HIV in the Time of COVID-19

As 2020 draws to a close, we asked David Alain Wohl, M.D., a professor of medicine in the Division of Infectious Diseases at the University of North Carolina and a highly respected HIV clinician-researcher, to take stock of the year's most momentous research developments and other critical events. In this exclusive series of articles, Wohl calls attention to 10 such developments that have tremendous short-term implications for our day-to-day efforts to improve HIV prevention, treatment, patient care, and policy in the U.S., and analyzes each development with his trademark wit and clinical savvy.

When I called to check in on him, my patient of more than 20 years told me, “I don’t go near anybody but my dog, and haven’t since March.” His commitment to maximum SARS-CoV-2 avoidance was shared by most of the patients living with HIV I spoke with during our COVID-19-proof telemedicine visits. “I have enough going on; all I need is COVID,” another said.

Their caution is understandable, and staying away from other Homo sapiens is a prudent approach we should all emulate. Underlying their self-imposed lockdowns, though, was a concern that their HIV infection placed them at a heightened risk for SARS-CoV-2 infection and severe COVID-19. However, it still remains unclear whether SARS-CoV-2 poses any greater threat to people living with HIV infection than it is to those who are HIV-negative—although the bulk of data we have thus far obtained is more encouraging than not.

Assumptions that the HIV infected—especially those with a lower-than-normal CD4 cell count—would be more susceptible to this new respiratory virus have, so far, not been backed by much evidence. In fact, reports from Spain from early in the outbreak suggested people living with HIV were less likely be infected. In the U.S., established cohorts of people with and without HIV infection—including the Veterans Aging Cohort (VACS) and a combination of the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS)—failed to find a clear signal that HIV is a risk factor for COVID-19.

However, these were early looks, taken as the virus was first germinating within the U.S. At the time of the VACS analysis, there were only 253 cases of COVID-19 out of the thousands of study participants. The MACS/WIHS relied on telephone surveys with 3,411 participants, conducted mostly in May. Although more of those who reported they were diagnosed with COVID-19 were HIV positive (11% versus 6%), only 13% of those surveyed said they had ever been tested for SARS-CoV-2 infection.

Meanwhile, hospital data have been mined to discern whether HIV infection increases the risk for worse COVID-19 outcomes once infection does occur.

An analysis by a team from the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) in the United Kingdom examined records of 54,000 people hospitalized with COVID-19 across 207 medical centers from January through June.
Of these patients, 122 (0.26%) were known to be HIV infected, almost all on HIV therapy. Importantly, the hospitalized patients with COVID-19 who had HIV infection were younger (median age 56 versus 74), presented with more symptoms, and had fewer recorded comorbidities than the COVID-19 inpatients who were HIV negative.

The proportions of people with and without HIV infection who died by 28 days after admission were not significantly different: about 30% overall. However, after adjusting for the age disparity, HIV positivity was associated with a 47% greater risk of death.

This difference in mortality was most evident in those who were less than 60 years of age. Below this age, HIV-positive status more than doubled the risk of mortality after adjusting for sex, ethnicity, age, baseline date, comorbidities, and COVID-19 disease severity at presentation (as indicated by a record of hypoxia or receipt of oxygen therapy). The latter adjustment was done given an important consideration: Medical providers may have had a lower threshold for admitting to the hospital people who were living with HIV and experiencing COVID-19 symptoms.

A pre-print report from New York State also compared COVID-19 testing and hospitalization outcomes by HIV status. From March to June, almost 3,000 people living with HIV in the state were diagnosed with COVID-19. When the 108,000 people the state has in its registry of people living with HIV was used as the denominator, that amounted to an incidence rate of 27.7 per 1,000. By comparison, among the more than 19 million New Yorkers not known to be HIV positive, 375,000 were diagnosed with COVID-19 during this period—for a rate of 19.4 per 1,000.

However, after adjusting for age, sex, and region, this difference in the rates of COVID-19 by HIV status lost statistical significance. Similarly, once hospitalized, people living with HIV had mortality rates that were not distinguishable from those not diagnosed with HIV infection after adjustment for confounders.

