In March, the Centers for Disease Control and Prevention (CDC) included HIV (on its list of underlying medical conditions to be prioritized for COVID-19 vaccinations—a triumph for advocates who’d pushed to include people living with HIV (PLWH). The CDC’s exact wording: “Having HIV (Human Immunodeficiency Virus) can make you more likely to get severely ill from COVID-19.”
This messaging could be puzzling or concerning for PLWH who are on effective therapy and undetectable. After all, doesn’t treatment that effectively controls HIV make PLWH not immunocompromised? Yes. Should all people with HIV be lumped in with groups such as those with autoimmune diseases like celiac and lupus, or those who have undergone an organ transplant? Some nuanced guidance would be helpful.
In fact, the CDC made a clearer statement about HIV and being immunocompromised in February, that, “Based on limited data, we believe people with HIV who are on effective HIV treatment have the same risk for COVID-19 as people who do not have HIV.” It further clarified, saying, “The risk for people with HIV getting very sick is greatest in: people with a low CD4 cell count and people not on effective HIV treatment (antiretroviral therapy or ART).”
The marker of a severely impaired immune system is a CD4 count of less than 200, and the CDC estimates that 7% of people with HIV have a CD4 count below that threshold. And a recent article by Anthony Fauci, M.D., and others introduces another consideration about the risk for severe disease outcomes in COVID-19 among PLWH, concluding that “The severity of COVID-19 disease in persons with HIV is related strongly to the presence of comorbidities that increase the risk of severe disease in COVID-19 patients in the absence of HIV.” In other words, it may be comorbidities, or additional co-occuring conditions, and not necessarily HIV—unless, again, it’s uncontrolled HIV—that make exposure to COVID-19 riskier for PLWH. These comorbidities include certain cancers, chronic kidney disease, chronic obstructive pulmonary disease, cardiovascular disease, obesity, and type 2 diabetes.
But what is the exact risk from COVID-19 for, say, someone with HIV and comorbidities who is on ART, versus someone without comorbidities with a low CD4 count? As with many questions about COVID-19 risks and vaccination effectiveness for people who may be immunocompromised, the answer is: More data are needed. And data will be coming. One large observational study, sponsored by the University of Missouri, Columbia, is now collecting data on how PLWH fare when infected with SARS CoV-2, the virus that causes COVID-19. Data will be available next year, but, from what we know so far, it won’t be looking at how well COVID-19 vaccines work on PLWH.
What Do We Know About Vaccine Safety and Effectiveness for Immunocompromised People?
Regardless of your CD4 count and viral load, National Institutes of Health (NIH) clinical guidelines do come down firmly on the side of getting a COVID-19 vaccine, “because the potential benefits outweigh potential risks.” They also note, “Typically, people with HIV who are on antiretroviral therapy (ART) and who have achieved virologic suppression respond well to licensed vaccines.”
As for vaccine safety, the CDC notes that limited data are available, and, “People living with HIV were included in clinical trials, though safety data specific to this group are not yet available at this time.” The British HIV Association (BHIVA) takes a less cautious approach, even suggesting that people with uncontrolled HIV might not be at risk from the COVID-19 vaccines, saying because they are not live vaccines, they are “no less safe in people with damaged immune systems.”
As for vaccine effectiveness for PLWH, you may not be surprised to learn that these issues require more study. PLWH were included late in COVID-19 vaccine trials, and specific data on these participants have not been released in most studies. In theory, COVID-19 vaccines might be weaker in people with a low CD4 count or a high viral load, and/or comorbidities. But so far, the data on COVID-19 vaccine effectiveness for PLWH are mostly encouraging—though the studies are small and, again, make no distinction between PLWH with well-controlled HIV and those with low CD4 counts or detectable viral loads.
A sub-study of a phase 2/3 study of the Oxford/AstraZeneca vaccine recruited 54 HIV-positive people who had received the vaccine and compared results with a control group of 50 HIV-negative people drawn from the larger study. The authors concluded that the COVID-19 vaccines are as effective for PLWH as for people without HIV, but admitted that they could not speculate whether PLWH who had a high viral load or low CD4 count would get the same benefit.
