Each of the past three weeks has brought encouraging news about the efficacy of a coronavirus vaccine candidate. But given the complexities involved with distribution, most experts agree that even if these and other vaccines are approved for use, it could be six months at least before they’re widely available in the U.S.
Given the nation’s rapid descent into COVID hell, plus the Trump administration’s lack of a coordinated response (effectively encouraging the novel coronavirus to rampage from coast to coast), the few approved treatments we have for COVID-19 are our best hope of preventing severe illness and death for the hundreds of thousands of Americans likely to become infected over the next several months.
People living with HIV (PLWH) and their health care providers may have some concern about interactions between HIV treatments and COVID-19 treatments. Here’s what we know right now.
How Experts Are Monitoring Potential Issues With COVID-19 Treatments Among People Living With HIV
In the U.S., the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), which is funded by the National Institutes of Health, has a team operating across existing HIV research centers to study drug interactions among 15,000 PLWH. This team is looking at interactions between currently approved COVID-19 medications and antiretrovirals used to treat HIV.
On a larger scale, CNICS is integrating and analyzing the medical records of more than 35,000 people in an attempt to more generally complete the puzzle of understanding COVID-19 risks among PLWH. They’re examining what the risks of complications are for PLWH who contract COVID-19, whether people with HIV face a higher risk of death from COVID-19, and what factors could put PLWH at risk of serious illness or death.
Globally, the Liverpool Drug Interaction Group has a comprehensive website detailing drug interactions with experimental COVID-19 therapies, but the data are still limited.
To learn more, we consulted two physicians who lead a CNICS team that tracks records of PLWH who also have COVID-19: Edward “Lalo” Cachay, M.D., a professor of medicine at the University of California, San Diego, and Adrienne Shapiro, M.D., Ph.D., an infectious diseases specialist at the University of Washington. Both warned that not enough data are available to make any definitive statements, but they did have some wisdom to share based on what we know to date.
What We Know About Specific COVID-19 Treatments in People Living With HIV
In October, the U.S. Food and Drug Administration (FDA) formally approved remdesivir—which is sold under the brand name Veklury—to treat COVID-19. Although studies show the drug’s effectiveness is mixed—for instance, one notable study showed the drug can shorten hospital time, while another showed a failure to prevent deaths—it is nonetheless the only antiviral drug currently authorized for treatment of COVID-19.
There are no data on remdesivir’s interaction with antiretroviral treatments for HIV. However, remdesivir is metabolized through the liver, which could be an issue for people taking antiretrovirals. “Perhaps the most crucial limitation of remdesivir in PLWH is that it can increase liver enzymes and cannot be administered to patients with advanced kidney disease when renal function is below 30%,” Cachay said, noting that both conditions are present in many PLWH.
In August, the World Health Organization noted a very high number of liver and kidney problems in patients receiving the drug. The European Medicines Agency (EMA) is reviewing reports of kidney injuries in some patients taking remdesivir.
In cases where Cachay prescribes remdesivir to a PLWH, he says, “I personally will avoid using HIV medications with a strong induction potential; for example, some NNRTIs such as efavirenz or etravirine. Strong inducers will lower the levels of remdesivir. On the other hand, there is the potential that some protease inhibitors can increase levels of remdesivir and its metabolites, but it is unknown its clinical significance.”
Shapiro agrees with Cachay on not using remdesivir to treat anyone with decreased kidney function. In addition, “Doctors treating patients with COVID-19 and HIV should also consult an infectious disease specialist at the hospital,” she said.
Powerful corticosteroids such as dexamethasone have been shown to prevent an overreaction of the body’s immune system—referred to as a “cytokine storm”—which can lead to some of the most severe outcomes of COVID-19. Studies have shown that dexamethasone reduces the risk of death by about 30% for people on ventilators.
As with remdesivir, the data just aren’t there yet regarding potential interactions between corticosteroids and HIV medications. But Cachay speculated that dexamethasone, when used for a short time at a low dose, should not result in negative interactions with antiretrovirals. “Prolonged use of dexamethasone can theoretically favor the induction of liver CYP enzymes,” he said. “But, clinically, I would not be too concerned when dexamethasone is used for less than two weeks.”
In August, the FDA authorized use of convalescent plasma—blood plasma from patients who have recovered from COVID-19—to treat people who are currently experiencing severe symptoms. The idea is that the antibodies from these individuals can kick-start the immune systems of people who are ill with COVID-19.
Though the Trump administration touted convalescent plasma as a “major therapeutic breakthrough,” there are still not enough data from randomized controlled trials to back up that optimistic assessment.
