How could HIV-1 drug resistance impact preexposure prophylaxis for HIV prevention?

Urvi M Parikh, John W Mellors, Urvi M Parikh, John W Mellors

Abstract

Purpose of review: To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs).

Recent findings: The greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy.

Summary: PrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.

Conflict of interest statement

Conflicts of Interest.

U.M.P. reports consulting agreements from Merck. J.W.M. reports consulting agreements from Gilead Sciences, Inc. and Infectious Disease Connect, and shares/share options from Infectious Disease Connect, Cocrystal Pharma, Inc., and Abound Bio, outside the submitted work.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
Risk of HIV Drug Resistance from Pre-Exposure Prophylaxis and Antiretroviral Therapy with the Same Drugs and Drug Classes * In December 2021, islatravir development had been paused due to safety concerns.
Figure 2.
Figure 2.
Percentage (%) of Seroconversions with NNRTI Resistance from the Dapivirine Ring and Placebo Arms of Phase III and Open-Label Studies of Dapivirine Ring DPV = dapivirine ring arm; PLB = placebo ring arm

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Source: PubMed

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