In a South African study that enrolled 104 people with HIV who were on ART and had a viral load below 1,000 copies/mL (most had an undetectable viral load and a median CD4 cell count of 695), researchers found that participants with HIV who had previously had active SARS-CoV-2 infection showed much stronger antibody responses after one dose of the vaccine than participants who had not had COVID-19 did after two doses. But the authors said it shouldn’t be assumed that PLWH with CD4 counts below 500 would have a similar antibody response.
In an Israeli study of 143 people with HIV on ART—95% with an undetectable viral load, and an average CD4 count of 700 for all—researchers found that two doses of the Pfizer vaccine triggered antibody production in 98% of participants, including in the small number of participants with CD4 cell counts below 350.
Another study out of South Africa, however, showed more concerning efficacy results, at least regarding a CoV-2 variant. Published in May in the New England Journal of Medicine, the data showed that, against the variant known as B.1.351 (which first appeared in South Africa), Novavax, Inc’s COVID-19 vaccine had efficacy of 51% among people who were HIV negative, and 43% in a group including HIV-positive participants. Neither the CD4 count nor the viral load of the HIV-positive patients was disclosed, but they were young (median age 32) and “medically stable.” Most cases of COVID-19 were mild or moderate.
Lawrence Corey, M.D., president and director emeritus of Fred Hutchinson Cancer Research Center in Seattle, said variants could complicate the issue, and that the data from the Novavax study—although it’s not known how well-controlled participants’ HIV was—may be cause for concern. “However, there are many people with untreated HIV there,” he said. “This is why we need studies in sub-Saharan Africa of variants. In fact, we need more data globally on HIV and COVID.”
Almost all of the studies on COVID-19 vaccine effectiveness have used antibodies, taken from blood samples. Monica Gandhi, M.D., M.P.H., director of the Gladstone Center for AIDS Research at the University of California San Francisco (UCSF), noted that antibodies are only one way to look at the effectiveness of COVID vaccines.
Gandhi and colleagues recently submitted a grant proposal to the NIH to further explore T-cell responses to COVID-19 in people with HIV. Gandhi and other researchers at UCSF propose an extension of the ongoing LIINC study to determine whether vaccines will be as effective for PLWH with lower CD4 counts versus PLWH with higher CD4 counts over the short and long term, by measuring SARS-CoV-2-specific CD4 and CD8 T-cell responses both at three months and 15 months following complete vaccination.
“Antibodies come from B cells, but T cells are a main way to fight viral infections,” said Gandhi. “I’m interested in the T-cell response, and the vaccine trials show robust T-cell response [from COVID vaccines].”
Do PLWH Need to Take More Precautions, Even if Vaccinated for COVID? Maybe
At a press briefing in May, CDC Director Rochelle Walensky, M.D., M.P.H., said what many Americans hoped to hear: “If you are fully vaccinated, you can start doing the things that you had stopped doing because of the pandemic.” That shift occurred because, according to the agency’s public health guidance, currently authorized vaccines in the U.S. are determined to be “highly effective at protecting vaccinated people against symptomatic and severe COVID-19.”
In its guidance, the CDC is pretty clear about what a vaccinated person can safely do, and what’s risky for an unvaccinated person. But it doesn’t make a special category for vaccinated people who may be immunocompromised, or, specifically, PLWH with low CD4 counts.
However, Philip Chan, M.D., chief medical officer of Open Door Health and consultant medical director at the Rhode Island Department of Health, said PLWH with high viral loads and/or low CD4 counts should: “Keep wearing your mask if CD4 drops below 200, and distance and avoid crowds.” He added that PLWH with low CD4 counts should not worry about effects from COVID vaccines. “They’re not live vaccines, and that makes a difference.”
Corey also drove home the point of getting vaccinated against COVID-19 regardless of CD4 count or viral load, as well as the importance of getting HIV under control. “If your HIV is not suppressed, you are potentially immunocompromised and could transmit a [CoV-2] variant,” he said. “That is the concern.”
Might PLWH need a booster shot to prevent COVID-19? Probably not, as long as HIV is well controlled, according to Gandhi, who published an essay explaining why boosters are unnecessary for most.
“In general, we don’t boost other vaccines [for PLWH], like tetanus, pertussis, regardless of CD4 count, except for people with T cells less than 200,” she said. Gandhi said a booster could be given for the hepatitis B vaccine, however.