EACS & BHIVA release updated guidance for HIV & COVID-19

The European AIDS Clinical Society (EACS) and the British HIV Association (BHIVA) have released an updated statement on the risks of COVID-19 for people living with HIV (PLHIV). 

Data on ongoing worldwide studies of new coronavirus therapy and infection risks for PLHIV were last published by organizations in early April 2020.

COVID-19 and HIV

Both organisations assessed the results of an analysis into a series of cases in patients with both COVID-19 and HIV. So far there is no evidence for a higher COVID-19 infection rate or different disease course in PLHIV than in HIV-negative people.

Available evidence suggests that the risk of a more serious COVID-19 disease course increases with age, male gender, and some chronic diseases, including CVD, lung disease, and diabetes.

Most people in Western Europe diagnosed with HIV are undergoing antiretroviral therapy meaning that they should have a good CD4 count and an undetectable viral load. This means they should be at no more risk of either contracting SARS-CoV-2 or having a worse disease than someone their age, gender and general health – who doesn’t have HIV.

That said, nearly half of people living with HIV in Europe are aged over 50. With age comes a greater likelihood of chronic diseases. Both of which are associated with higher risk during this pandemic.

Smoking is also a risk factor for respiratory infections, so all patients should be encouraged to stop or limit their tobacco consumption. 

Flu shots and pneumococcus vaccines should be done in a timely manner. 

Immunosuppression, as evidenced by a low CD4 T cell count (<200 / μl) and/or lack of antiretroviral treatment, is also associated with an increased risk of more severe COVID-19.

For patients with a low CD4 count (<200 / ml) and those experiencing a decrease in CD4 during COVID-19 infection, it is recommended that prophylaxis of opportunistic infections (OI) be started.

The first reports from China indicate a growing amount of evidence of vertical transmission of COVID-19. However, to date, the clinical outcome in newborns has been very good.

Experts from both organisations believe that everyone should carefully follow the national guidelines approved by states to reduce the risk of infection and reduce the spread of COVID-19.

COVID-19 Treatment: Antiretrovirals & further options

Expedited research and publication are welcomed with the caveat that results may be disseminated pre-publication and/or published without usual peer review process.

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

The first randomized clinical trial of lopinavir / ritonavir (also known as Kaletra) did not demonstrate any clinical benefit compared to standard treatment in 199 adult patients with severe COVID-19.

Despite the lack of in-vitro data to confirm the antiviral activity of TDF / FTC (also known as Truvada) against SARS-CoV-2 and very limited binding data, Spain is planning to conduct a randomized, placebo-controlled phase 3 study using a combination of TDF / FTC and low doses of hydroxychloroquine (HCQ ) as a prevention of COVID-19 in healthcare workers. However, the fact that PLHIV who were on TDC / FTC treatment have become infected with SARS-CoV-2 it’s unclear how much protection it will provide.

Currently, there is no evidence 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 pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. PrEP should be taken as directed and there is no current evidence that PrEP is effective against COVID-19.

A recent series of hydroxychloroquine cases with or without azithromycin has not been shown to demonstrate clear clinical benefits despite in-vitro inhibition of SARS-CoV-2. Only one small clinical study showed a tendency to shorten the time until recovery of patients and short-term improvement 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 FDA has granted emergency use of hydroxychloroquine and chloroquine for some hospitalized patients with COVID-19.

Of great concern are recently published results from a retrospective analysis of data from patients hospitalised with confirmed SARS-CoV-2 infection in the United States which found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with COVID-19 and even found an association of increased overall mortality in patients treated with hydroxychloroquine alone. As a consequence, the FDA now cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm 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 drug use in patients with COVID-19 showed potential clinical benefits.

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

Preliminary data on remdesivir were also recently presented in a NIAID (National Institute of Allergy and Infectious Diseases) press release following the COVID-19 Adaptive Therapy Test (ACTT), which included 1063 patients with progressive COVID-19 and lung damage.

According to experts, those who took remdesivir recovered faster than patients who received placebo. In particular, the average recovery time was 11 days for patients receiving remdesivir, compared with 15 days for those receiving 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 the results of its 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. At the initial stage of the SIMPLE study, which was not a placebo-controlled, 397 patients with severe COVID-19 were randomized. The latter received intravenous injections of remdesivir for up to five or ten days in addition to standard treatment. 

Recently, an extension of the study phase has been announced, which will recruit an additional 5,600 patients, including people on mechanical ventilation. 

COVID-19: data collection and resources

A special web portal covid19-druginteractions.org has been created to help track studies into experimental COVID-19 treatments, as well as check drug-drug-interactions. EACS and BHIVA provide are pleased to offer financial support to this venture.

The authors also highlighted two more resources for the monitoring and reporting of COVID-19 cases:

• The NEAT ID Foundation has developed a ‘data dashboard’ to monitor COVID-19 case numbers, hospitalisations and mortality in people with HIV at European and country level. The data will be available for public viewing via www.NEAT-ID.org.
• The Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) launched by the German Society for Infectious Diseases (DGI) and ESCMID’s Emerging Infections Task Force (EITaF) an open register based on anonymous questionnaires and they are keen to collaborate with other registries. See https://leoss.net, contact them by email at [email protected] and the register can be accessed here https://leoss.net/statistics