BHIVA & EACS release updated statement on COVID-19 & HIV

On Monday, May 25, the British HIV Association (BHIVA), in collaboration with the European AIDS Clinical Society (EACS), DAIG, GESIDA and the Polish AIDS Science Society, released an updated statement on the risks of COVID-19 coronavirus infection for people living with HIV (PLHIV).

Data on ongoing worldwide studies into possible COVID-19 therapy and the risks of infection to PLHIV were last published at the end of last month.

COVID-19 and HIV

Since the start of the pandemic, data on a series of cases of COVID-19 in HIV patients have been published in China, Spain, Germany, Italy and the USA. However, to date, there is still no clear evidence that suggests that PLHIV have a higher risk of becoming infected by SARS-CoV-2 or a different course of the disease.

It should be noted that in most cases, PLHIV who present with COVID-19 tend to be of a younger age than those without HIV, but the rates of comorbidities were comparable across both groups. A British cohort study presented data from 16,749 hospitalised with COVID-19. Of these, only 1% were PLHIV, however HIV did not appear to adversely affect survival rates.

Available data indicates that the risk of serious complications increases with age, male gender, and some chronic diseases, including cardiovascular disease, lung disease, obesity and diabetes.

Although most people living with HIV and taking antiretroviral therapy have a normal CD4 T-cell count, an undetectable viral load and may not be at an increased risk of serious complications, some PLHIV still have reasons to be cautious.

Nearly half of people living with HIV in Europe are over 50. With age comes an increased likelihood of living with one or more chronic diseases such as those previously mentioned.

Smoking is also a high-risk factor for respiratory infections, all patients should be advised to stop or limit their tobacco consumption. Flu shots and pneumococcus vaccines should be done in a timely manner. 

Immunosuppression, indicated by a low CD4 T-cell count (<200/μl) or not receiving antiretroviral treatment, are also associated with an increased risk of more severe COVID-19 disease.

For patients with a low CD4 count (<200/ml) and those experiencing a decrease in CD4 during COVID-19 infection, it is recommended that clinicians initiate opportunistic infection (OI) prophylaxis to prevent further complications from possible OIs.

The ongoing discussions around potential vertical transmission of COVID-19 remain controversial. Although a few reports have claimed perinatal transmission of COVID-19, vertical transmission of COVID-19 have not been detected in a number of other large observation series. Pregnant women with critical COVID-19 who deliver during their disease course mostly deliver preterm via caesarean section. So far clinical outcome of the newborns however, has been uneventful.

COVID-19 Treatment: Antiretrovirals

The authors of the statement emphasised that any research and publications, including those conducted in an emergency format, should be welcomed on the condition that their results be disseminated before publication and/or published without the usual peer-review process. 

Discussions and studies on the antiviral activity of certain anti-HIV drugs that may have some effect on COVID-19 remain ongoing.

The first randomised clinical trial of lopinavir/ritonavir did not show any clinical benefits compared with standard care in 199 adult patients with severe COVID-19.

An Italian case series suggested that darunavir also does not prevent SARS-CoV-2 infection in people living with HIV and does not protect against disease complications.

In silico data suggests that TDF/FTC may bind to SARS CoV-2 Nsp1 protein, while two other studies show that TDF and TAF may be SARS-CoV-2 polymerase inhibitors, but there is still no in-vitro data to support the antiviral activity of TDF/FTC against SARS-CoV-2. A large, randomised, placebo-controlled phase 3 study in Spain is currently planned, using a combination of PrEP TDF/FTC and low doses of hydroxychloroquine (HCQ) as a prophylaxis for COVID-19 in healthcare workers.

Currently, “no evidence is available to justify switching a patient from their usual antiretroviral therapy. Additionally, there is no evidence to support HIV-negative people taking antiretrovirals outside the context of PrEP to prevent HIV acquisition – PrEP should be taken as directed and there is no current evidence that PrEP is effective against COVID-19” the EACS and BHIVA emphasised.

COVID-19 Treatment: Other Approaches

A recent cases series on hydroxychloroquine, with or without azithromycin, has not been shown to demonstrate clear clinical benefits despite in-vitro inhibition of SARS-CoV-2, probably due to methodological problems.

Only one small randomised clinical trial (RCT) showed a tendency to shorten the recovery time of patients when taking hydroxychloroquine. However, other data showed no benefits in terms of virus clearance, clinical or radiological endpoints.

Thus, to date, not a single acute viral infection has been successfully cured by any of these drugs. Despite this, the US Food & Drug Administration (FDA) has granted emergency use of hydroxychloroquine and chloroquine for some hospitalised patients with COVID-19. 

