In the early days of the COVID-19 health crisis, there was concern that the novel coronavirus would hit people living with HIV especially hard—either through greater susceptibility to SARS CoV-2 infection or greater severity of COVID-19 illness. Now, over a year into the pandemic, the worst fears about HIV and COVID-19 don’t appear to have materialized; however, many concerns persist, particularly in cases where HIV treatment efficacy is suboptimal or comorbidities are present.
On balance, the research data we have available to date suggests that:
- PLWH have a higher overall risk for experiencing a severe course of COVID-19 than HIV-negative people.
- However, most of this higher risk appears to be tied to issues that are already known to endanger the health of PLWH.
- These issues include, on the HIV treatment side, a lack of effective antiretroviral therapy and the presence of a low CD4 count—particularly a low nadir CD4 count.
- On the health care management side, these issues primarily focus on comorbidities known to exacerbate COVID-19 risk, many of which are more common among PLWH than the general population.
Determining the precise relationship between HIV and more serious COVID-19 outcomes has been a challenge, experts say, because most studies on the subject have been too small, haven’t fully factored in comorbidities, or haven’t entirely taken into account the relationships between antiretroviral use, HIV viral load, and CD4 count.
“Bottom line, if there were a striking relationship between HIV and COVID, we would see it in all the studies,” said Paul Volberding, M.D., a professor emeritus at the University of California-San Francisco (UCSF) and the former co-director of the UCSF-Gladstone Center for AIDS Research. “However, I wouldn’t be surprised if there is some effect. We need a big enough study on all parameters,” including breakdowns for comorbidities, he added.
That said, there are some helpful data among the science that has been published over the past year, even if the results sometimes appear conflicting. They also collectively drive home the continued importance of getting PLWH diagnosed with HIV, into care, and on antiretroviral treatment promptly; on the continuation of that care over time; on the prevention and management of comorbidities; and on the prioritization of PLWH for coronavirus vaccination.
U.S. Study Findings on HIV and COVID Severity
One recent cohort study, published in JAMA Network Open in January, compared COVID-19 outcomes between people known to be living with HIV and people who were not. The researchers gathered data on nearly 3,000 people in New York state based on a combination of HIV surveillance and COVID-19 diagnosis/hospitalization databases, focusing on the time period between March 1 and June 15, 2020.
They found that PLWH across the state were 43% more likely to receive a COVID-19 diagnosis than HIV-negative people and were 2.61 times as likely to be hospitalized. PLWH who had a COVID-19 diagnosis were also 2.55 times as likely to die in the hospital than their HIV-negative counterparts.
As with other similar studies, however, there are significant limitations to these findings. For instance, the study didn’t adjust for comorbidities; a number of significant comorbidities are known to be more common both among PLWH and among those who experience severe cases of COVID-19, including cardiovascular disease, chronic kidney disease, diabetes, and several types of cancer. The study also didn’t separate PLWH who were on effective therapy for HIV from PLWH who were not.
In contrast to the JAMA Network Open study, an older study out of New York City published in Clinical Infectious Diseases found the opposite result: that there was very little, if any, risk of worse outcomes from COVID-19 for PLWH.
The NYC study used data from five hospitals in the Mount Sinai Health System. Crucially, the researchers noted that all 88 of the study patients admitted for COVID-19 were on some form of antiretroviral treatment, with most receiving integrase inhibitor-based regimens. In addition, the majority (58%) of patients who had CD4 measurements taken on hospital admission had a count above 200 cells/mm3.
HIV and COVID-19 Research Findings Outside the U.S.
Globally, data about the relationship between HIV infection and outcomes for COVID-19 infection vary widely—although, again, much of the discrepancy between study findings may stem from how studies did or did not stratify their results by HIV treatment status, immune health, or the presence of comorbidities.
One very large study in England concluded that PLWH had a higher risk for death from COVID-19 than people without HIV—and that the risk was even greater for Black people with HIV, according to findings published in The Lancet HIV in December 2020. The retrospective cohort study analyzed routinely collected electronic primary care data linked to national death registrations for 17 million adults.
Comparing patients who had a primary care record for HIV infection with those who did not, the research team estimated the association between HIV infection and COVID-19 death, and found that people with HIV had higher risk for COVID-19 death than those without HIV—although when adjusting for ethnicity, smoking, and obesity, the risk was somewhat diminished.
The study also did not account for antiretroviral treatment or CD4 count. That’s because researchers used data from primary care facilities, not specialized clinics, where HIV is often managed in the United Kingdom, according to lead study author Krishnan Bhaskaran, Ph.D., a professor of statistical epidemiology at the London School of Hygiene & Tropical Medicine. Bhaskaran told TheBodyPro that other studies have shown around 94% of people with HIV in the UK are on antiretroviral treatment and have well controlled disease with undetectable viral load. Therefore, “we do not think the raised risks we observed can be entirely explained by the minority who are not on treatment and/or have poorly controlled HIV disease,” she said.
