COVID-19 and HIV: What Happens When Two Infectious Diseases Meet?

One of the major worries during the early days of the COVID-19 pandemic is whether the disease would be especially severe and deadly among people who were immunocompromised, particularly among people with HIV. Suppressed immunity would seem to make people more vulnerable to infection with the SARS-CoV-2 virus that causes COVID-19. There was, however, a significant “on the other hand.” As it became a clear that severe cases of COVID-19 were the result of a dysregulated, hyperinflammatory response, it was possible that a suppressed immune system would be, if not protective, at least be a mitigating factor in having a severe case of COVID-19.

Now, two years into the pandemic, researchers have some insights into people with HIV have been affected by COVID-19. The darkest fears of what might happen have not come to pass. And there is even a silver-lining story that the antiretroviral therapy — Truvada (emtricitabine and tenofovir disoproxil fumarate) in particular — that many people with HIV take to control their disease may protect against severe cases of COVID-19.

A group of Spanish researchers led by Julia del Amo, a researcher in the division of HIV, STI, viral hepatitis and TB control in the Spanish ministry of health, published a concise but nuanced review of research and resulting evidence about people with HIV and their vulnerability to COVID-19 in the journal AIDS earlier this month. They organized the review around several important questions. Of course, the studies they reviewed were conducted before omicron because the dominant variant.

Are people with HIV more likely to be tested for COVID-19 than people without HIV?

During the first wave the pandemic, a study among U.S. suggested that the answer is yes. Greater testing might have created a false impression that people with HIV were more likely to get infected.

Are people with HIV at higher risk of SARS-CoV-2 infection than people without HIV?

Del Amo go through the studies, and some suggest the answer is yes, they are. But it is highly qualified “yes: because people with HIV may be at higher risk for COVID-19 because of socioeconomic factors; once statistical adjustments for those confounding factors are made, the difference disappears. The conclusion that Del Amo and her colleagues draw is that evidence so far is that the people with HIV do not have a greater risk of SARS-CoV-2 infection other than through factors associated with socioeconomic vulnerability and risky behavior.

Are people with HIV at higher risk of serious cases of COVID-19 than people without HIV?

This is, of course, a different and perhaps more important question than whether people with HIV are more vulnerable to infection, which may lead to a mild or even asymptomatic case. Del Amo and her colleagues cite a half-dozen studies that suggest that people with HIV are more likely to experience severe COVID-19, and evidence of higher risk remains in some of those studies even after statistical adjustments for comorbidities. Yet Del Amo and her co-authors come to a hesitant conclusion that the available evidence is “compatible” with people with HIV being more likely to experience severe COVID-19. But they also hit the brakes, cautioning that arriving at a firm conclusion is impossible because of study designs and the difficulties of coming up appropriate comparison groups. They also cite a study that they say is the only one that compared people with HIV with people from the same population that made extensive adjustment for confounding factors. That study did not find a greater risk of severe COVID-19 among people with HIV.

Which factors are associated with severe COVID-19 among people with HIV?

Regardless of whether people with HIV are at the same, higher or lower risk of experiencing a severe case of COVID-19, the factors associated with severe COVID-19 might be different in people with HIV than those without HIV. They review the results of five studies in this section of the review. Their takeaway is that there is nothing special about the factors influencing COVID-19 case severity for people with HIV and that it varies with age and comorbidities in pattern without HIV. Two cases series found an association between low CD4+ counts and a higher risk of COVID-19 , but the reviewers say the evidence for CD4+ counts and HIV viral loads isn’t clear.

What is the role of antiretrovirals in influencing COVID-19 infection and severity?

The role that antiretrovirals might play in protecting people against COVID-19 is an intriguing subplot that has emerged from the research into COVID-19 among people with HIV. Del Amo was the lead author of a study published in the Annals of Internal Medicine in October 2020 that looked at the incidence and severity of COVID among people with HIV taking antiretroviral. The study included 77,590 people with HIV receiving antiretroviral therapy, 236 of whom were diagnosed with COVID-19 and 151 hospitalized. There were 20 deaths from COVID-19. When they analyzed patients by the type of antiretroviral, they found that those taking Truvada were 57% less likely to be diagnosed with COVID-19 than those taking tenofovir alafenamide and emtricitabine, a combination sold under the brand name Descovy, and 48% less likely to be hospitalized. Similarly, they found a lower risk of diagnosis (37%) and hospitalization (20%) among patients at three hospitals that treated patients predominately with Truvada compared with the patients at the 27 hospitals that predominately treated patients with Descovy. In the review, del Amo and her coauthors mention a study in South Africa that also suggested that Truvada fended off SARS-Cov-2.

The Annals study and the review discuss the “biological plausibility” for antiretrovirals providing protection against HIV and for tenofovir, in particular, having properties that might interfere with the virus and also temper the immune response if an infection does occur.