Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jul 1;17(4):213-221.
doi: 10.1097/COH.0000000000000746.

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

Urvi M Parikh  1 , John W Mellors
Affiliations
Review

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

Urvi M Parikh et al. Curr Opin HIV AIDS. .

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.

PubMed Disclaimer

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.

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
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Koss CA, Havlir DV, Ayieko J, Kwarisiima D, Kabami J, Chamie G, et al. HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda. PLoS Med. 2021;18(2):e1003492. - PMC - PubMed

    2. This large population-based PrEP study in rural Kenya and Uganda described virologic outcomes following seroconversion on TDF/FTC PrEP

    1. Hojilla JC, Hurley LB, Marcus JL, Silverberg MJ, Skarbinski J, Satre DD, et al. Characterization of HIV Preexposure Prophylaxis Use Behaviors and HIV Incidence Among US Adults in an Integrated Health Care System. JAMA Netw Open. 2021;4(8):e2122692. - PMC - PubMed
    1. Shover CL, Shoptaw S, Javanbakht M, Lee SJ, Bolan RK, Cunningham NJ, et al. Mind the gaps: prescription coverage and HIV incidence among patients receiving pre-exposure prophylaxis from a large federally qualified health center in Los Angeles, California : Mind the Gaps: Cobertura de recetas e incidencia de VIH entre pacientes recibiendo profilaxis pre-exposicion de un centro de salud grande y federalmente calificado en Los Angeles, CA. AIDS and behavior. 2019;23(10):2730–40. - PMC - PubMed
    1. Volk JE, Marcus JL, Phengrasamy T, Blechinger D, Nguyen DP, Follansbee S, et al. No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting. Clin Infect Dis. 2015;61(10):1601–3. - PMC - PubMed
    1. The Lancet HIV. New PrEP formulation approved…but only for some. Lancet HIV. 2019;6(11):e723. - PubMed

Publication types