Regarding the higher death rates observed for Black people in the study, Bhaskaran speculated that rates of antiretroviral treatment and HIV control might be different in England based on race—as well as rates of coronavirus exposure and COVID-19 illness. “It is also possible that people of Black ethnicity have higher risks of exposure to the new coronavirus, for example due to being more likely to work in occupations with a lot of public contact, and that HIV is exacerbating the higher risks associated with this,” she said.
On a similar note, a separate European retrospective study published in December 2020 in HIV Medicine evaluated risk factors for COVID-19 morbidity and mortality using data from 175 people coinfected with HIV and SARS‐CoV‐2 in three countries—Germany, Spain, and Italy—through June 12, 2020. The researchers concluded that “immune deficiency is a possible risk factor for severe COVID‐19, even in the setting of virological suppression.”
The team specified that “patients with severe COVID‐19 had a lower current CD4 T‐cell count and a lower CD4 T‐cell nadir, compared with patients with mild‐to‐moderate COVID‐19.” They noted, however, that the only factor associated with mortality in their study was a low CD4 T‐cell nadir.
“Although there was no evidence of any direct therapeutic effect of tenofovir (mainly used as TAF) and HIV PIs, data strongly argue against any interruption or delayed initiation of ART in the current pandemic, in order to prevent even moderate cellular immune deficiency,” they wrote. Most importantly, researchers did not compare mortality rates in the cohort with mortality rates in HIV‐uninfected populations.
“Carefully designed seroprevalence studies are needed that have to adjust for important risk factors such as age and comorbidities,” the study authors wrote. “It also remains to be seen whether PLWH with SARS‐CoV‐2 infection differ from PLHW in general.”
A study that made waves earlier in the pandemic, published in Clinical Infectious Diseases in August 2020, included 22,000 patients with COVID-19 in Western Cape, South Africa, among a total study population of 3.5 million, 16% of whom were living with HIV. That study concluded that people with HIV had increased COVID-19 mortality—and, in a somewhat eyebrow raising addendum, that HIV viral suppression made no difference in the risk of death.
However, one of the lead researchers in the study, Mary-Ann Davies, MBChB, MMed, Ph.D., an associate professor at the University of Cape Town, admitted during a discussion about the study that “almost all the people with HIV who died had other comorbidities apart from HIV.” Of those, about half were diabetic and roughly half were hypertensive, both of which are acknowledged risk factors for serious illness from COVID-19—and both of which are more prevalent among PLWH than the general population.
Inconsistency Persists Around COVID-19 Vaccination Priority
Part of the challenge in drawing consistent conclusions across studies on HIV and COVID-19 infection lies in the fact that not all studies equally consider important factors that may influence COVID-19 severity among PLWH, such as whether a person is on treatment for HIV (and for how long, and what type of medications they’re taking, and how effective their treatment is, and how well connected to care they are) or what their current/nadir CD4 count is.
It makes sense that a person with unmanaged HIV—or anyone whose immune system is severely compromised—could lead to worse outcomes from COVID-19, or from many other kinds of infections. This is in part why the Centers for Disease Control and Prevention (CDC) lists HIV as one of the conditions that might increase risk of severe illness from COVID-19.
But what about the many PLWH who are clinically and virologically stable, and who have no serious comorbidities that would independently increase their COVID-19 severity risk? Can PLWH with a normal CD4 count still be considered immunocompromised, and therefore at greater risk of serious illness from COVID-19? The lingering complexities may be why U.S. public health authorities have been slow and inconsistent in their determinations as to where PLWH should be on the prioritization list for COVID-19 vaccination; as of Feb. 16, only 11 states (and Washington, D.C.) had explicitly included HIV infection in their Phase 1c eligibility criteria.
While public health official response has been inconsistent, leading HIV advocacy groups have grown more confident in the body of research supporting vaccination. An alliance of European organizations representing HIV care providers and researchers published a joint statement in January laying out the case for vaccine prioritization among PLWH, and dozens of U.S. organizations signed on to a public comment submitted by AIDS Action Baltimore to the CDC’s Advisory Committee on Immunization Practices on Feb. 28.
Looking to the Future
Dave Wessner, Ph.D., an infectious disease expert and professor at Davidson College in North Carolina, agrees that the body of research so far doesn’t provide clear answers for managing the intersection of HIV and COVID-19. But the research we’ve seen to date still has its value, he contends.
“The immune system is complicated, and HIV is not going away,” Wessner said. “Having a good sense of how new infectious diseases, like COVID-19 or others, play out is helpful going forward.”
In the meantime, for people with untreated HIV and the health workers who are in a position to provide them with care or access to services, Wessner has one bit of advice: “If you have untreated HIV, the most important thing is to get on treatment.” And, of course, encourage PLWH to do what the rest of the population needs to continue doing right now: wear masks, remain socially distanced, and get on lists to be vaccinated to prevent COVID-19 as soon as possible.
Myles Helfand contributed reporting to this article.
[Editor's note: The initial published version of this article understated the extent of the relationship between HIV infection and COVID-19 disease severity. A number of sections within this article were revised on March 3 to more accurately describe and provide context for the study findings available to date.]