Tenofovir Disoproxil Fumarate/Emtricitabine and Severity of Coronavirus Disease 2019 in People With HIV Infection

Julia Del Amo; Rosa Polo; Santiago Moreno; Esteban Martínez; Alfonso Cabello; José Antonio Iribarren; Adria Curran; Juan Macías; Marta Montero; Carlos Dueñas; Ana I. Mariño; Santiago Pérez de la Cámara; Asuncion Díaz; José Ramón Arribas; Inma Jarrín; Miguel A. Hernán


AIDS. 2022;36(15):2171-2179. 

In This Article

Abstract and Introduction


Background: Effective, safe, and affordable antivirals are needed for coronavirus disease 2019 (COVID-19). Several lines of research suggest that tenofovir may be effective against COVID-19, but no large-scale human studies with appropriate adjustment for comorbidities have been conducted.

Methods: We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4+ cell count, HIV-RNA viral-load, comorbidities and the following outcomes: laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting.

Results: Of 51 558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% confidence interval) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88–6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals.

Discussion: Compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.


Much research has focused on the repurposing of antivirals for the treatment and prevention of severe COVID-19. Remdesivir, originally developed against the Ebola virus, and molnupiravir, originally developed against the influenza virus, are now used to reduce the risk of hospitalization in high-risk individuals with recently diagnosed coronavirus disease 2019 (COVID-19).[1–5] More research is needed to determine whether tenofovir, an affordable oral drug with a proven safety record, also prevents severe COVID-19.

Among HIV-positive individuals, two observational studies found lower risk of COVID-19 hospitalization[6] and COVID-19 mortality[6,7] among users of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) than among users of other antiretroviral regimes. Another observational study found a lower risk of severe COVID-19 in patients with chronic hepatitis B virus (HBV) infection treated with TDF/FTC than among those treated with entecavir.[8] More recently, a large study in male U.S. veterans with HIV has reported that the risk of COVID-19-related hospitalization for TDF/FTC was less than half the risk for other antiretrovirals).[9] Careful adjustment for clinical characteristics, including those associated with risk of severe COVID-19 (e.g. renal disease), had little impact on the association between TDF/FTC and lower risk of severe COVID-19. However, this study included only men with an average age of 59 years.

These findings suggest that TDF/FTC might be used as preexposure prophylaxis or early treatment of COVID-19.[10,11] This would be especially important for immunosuppressed patients for whom vaccines have suboptimal effectiveness and for individuals for which safety concerns arise with other drugs.

Here, we report the findings from a nationwide cohort study of TDF/FTC and COVID-19 outcomes among men and women of all ages with HIV and on antiretroviral therapy.