When they’re hospitalized due to COVID-19, people who are living with HIV generally appear to fare similarly to HIV-negative people, though they experience a range of immunologic and inflammatory abnormalities, according to new research presented on July 9 during the 23rd International AIDS Conference (AIDS 2020).
The studies are among the largest to date exploring COVID-19 severity among people with HIV, but they ultimately offer little clarity on the interplay between the two viruses. That puts them in line with most of the other research that has been published to date regarding the relationship between HIV status and COVID-19 prognosis.
Both AIDS 2020 presentations were of retrospective studies conducted in New York City, where COVID-19 struck particularly hard from early March through May. One study involved 100 adults living with HIV and 4,513 HIV-negative adults hospitalized for COVID-19 within the Montefiore Health System in the Bronx; the other involved 93 people living with HIV who were admitted to one of five unnamed New York City emergency departments with acute COVID-19.
Montefiore Study: HIV Doesn’t Alter COVID-19 Outcomes, but Viral Suppression Might
The Montefiore study was presented by Viraj Patel, M.D., M.P.H., an assistant professor of medicine at the Albert Einstein College of Medicine in New York City. The data he presented focused on admissions that took place between March 10 and May 11 in the Bronx, a New York City borough of 1.4 million people that is home to a particularly high percentage of people with HIV (roughly 2% in 2018, according to Patel) and is predominantly Black and Latinx. At the height of the COVID-19 outbreak in early April, the Montefiore system was admitting more than 1,000 people per day for complications related to the novel coronavirus.
Utilizing access to electronic health records alongside chart reviews, Patel et al found that HIV status had no impact on odds of death while hospitalized with COVID-19 or the duration of hospitalization: 22% of the 100 hospitalized people with HIV died, compared to 24% of the 4,513 HIV-negative people. The average length of hospital stay was five days for both groups. The researchers also noted no significant difference in occurrence of acute kidney injury between the groups.
On the other hand, Patel et al spotted what appeared to be a higher rate of intubations (21% versus 14%) and a longer period of time spent intubated (by 54%) among the HIV-positive group.
When stratifying their findings by HIV viral load, the researchers found that all of the intubations—and, in fact, all of the in-hospital deaths—that occurred among people with HIV took place in those whose viral load was suppressed (i.e., below 40 copies/mL). On the flip side, people with an unsuppressed viral load appeared to spend 58% longer in the hospital prior to discharge compared to virally suppressed patients. Patel offered no explanation for these findings during his presentation, instead urging further research into this area.
David Alain Wohl, M.D., a professor of medicine at the University of North Carolina School of Medicine, who was not involved in the research by Patel et al, found the viral load discrepancies intriguing, but not particularly concerning. “It’s a tantalizing finding that plays into the narrative that maybe people without viral suppression are more immunodeficient, and that that’s somehow protective,” Wohl said, referring to prior research suggesting that a weakened immune system may be less likely to mount an overaggressive response to COVID-19 that can result in a life-threatening cytokine storm.
However, “Precision is pretty challenging here,” Wohl warned. “There were only 100 people in the ‘living with HIV’ group, and only 15 were not virally suppressed. Just a few people with different outcomes, by chance, can make a huge difference.”
In addition, Patel noted in his presentation that although his research team adjusted for some potential confounders—including age, body mass index, gender, lung disease history, and race—they did not adjust for all, nor did they take into account any COVID-19 treatments that may have been given.
“The potential for unmeasured confounding: That’s big,” said David Malebranche, M.D., M.P.H., an associate professor of medicine at the Morehouse School of Medicine. (Malebranche was also not involved in this research.) He noted the wide array of comorbidities that are particularly common among people living with HIV and that are also associated with COVID-19 severity, such as cardiovascular disease history, diabetes, and high blood pressure.
“The message, to me, would be: Viral suppression is not the end of everything,” Malebranche said. “You still have to take other precautions [as a person living with HIV], still have to watch your blood pressure, still have to check your weight. If you’re on an integrase inhibitor–based regimen, you still have to check your HbA1c. You still have to check all these other chronic illnesses.”
Mount Sinai Study: Suppressed CD4, Heightened Inflammation
Another HIV-specific COVID-19 study presented at AIDS 2020 focused specifically on markers of immune response and inflammation. John Hsi-en Ho, M.D., an assistant professor of medicine at New York City’s Mount Sinai Hospital, shared a selection of outcomes from a retrospective chart review of 93 people living with HIV who tested positive for SARS-CoV-2 after presenting at one of five emergency departments in New York City between March 2 and April 15.
This was early in the course of New York’s surge, and major outcomes reflect those challenges: 72 of the 93 individuals were hospitalized, and 19 (26%) ultimately died; the rest have since recovered.
Among a subset of 30 patients for whom pre-COVID CD4 data were available, significantly depressed CD4 counts were seen relative to pre-COVID-19 levels (down from an average of 464 cells/mm³ to 188 cells/mm³). CD4 percentages were similarly down among a subset of 26 patients (from 28% to 23%).
Ho et al noted that, although the CD4 count at which patients presented with COVID-19 did not significantly differ between those who died and those who recovered, nadir absolute lymphocyte counts were dramatically reduced among those who died. Several markers of inflammation—peak C-reactive protein, peak interleukin-6, and peak interleukin-8 (though not D-dimer, fibrinogen, or TNF-alpha)—all were also significantly higher among patients who died compared to those who did not.
Much as with Patel’s presentation, Ho did not attempt to draw any conclusive findings from his team’s research. There was no HIV-negative comparator group in this study, and Ho stated that the study was naturally biased toward only highlighting results from the sickest patients. (Ho also noted that no stratification of outcomes by viral load was possible, since a detectable viral load was recorded in only 11 of the 68 patients for whom pre-COVID-19 viral load data were available.)
Instead, Ho et al’s research appeared to be aimed at codifying the effects of acute COVID-19 on lymphopenia and inflammation among people living with HIV, and affirming that immune dysregulation is part of the risk profile that can put people with HIV at risk for a particularly severe COVID-19 disease course.
For Malebranche, any clinical relevance of the findings is limited at best. “In HIV, even when you’re [virally] suppressed, the immune system is dysregulated,” he noted.
The Takeaway: New Data Points, but No Broader Conclusions
In fact, it may not be possible to glean clinically relevant takeaway messages from either of the main studies presented at AIDS 2020 regarding HIV and COVID-19. “What part of this is specifically SARS-CoV-2 related—to some kind of immune dysregulation or immune hyperinflammatory state?” Malebranche asked. “What part of it is related to HIV? What part of it is just that, when you’re sick, this is what happens—it has nothing to do with either of the viruses? From these studies, it’s hard to tease that out.”
The AIDS 2020 research, even as it adds a cache of new data, ultimately slides in alongside other small case studies that to date have proven inconclusive regarding links between HIV and COVID-19. And Malebranche doesn’t see that scenario dramatically improving anytime soon—not until we begin to get a significant amount of prospective study data in studies that utilize control groups and can properly adjust for confounders. “It’s kind of all getting jumbled in the mix, and I don’t think we have a clear picture just yet,” he said. “It’s going to take a few more months, if not a year or two—or more—to tease out exactly what is going on here.”
That’s a challenge for any health care provider who is facing anxious questions from their patients living with HIV, but it’s part of the reality of the present, Malebranche said. “People are getting very frustrated, because they want the answers now. And it’s not gonna happen.”