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Some ART Formulations Reduce COVID-19 Risk, Hospitalization Rates

A Spanish study determined that HIV patients on some types of antiretroviral therapy appear to have lower risks of COVID-19 and lower hospitalization rates if they get infected. Find out why the researchers believe ARTs should be tested in those with HIV to see if the drugs could provide some protection against novel coronavirus.

MADRID, SPAIN – Does antiretroviral therapy provide some protection from COVID-19 for HIV patients and could it be used to similar effect in those without HIV?

Those are questions posed in a recent Annals of Internal Medicine article. Spanish Ministry of Health-led authors sought describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive individuals receiving ART.

To do that, they conducted a cohort study in the HIV clinics of 60 Spanish hospitals between Feb. 1 and April 15, 2020. Included were 77,590 HIV patients receiving ART.

Focusing on use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), the study team estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction–confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death.

Of 77,590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died.

Results indicate that the risks for COVID-19 diagnosis and hospitalization were greater in men and patients older than 70 years. Researchers calculated the risk for COVID-19 hospitalization at 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens.

The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. The authors point out that no patient receiving TDF/FTC was admitted to the ICU or died.

While the researchers advise that residual confounding by comorbid conditions cannot be completely excluded, they conclude, “HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV.”

The authors reject suggestions that the lower risk for COVID-19 diagnosis among persons receiving TDF/FTC is explained by less intensive testing or other circumstantial evidence. “ Alternatively, another explanation for these findings is that TDF/FTC prevents serious COVID-19 in HIV-positive persons. Molecular docking and other in vitro studies) suggest that NRTIs, such as TDF, TAF, ABC, and 3TC, might be effective against SARS-CoV-2 infection by inhibiting RNAdRNAp,” according to the researchers. “This also might explain the 32% lower risk for COVID-19 diagnosis in persons receiving ABC/3TC compared with those receiving TAF/FTC. Tenofovir diphosphate (TFV-DP) is the common active triphosphate form of TAF or TDF and, because of its smaller size, has been proposed to fit better in the active site of SARS-CoV-2 RNAdRNAp “

“In summary, we took advantage of the overlap between two ongoing pandemics (HIV and SARS-CoV-2) in Spain. Our results suggest that the risk for COVID-19 diagnosis is not higher in HIV-positive persons than in the general population, and that HIV-positive patients receiving TDF/FTC had a lower risk for COVID-19 and related hospitalization than other HIV-positive persons,” the authors write. “These findings warrant further investigation in studies of HIV preexposure prophylaxis and in randomized trials for the treatment and prevention of COVID-19 in persons without HIV.”