For PLWH on HIV treatment, there are no known medical interaction issues, nor are there contraindications regarding renal or liver function, both Cachay and Shapiro said. “We know from the Mayo Clinic study that it is safe to transfuse, but [we urgently need] to establish its efficacy role,” Cachay said. “We are eagerly waiting for the Johns Hopkins randomized clinical trials from post-exposure prophylaxis and early treatment of COVID-19 patients.”
Monoclonal Antibody Therapy
On Nov. 21, the FDA granted emergency use authorization for an antibody cocktail, casirivimab and imdevimab, to be used as treatment in mild to moderate cases of COVID-19. This follows the FDA’s emergency use authorization on Nov. 9 for another monoclonal antibody therapy, bamlanivimab.
Casirivimab/imdevimab was given to President Trump in October when he was hospitalized for COVID-19 and is thought by some to have sped his recovery.
Monoclonal antibodies are developed in laboratories, but they mimic those produced in the human body to stimulate a patient’s immune system and block the novel coronavirus from entering its target cells. The therapy has also had success in treating Ebola, although the treatments are very expensive and their availability is limited.
This drug class is already well-known within HIV treatment research circles. In 2018, the FDA approved the monoclonal antibody ibalizumab (Trogarzo) as treatment for HIV in people who are resistant to most existing antiretrovirals. Since it is taken as a once-every-two-weeks injection, it can also reduce the pill burden associated with current antiretroviral treatments. Several other monoclonal antibodies for HIV are in development.
Because monoclonal antibodies are already known to be an effective alternative therapy for people with HIV, it doesn’t appear likely that using other monoclonal antibodies for COVID-19 would negatively impact people on antiretrovirals, or people taking ibalizumab. Researchers at CNICS will also be looking at this treatment’s interaction with HIV meds once more data are available.
Although President Trump relentlessly hyped this immunosuppressive drug, which has been used for years to treat malaria, as a miracle cure for COVID-19, there is no evidence that it’s helpful. The FDA granted, but then quickly revoked, an emergency use authorization for hydroxychloroquine to treat COVID-19, and now the agency says it could do more harm than good.
Can HIV Medications Protect Against Severe COVID-19 Outcomes?
Early in the COVID crisis, there was some hope that current HIV meds could work against COVID-19 and thus prevent the most severe health outcomes. The hypothesis was that, since several widely prescribed anti-HIV medications (including the protease inhibitors darunavir [Prezista], lopinavir/ritonavir [Kaletra], and tenofovir/emtricitabine [Truvada]) appeared likely to block the critical RNA polymerase of SARS-CoV-2—and because those drugs were structurally related to remdesivir—they may be able to suppress SARS-CoV-2 replication in those who take it.
But this initial promise has not panned out, at least so far. An initially promising study involving tenofovir/emtricitabine was dismissed by experts due to a small sample size, and it has not been replicated on a larger scale. And hopes of repurposing lopinavir/ritonavir were dashed as studies observing its ability to suppress SARS-CoV-2 replication in the setting of severe disease showed no beneficial effect.
Cachay said that there still might be positive results from ongoing research, but stressed that the primary value of antiretroviral therapy appears to be non-specific: Rather than blocking SARS-CoV-2 directly, the ability of modern HIV medications to keep HIV suppressed results in a healthier immune system that is more capable of fighting off COVID-19. “Preliminary research from CNICS is observing that having suppressed viremia matters to avoid COVID-19 complications,” Cachay said. “Certainly, there is no evidence to recommend that our patients need to be taking certain HIV regimens to prevent COVID-19.”
The Bottom Line on COVID-19 Care for People on HIV Treatment
The biggest potential risks for interactions with COVID-19 treatments and HIV treatments are those for renal and liver functions. But until the data are in, this remains only a potential concern. Meanwhile, Shapiro says the biggest danger a PLWH will typically face if they get COVID-19 is the danger associated with an unsuppressed HIV viral load.
“If a patient has COVID-19 and HIV, they should be given indicated treatments for COVID, and get viral load for HIV suppressed. During COVID or any time, it’s important to suppress viral load, which can help fight off COVID infection,” she said.
Shapiro brought up another complication for PLWH during the COVID crisis, one that might worsen as new cases continue to rise: isolation affecting their access to care. “As more people are encouraged to stay home and use telemedicine, it’s important that they’re able to access [their antiretrovirals].”
Similarly, HIV-negative people “need resources for testing and case notification,” she added. For people who don’t know their status, HIV self-testing kits, some of which can be purchased online, could be a helpful alternative to in-person testing during the COVID crisis.
Cachay said it’s also important for care providers to counsel PLWH about COVID-19 related stress, anxiety, “and among some, PTSD-like feelings due to the internalized stigma associated with the AIDS isolation in the 1980s.”
And, of course, both Cachay and Shapiro advise that PLWH continue to do what experts say we all need to be doing: socially distance and wear masks.