is recommended in this group.

Down’s syndrome is when someone is born with an extra chromosome. They usually get an extra chromosome by chance, because of a change in the sperm or egg before birth. People who have Down’s syndrome will have some level of learning disability. This means they’ll have a range of abilities. Some people will be more independent and do things like get a job. Other people might need more regular care.

Many people with Down’s syndrome undergo cognitive stimulation therapy, but there are currently no biomedical treatments for patients. Currently, experts are working with retrotransposons - these are DNA segments that change their location in the genome, creating RNA copies of themselves. Retrotransposons can be introduced into certain areas of the genome and located in areas that stimulate genes associated with the condition.

Retrotransposons quickly replicate inside cells, which makes them look like the human immunodeficiency virus (HIV). According to experts, HIV and retrotransposons need the same molecule to copy themselves: the inverse transcriptase enzyme. The drug lamivudine belongs to the category of drugs that block reverse transcriptase, this means it has the potential to help people with Down’s syndrome.

During the animal testing process, experts were able to confirm this theory. Mice who received lamivudine for four months had improved cognitive functions, including memory and motor activity. Researchers suggest that these advantages of lamivudine may be related to its effect on one or more variants of the APP gene.

Additional clinical trials will be conducted to confirm whether the effect is present in humans. Scientists also plan to test its effectiveness against Alzheimer's disease.

Previous studies have shown that ritonavir, another HIV drug, can help people with neurological disorders.

Peripheral artery disease can lead to problems with the heart, blood vessels and blood circulation. At the same time, a low CD4 cell count and diabetes can both dramatically increase the incidence of the disease and lead to serious complications. 

Disease of the peripheral arteries is characterised by the formation of atherosclerotic (fatty) plaques in the abdominal aorta, pelvic artery and lower extremities, which impacts blood transfer leading to problems with the delivery of oxygen and nutrients to tissues. Early symptoms are cramps in the calves during training and a feeling of heaviness in the legs.

The study was conducted with the participation of 844 people:

• The average age was 50.
• 86% were men.
• 95% had an undetectable viral load.
• One in four smoked (the rest were former smokers).
• 40% had high blood pressure.
• 45% had high cholesterol.
• 34% were overweight and 10% obese.
• 7% had CD4 cells below 350 and 15% of participants were in a state close to AIDS.
• They had been living with HIV for an average of 13 years, and taken ART for an average of 10 years.

The study showed that within two years, 30 particiapnts had developed a peripheral artery disease that then passed without symptoms, An analysis adjusted for age, gender, smoking showed that the diagnosis was associated with diabetes and a low CD4 cell count. Scientists also identified a trend of the disease with each decade of antiretroviral treatment.

Summing up, the researchers noted that the basic prevalence of peripheral artery diseases was two times higher in people living with HIV than in the general population. Scientists believe that further HIV-negative research is needed to clarify HIV-related risk factors.

ODYSSEY involved 707 children and adolescents from Germany, Portugal, South Africa, Spain, Thailand, Uganda, Great Britain and Zimbabwe. Over 22 months, 350 of the participants received DTG therapy, and the remaining 357 received standard treatment (a combination of 3-4 ARV drugs). Both groups included participants who had not previously been treated for HIV, as well as those who had ineffective previous treatment.

The results of the study showed that 47 patients from the DTG group (13%) and 75 patients from the standard therapy group (21%) faced clinical treatment failure. In addition, adolescents who received DTG had significantly fewer cases of serious drug resistance mutations.

“These results show that dolutegravir is superior in terms of preventing children from developing treatment failure,” said lead author Anna Turkova, MD, a research clinician at the MRC Clinical Trials Unit at UCL and consultant paediatrician at Great Ormond Street Hospital, in London.

According to experts, this study provided sufficient evidence to update the WHO manual, as well as to increase access to DTG for children living with HIV. However, it is necessary to conduct additional research on the use of DTG in paediatrics to study an potential psychiatric side effects.

The new B-cell treatment makes use of the CRISPR system (think of it like cut, copy and paste on your computer), to detect, cut and edit type-B leukocytes, which are responsible for the production of antibodies against viruses. In this case, the experts used two adeno-associated viral vectors, one of which encodes Staphylococcus aureus Cas9 (saCas9) and the other -3BNC117, antibody against HIV.

Following the introduction of these vectors to mice, researchers recorded successful editing of B-cells, which leads to memory preservation and secretion of bNAb antibodies at neutralising titers of up to 6.8 μg/ml.

"All animals who were treated had a large amount of desired antibodies in their blood. We isolated these antibodies and made sure that they really effectively neutralised HIV in the laboratory," says Dr Adi Barzel, one of the authors of the study.

The authors of the study expect that in the coming years they will be able to use this method to product treatments for HIV and other infectious diseases - including some cancers.

What does "human-oriented language" mean?