That being said, the report found that HIV-positive people were 40% more likely to be admitted for COVID-19 than the rest of the population, with hospitalizations occurring more often for those with a low CD4 cell count or higher viral load. But again—as with the ISARIC study—this may simply mean that 1) people living with HIV infection had more reason to be admitted due to underlying conditions or 2) health care providers were more motivated to admit those who appeared to be coinfected with HIV and COVID-19.

While the clinical consequences of COVID-19 for people living with HIV have remained somewhat uncertain, other studies have demonstrated more definitive impacts of COVID-19 on the well-being of people living with HIV, as well as those at risk for acquiring HIV.

Several studies point to COVID-19 leading to interruptions in or barriers to HIV treatment, especially as lockdowns were ordered and clinics transitioned to virtual visits.

Access to HIV pre-exposure prophylaxis (PrEP) has also been disrupted. At Boston’s Fenway Health Center, a major PrEP provider, new prescriptions for PrEP dropped 72% over the first four months of 2020. Over the same period, there was a 20% decline in clients with an active PrEP prescription, and sexually transmitted infection (STI) testing became almost non-existent.

Clean syringe programs were also largely suspended, and there is considerable concern that sharing of injection equipment will fuel outbreaks of hepatitis C and HIV that would be slow to be recognized given the limited amount of screening taking place due to COVID-19.

The Bottom Line on HIV and COVID-19

The evidence that SARS-CoV-2 hits some harder than others can be found in any intensive care unit in the U.S. Older and larger people—usually with comorbid conditions like diabetes—fill these beds. Whether HIV infection also increases the risk of infection or disease severity remains unclear, but the data are largely reassuring.

That HIV-positive people may be more likely to be diagnosed with COVID-19 is not surprising, as they are often better plugged into health care; this may explain some of the higher rates of infection detected in cohort studies.

In addition, HIV-positive people are more likely to be poorer than those without HIV, and they are more often people of color—a group of communities that are themselves disproportionately impacted by the COVID-19 pandemic. As such, many people living with HIV are essential workers, or due to other reasons they have little choice but to work, take public transportation, and be among others.

On top of all this, people living with HIV infection who do acquire SARS-CoV-2 often have risks that stack the odds toward more severe COVID-19, including chronic heart and lung diseases, as well as obesity.

However, there is one critical area in which COVID-19 does impact people with HIV differently. The burden of isolation, solitude, and fear of contagion that we all carry is heavier and harder to shoulder for many people who are living with HIV. A seemingly endless season of rising case counts and climbing mortality is darker for those already struggling with emotional challenges, keeping addictions kicked, financial pressures, and pervasive stigmatization.

Regardless of any interaction between HIV and SARS-CoV-2 on a pathophysiological level, the pandemic’s disruption of HIV care is irrefutable. Clinics across the country have been, are, or will be shut to face-to-face visits, and HIV care providers are often being pulled to care for those with COVID-19. Telemedicine has become a tenuous tether for maintaining care at a distance, and some patients are falling through the gaps.

In addition, innovative HIV research has mostly been stopped in its tracks as lockdowns were instituted, research sites were closed, and staff and participants were left with no choice but to retreat to the safety of their homes. Important studies have been delayed for months, if not longer. Ongoing investigations limped along with virtual study visits and incomplete data collection.

Only now are some clinical research efforts cranking back up. The impact of the pandemic on HIV care and prevention—not just now, but also tomorrow—is profound.

The exciting news of a succession of COVID-19 vaccines proving to be highly effective provides hope (and thanks to activist lobbying, people living with HIV infection were included in some of these trials). Vaccines and other preventative interventions, along with encouraging results from trials of treatments for early COVID-19, flicker like an end-of-tunnel light leading to an After Time when we can dance, and hug, and go to movie theaters, and visit Paris.

Until then, despite the reassuring data about HIV and COVID-19, most of my patients are staying put at home with their hoarded toilet paper, pet food, and antiretrovirals.

The Bottom Line on HIV and COVID-19

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