Of serious concern are the recently published results of a retrospective analysis of data from patients hospitalised with confirmed SARS-CoV-2 infection in the United States who showed no evidence that the use of hydroxychloroquine, with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalised with COVID-19, and even found a link to increased overall mortality in patients treated with hydroxychloroquine.

Later, two other observational studies were published on treatment with hydroxychloroquine, azithromycin, or two drugs at once, or neither – the studies showed no difference in in-hospital mortality and/or intubation rates.

Finally, a multinational registry analysis for the treatment of COVID-19 in more than 96,000 people was published online, which could not confirm the benefits of hydroxychloroquine or chloroquine when it was used alone or with macrolide in a hospital. Each of these treatment regimens was associated with reduced survival and increased ventricular arrhythmias in the treatment of COVID-19. 

As a result, the FDA now warns against using hydroxychloroquine or chloroquine as an anti-COVID-19 drug outside hospitals or clinical trials because of the risk of heart problems.

Another potential candidate against COVID-19 is remdesivir, originally developed to treat Ebola. Remdesivir has broad in-vitro antiviral activity against SARS-CoV-2. The first cases of treatment with remdesivir in patients with COVID-19 showed potential clinical benefits.

More recently however, the results of the first randomised clinical trial in China have been announced. They showed that remdesivir was not associated with statistically significant clinical benefits when treating adults with severe COVID-19. Moreover, in 12% of cases, remdesivir was stopped early due to treatment-related side effects. The study was stopped at the initial stages due to the low registration of patients.

Preliminary data on remdesivir was recently presented in a NIAID press release following the Adaptive COVID-19 Treatment Trial (ACTT), which included 1063 patients with advanced COVID-19 and lung damage. According to experts, those who were randomised onto remdesivir recovered faster than patients who received a placebo. In particular, the average recovery time was 11 days for patients receiving remdesivir, compared with 15 days for those receiving a placebo. The results also indicate survival benefits: the mortality rate was 8.0% in the remdesivir group and 11.6% in the placebo group (p = 0.059). 

Meanwhile, Gilead also announced results from their late-stage SIMPLE study, showing that a five-day duration of taking remdesivir led to a “similar improvement in clinical status” as the 10-day treatment presented in the NIAID study. The initial stage of the SIMPLE study, which was not a placebo-controlled, randomised 397 patients with severe COVID-19 to received either a 5-day or 10-day course of remdesivir alongside standard care. 

Recently, an extension of the study phase has been announced, which will include an additional 5,600 patients, including those receiving mechanical ventilation.

Famotidine was the third agent recently associated with improved clinical presentation and outcome of COVID-19. Examining 6,212 records of patients with COVID-19 in China, doctors noticed that many of the surviving patients suffered from chronic heartburn and were taking famotidine rather than the more expensive omeprazole. Hospitalised patients with COVID-19 treated with famotidine died with a frequency of about 14% compared with 27% of those who did not take the drug, although the result was not considered statistically significant. Currently, about 200 critically ill patients with COVID-19, including many on mechanical ventilation, were enrolled in a New York study of 1,174 people.

Maintaining HIV care during the COVID-19 pandemic

The introduction of quarantine and social distance measures has meant reduced access to standard HIV testing which has increased the challenge of achieving UNAIDS’ first goal 90-90-90 globally.

Moreover, during the COVID-19 pandemic timely linkage to care and continued access to ART have proven difficult since healthcare professionals from HIV clinics are now increasingly involved in caring for patients with COVID-19, this has been increasingly apparent in Central and Eastern Europe. In countries with high COVID-19 case loads clinics should be preparing to work under minimal medical resources and make retaining patients on ART their primary goal. Non-governmental organisations should assist where possible with the goal of ART continuity.

COVID-19 data collection and resources

A COVID-19 drug interactions website www.covid19-druginteractions.org has been developed for the experimental drugs being trialled to treat COVID-19 in different parts of the world. EACS and BHIVA are happy to announce that they have agreed to financially support this very useful website. In addition to it, two more resources have very useful data on cases of COVID-19:

• The NEAT ID Foundation, which developed a “data dashboard” to monitor the number of COVID-19 cases, hospitalisations and deaths among people living with HIV: www.NEAT-ID.org
• The German Society for Infectious Diseases (DGI) and the ESCMID Task Force for Infectious Diseases (EITaF) have launched the Lean European Open Survey on SARS-CoV-2 (LEOSS) – an anonymous questionnaire monitoring for the spread of the SARS-CoV-2 virus.
• EASL is supporting a registry which can be found under the following link https://www.covid-hep.net/

You can also find out more about HIV drugs and their use against coronavirus on the specially developed thematic portals “ Coronavirus & HIV Q & A ” for people living with HIV and “ Specialized clinical information on coronavirus COVID-19” for specialists.