These are situations when in the wording a person is put first, not the disease or its other features. For example, not "drug users", but "people who use inject drugs", not "HIV-positive", but "people living with HIV". This may include the refusal to use abbreviations (LWH, LUIN, etc.) - but opinions vary on this.

Such deliberate choice of wording is also being used in other health and rights based movements.

"This means that we are more than our state of health or our actions - we are primarily human”

Research

Dr Kristen McPherson and her colleagues conducted a cross-study study of the use of person-oriented language in HIV-related publications. They analysed 237 studies, published in English, between 2017 and 2021.

During the analysis, the team found that the expressions "HIV-infected" and "AIDS-infected" were used in 57% of the articles, and "HIV patients" or "AIDS patients" - in 30%.

Dr. McPherson notes that the phrase "AIDS-infected" is considered illiterate from either a clinical or biological point of view - and the continued use of such expressions in scientific publications is "shocking”.

"Language evolves: we used to be ‘victims’ of the virus or ‘suffering’ with the virus, and now we’re people living with it. It’s important to recognise the way language can be triggering, especially for those who’ve lived during the earlier days of the epidemic.” McPherson believes.

What to do?

Dr. McPherson and her colleagues have presented a number of recommendations to tackle this problem.

1. Researchers should consult UNAIDS and other organisations on wording issues and replace terms that are considered stigmatising.
2. Journal editors can play a significant role in combating HIV-related stigmatisation, by raising stigmatising language when it is used, and both replacing it and educating the original author.
3. Remember that sometimes it is clinically relevant and necessary to use terms sometimes considered stigmatising. That said researchers and clinicians should do their best to use the most appropriate language at the correct time.

One-hundred-and-twenty people who were living with HIV and virally suppressed were surveyed, using the EQ-5D-5L questionnaire, which assesses quality of life in across with five areas: mobility, self-care, daily activities, pain/discomfort and anxiety/depression.

For the most part, those surveyed reported a high level of quality of life (80%). Higher rates were also noted for mobility, self-care and daily activities (work duties, household chores, leisure activities).The pain/discomfort and anxiety/depression sections scored lower, however.

More than 30% of the respondents said that they do not feel supported by society. Social factors, such as stigmatisation, reduce well-being indications by as much as two times.

"Self-reported outcomes by PLHIV in our survey show that they can enjoy a similar quality of life to those without the disease. This is remarkable and an encouraging call for the clinical community to support their clients to achieve success in viral suppression." said Dr Chien-Yu Cheng, co-author of the study and Chief of the Division of Infectious Diseases, Taoyuan General Hospital.

The easiest, safest and most effective way to protect yourself from diseases is vaccination. There are vaccines that are recommended routinely for adults and children, tetanus and measles for example. Others are indicated on an individual basis, depending on certain circumstances (vaccination against rabies, typhoid fever and yellow fever etc).

What is a ‘natural protective mechanism’?
Our body has many ways to protect against pathogens which contain an antigen - an element that is recognised by the immune system as alien, this leads to the production of antibodies.

When the human body first meets an antigen, it takes time for the immune system to react and produce antibodies against it. At this point, when antibodies have not yet been produced, there’s a high probability that the person may get sick.

Along with the production of antibodies, the body creates memory cells, which also being to produce antibodies. Thanks to these memory cells, should the same pathogen re-infect the body, the immune system will immediately start producing antibodies and protect the person from that disease.

How do vaccines work?
Vaccines teach the immune system to create antibodies to a specific virus before the body is every exposed to it in the real world. Vaccines are often made from “killed” or “weakened” forms of the pathogen which cannot lead to the disease in question.

Vaccination not lonely protects the people who are vaccinated, but also those who cannot be vaccinated, such as young children or people who severe allergies to components of the vaccine - such people can be protected if they live amongst a well vaccinated community.

Why can’t vaccination be postponed?
There are increased risks of serious illness from diseases such as measles, meningitis, tetanus, polio and rubella.

If an outbreak of any disease beings, there may not be enough time to get the full protected effect of the vaccine. This is especially true for vaccines which are given over a course of several doses, such as hepatitis B.

Are vaccines safe?
First, all vaccines that reach the market undergo large-scale clinical trials.

Secondly, even after the end of testing experts continue to monitor information and efficacy of the vaccine.

Thirdly, there is an independent body for vaccine quality control - the Global Advisory Committee on Vaccine Safety.

Contraindications
For most vaccines, the only absolute contraindication is anaphylaxis - a severe allergic reaction to the vaccine or one of its components. People with immunodeficiency, for the most part, should not be administered “live” vaccines. Any other issues are usually temporary and can be carried out later.

Remember!
The risk of serious health consequences as a result of the disease is many times higher than any small risk associated with vaccination.

Smallpox (pox) is a highly contagious disease caused by the Variola virus. The disease is characterised by a severe disease course, high fever, a rash on the skin and mucous membranes. Those infected can end up with scars and partial or complete loss of vision. Mortality ranges from 20% to 40% (with some epidemics reaching 90%). People who’ve had smallpox have a strong natural immunity to the disease going forward.

