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Common HIV medication associated with improved COVID-19 outcomes

Kaiser Permanente research finds benefit both for people receiving HIV treatment and those getting preventive PrEP medication

A medication used to treat HIV and to prevent at-risk people from contracting the virus may improve COVID-19 outcomes for both groups, according to research from Kaiser Permanente published in Clinical Infectious Diseases.

The results could be important for anyone with HIV or at risk of contracting HIV, said senior author Michael J. Silverberg, PhD, MPH, an HIV epidemiologist and research scientist with the Kaiser Permanente Division of Research (DOR). “This knowledge can potentially be used to support ongoing adherence to medication as well as choosing a medication when there are multiple options,” Silverberg said.

Michael Silverberg, PhD, MPH

Tenofovir is a commonly prescribed antiretroviral therapy (ART) medication that reduces the amount of HIV in an HIV-positive person’s blood. Tenofovir is also in 2 of the 3 HIV pre-exposure prophylaxis (PrEP) medication options for people at risk of acquiring HIV infection.

At the beginning of the pandemic, the Centers for Disease Control and Prevention added HIV to its list of conditions that were considered high risk for more serious COVID-19 outcomes. But research since then has been mixed, sometimes showing higher rates of hospitalization and death for people with HIV, sometimes not.

This made researchers wonder: was something in ART medications protective for COVID-19, and did this explain differences in findings? “We were interested in learning more about the potential protection of tenofovir for severe outcomes in people with HIV and whether this potential protective effect extended to people without HIV, who also take the same medications to prevent new HIV infections,” said study lead author Alexandra N. Lea, MPH, a senior research project manager at the Division of Research.

To ensure a large and diverse study group, the researchers used data from the Corona Infectious Virus Epidemiology Team, which includes multiple, selected cohort studies participating in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). The researchers looked at patients aged 18 to 80 who tested positive for SARS-CoV-2, the virus that causes COVID-19, from March 1 to November 30, 2020. A total of 191,136 patients, including 1,785 people with HIV, were included. They analyzed hospitalization and mechanical ventilation outcomes.

Overall, the risk of hospitalization for people with HIV was 31% higher and the risk of mechanical ventilation or death was 51% higher compared with people without HIV. This likely reflects how HIV-associated immunosuppression might increase COVID-19 severity, Lea said.

Alexandra N. Lea, MPH

Tenofovir use seemed to protect against more severe COVID-19 outcomes for both people with and without HIV. The researchers found a 19% reduction in hospitalization for any reason and a 48% reduction in mechanical ventilation or death for people with HIV taking ART with tenofovir compared with those taking ART without tenofovir.

People without HIV taking PrEP with tenofovir were 29% less likely to be hospitalized for any reason and 14% less likely to be hospitalized for COVID-19 than those not taking PrEP.

That the researchers found a protective effect of similar magnitude for both people with and without HIV “further supports the idea that the protective effect of tenofovir is real, rather than an artifact, although further research is needed,” said Silverberg.

“Why tenofovir seems to be protective when other ART medications are not is being investigated,” he added. “Laboratory studies have suggested tenofovir might work through a variety of ways, such as inhibiting the coronavirus’s ability to enter the cell as well as its ability to fuse, replicate, and spread once it has gained entry.”

Potential COVID-19 treatment

The results could eventually have implications for COVID-19 treatment, explained co-author Jacek Skarbinski, MD, a DOR research scientist and infectious disease specialist with The Permanente Medical Group. Just 3 treatment options are FDA-approved for COVID-19. They are available through insurance providers or are free from selected pharmacies with a prescription but may become more expensive in the future, and their effectiveness varies, Skarbinski said.

Jacek Skarbinski, MD.

“One of these, tenofovir disoproxil fumarate, is already widely available in a low-cost, generic version and might serve as an additional, accessible treatment option for individuals at risk for severe COVID outcomes if the suggestive findings in this study can be confirmed in well-designed, randomized controlled trials,” he said.

The NA-ACCORD study group includes researchers from Kaiser Permanente Northern California, Kaiser Permanente Mid-Atlantic States, Vanderbilt University, University of North Carolina, the National U.S. Veterans Affairs Healthcare System, and the MACS/WIHS Combined Cohort Study.

Additional co-authors were Wendy A. Leyden, MPH, Oleg Sofrygin, PhD, and Ben J. Marafino, PhD, from the Division of Research; and Michael A. Horberg, MD, MAS, and Celeena Jefferson, MIT, from the Kaiser Permanente Mid-Atlantic Permanente Research Institute. For a full list of co-authors, see the study.

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. It seeks to understand the determinants of illness and well-being, and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 450 epidemiological and health services research projects. For more information, visit or follow us @KPDOR.

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