The Perfect Enemy | Study sees possible benefit of tenofovir against COVID-19, but questions remain - Healio
April 12, 2024

Study sees possible benefit of tenofovir against COVID-19, but questions remain – Healio

Study sees possible benefit of tenofovir against COVID-19, but questions remain  Healio

March 11, 2023

3 min read

Lea and del Amo report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Key takeaways:

  • Studies have identified people with HIV as being at higher risk for severe COVID-19 outcomes.
  • An analysis of patients with SARS-CoV-2 infection found that people taking tenofovir for HIV treatment or prevention were at lower risk for severe COVID-19 outcomes.
  • The protective effect of tenofovir against severe COVID-19 is “biologically plausible” but requires a randomized clinical trial to confirm.

An analysis of COVID-19 outcomes among people being treated for HIV or taking PrEP for HIV prevention found that the HIV medication tenofovir was associated with a lower rate of clinical events, suggesting a protective effect.

The study also found, as some others have, that severe COVID-19-related outcomes were more common among people with HIV than the general population before the rollout of COVID-19 vaccines.


Data derived from Lea AN, et al. Clin Infect Dis. 2023;doi:10.1093/cid/ciad084.

In the study, people on ART containing tenofovir and people without HIV who were taking PrEP containing the drug were less likely to be hospitalized for any reason and less likely to need mechanical ventilation or die, according to results published in Clinical Infectious Diseases.

“Computer simulation models suggest that tenofovir may inhibit [SARS-CoV-2’s] capacity for cell entry and for fusion, replication and spread, while in vitro studies of animal cells indicated that tenofovir inhibits the release of the SARS-CoV-2 viral genome, and an in vivo study in ferrets found a reduction in severity and shorter duration of clinical symptoms,” Alexandra N. Lea, MPH, senior research project manager at Kaiser Permanente, and colleagues wrote, noting that their findings are consistent with other analyses, reviews and trials.

“Thus, there is evidence of a potential causal protective effect of tenofovir-based therapy against adverse COVID-19 outcomes,” they wrote.

For the analysis, Lea and colleagues analyzed data on 191,136 patients with COVID-19 treated in the Kaiser Permanente health system between March 1, 2020, and Nov. 30, 2020, including 1,785 people with HIV. Among the people with HIV, 1,139 were prescribed tenofovir, including 1,035 on tenofovir alafenamide (TAF) only, 401 on tenofovir-sparing ART and 245 were not on ART in the previous year. There were also 459 people using PrEP containing tenofovir.

Among people with HIV, 24% were hospitalized, 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, whereas 9% of people without HIV were hospitalized, 6% were hospitalized for COVID-19 and 2% received mechanical ventilation or died.

For people with HIV using tenofovir, 20% were hospitalized, 13% were hospitalized for COVID-19 and 3% received mechanical ventilation or died compared with people with HIV who were not using tenofovir, among whom 31% were hospitalized, 18% were hospitalized for COVID-19 and 8% received mechanical ventilation or died.

Similarly, for people using PrEP, 3% were hospitalized, 3% were hospitalized for COVID-19 and 1% received mechanical ventilation or died compared with people not on PrEP, among whom 8% were hospitalized, 5% were hospitalized for COVID-19 and 1% received mechanical ventilation or died.

Overall, the researchers report a 19% reduction in hospitalization for people with HIV taking tenofovir and 48% reduction in mechanical ventilation or death, as well as 29% reduction in hospitalizations for PrEP users.

“Tenofovir use appeared to confer protection against more severe COVID-19 outcomes irrespective of HIV status,” the researchers concluded.

The analysis included people taking both forms of tenofovir — tenofovir disoproxil fumarate (TDF) and the newer formulation, TAF, both in combination with emtricitabine (FTC).

In a related commentary, Julia del Amo, MD, PhD, epidemiologist in the Spanish Ministry of Health’s Division for HIV, STIs, Viral Hepatitis and TB control, said previous research has shown protective effects for TDF/FTC but not TAF/FTC among people with SARS-CoV-2 infection.

A protective effect of tenofovir “has been consistently reported for TDF/FTC compared to TAF/FTC and to other regimens” for HIV, del Amo wrote.

“The protective effect of TDF is biologically plausible,” she wrote, noting that simulated “and some in vitro studies suggest tenofovir partly inhibits the SARS-CoV-2 RNA-dependent RNA-polymerase.”

Even so, del Amo said the exact mechanism of action of tenofovir against SARS-CoV-2 is unknown and, despite supportive evidence in animal models and smaller trials, some of the conclusions being put forward are “speculative as the definitive randomized clinical trial has not been conducted.”

Additionally, del Amo pointed out that people who take ART or PrEP “are not a random group of the general population,” but rather have HIV or are at higher risk for acquiring HIV — in addition having a higher risk for COVID-19.

“The question of whether TDF/FTC provides protection against clinical severity of COVID-19 remains unanswered. This article provides less convincing data that TAF/FTC may reduce COVID-19 clinical severity, but collaborative analyses of cohorts with large numbers of people with HIV on different ART regimens and from different parts of the world, before and after COVID-19 vaccination, would help to disentangle these intriguing associations,” del Amo wrote.

“Collaborative analyses of PrEP cohorts comparing TAF/FTC and TDF/FTC users may very be helpful too; so would be collaborations of cohorts of persons with chronic hepatitis B infection,” she wrote. “The definitive answer, though, should come from [a randomized clinical trial].”