How did the world manage to eradicate such a highly infectious and deadly disease? Vaccination. In 1796, The British doctor Edward Jenner discovered that by infecting people with a much more mild virus called cowpox they were conferred immunity against the much deadlier smallpox virus. In 1958 the World Health Organisation (WHO) began a global vaccination programme using a modern vaccine. By 1980, the WHO declared smallpox completely eradicated and recommended ended planned vaccination for the virus. Only two samples exist of the smallpox virus, one in the Russian State Scientific Centre “Vector” and the other in the American Centres for Disease Control and Prevention.

Monkeypox is a rare infectious disease caused by Orthopoxvirus (part of the family Poxviridae). It is not as infectious as smallpox, and mainly distributed in remote areas of Central and West Africa. Symptoms of monkeypox are nausea, fever, rash, itching, muscle pain and skin lesions. Most cases present in a mild form of the disease, but severe cases are possible. The mortality rate ranges from 1% to 10%. The virus is transmitted by airborne droplets or close physical contact with the infected person or their belongings.

Cases outside the region are usually related to travel. An outbreak of monkeypox is currently occurring in the UK, Europe and North America - with the most cases being detected in the UK.

Will the smallpox vaccine help against monkeypox? In the USSR, vaccination against smallpox was mandatory until 1980, in the UK and USA their programmes ended in 1971 and 1972 respectively. Experts say that the immunity from these vaccinations will protect against other pox viruses, including monkeypox.

Monkeypox is part of the Orthopoxvirus family. Other viruses in this branch include, human smallpox, cowpox, racoonpox and more. These viruses are all very similar to each other, so the vaccines used previously protects against these various pox viruses - via cross-immunity.

Specialists are not yet calling for global vaccination at this time, rather asking people at higher risk to come forward and get vaccinated. The vaccine can also be used as post-exposure prophylaxis for those who have been in contact with an infected individual. For everyone else the advice is to avoid contact with infected individuals, observe good hygiene standards, and consult your healthcare professional at the slightest suspicion of infection.

A group of researchers assessed the safety and tolerability of a full dose of chemotherapy in the treatment of a cancer that is common in people living with HIV. The study into the paclitaxel and carboplatin (PCb) based treatment was published in Oncology Nurse Advisor.

The researchers selected 16 patients for 64 cycles of chemotherapy. The participants were divided into two groups:

• Group One: Receiving antiretroviral treatment - including the CYP3AR inhibitor, ritonavir.
• Group Two: Receiving antiretroviral treatment - without ritonavir.

Participants received carboplatin and paclitaxel intravenously every three weeks for a maximum of six cycles. Participants were assessed every two cycles using radiological studies and tumour response.

Each participant managed at least two cycles, with the median number being four cycles.

Three participants had a partial response, ranging from 16 to 22 months, six participants stabilised, and two patients experienced toxicity of grade three or higher. The most common consequences of the toxicity were granulocytopenia (40%), infection (15%) and anaemia (15%).

Concluding the study and based on the results, the authors wrote that people living with HIV may be given a full dose of PCb to treat their cancer and that there is no need to reduce the dose of anti-tumour therapy - regardless of antiretroviral therapy.

Data from a study undertaken by the Department of Public Health in Washington State from 2013 to 2021 was used for the analysis. Of the 1,098 MSM adults who were diagnosed with HIV during this period 797 (73%) were interviewed about their experience with PrEP.

Approximately 1 in 4 (25%) of participants who were diagnosed with HIV in 2020/21 reported that they had previously taken PrEP or had used it inconsistently. More than 50% of previous PrEP users were diagnosed within six months of stopping PrEP.

The researchers identified several main reasons for the refusal or discontinuation of PrEP:

• Confidence that the individual has a low risk of HIV infection (13%)
• Side effects (13%)
• Problems with the cost of PrEP and insurance that covers it (13%)
• Homelessness, unstable housing, moving to a new area (10%)

Less common reasons included pill burden, discussing their doctors visits, and difficulties getting an appointment.

The analysis shows that all areas of the health system need to work together to improve PrEP uptake and adherence.

Firstly, it’s important to make sure that information about PrEP is correct and up to date. Patients should be advised about potential side effects and how to mitigate them, and an open dialogue should be maintained between patient and healthcare professionals. Secondly, the burden of follow-up for PrEP patients should be reduced where possible.

"Clinics may need additional innovations to expand opportunities, such as higher availability of telemedicine, online STI testing, home testing for STIs, as well as home PrEP monitoring and care for asymptomatic people," says Dr. Chase Cannon of the University of Washington.

A previous study showed that around 41% of people who start taking PrEP discontinue is within the first six months. Heterosexual men and women were the mostly likely to discontinue PrEP (72%) whilst men who have sex with men and trans women were least likely to stop PrEP (31%).