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. 2025 May 12;12(6):ofaf285.
doi: 10.1093/ofid/ofaf285. eCollection 2025 Jun.

Early Virologic Success on Antiretroviral Therapy Among Individuals With Breakthrough HIV Acquisition on Long-Acting Cabotegravir Pre-exposure Prophylaxis

Urvi M Parikh  1 , Monica Gandhi  2 , Jessica Altamirano  3 , Hussein Safa  4 , Aniruddha Hazra  5 , Lisa Georgetti Gomez  2 , Prerak Shukla  3 , Trevor Hedberg  6 , Amy L Heaps  1 , Elias K Halvas  1 , Karen Kuncze  2 , Hideaki Okochi  2 , Charles Walworth  7 , Amy Conroy  2 , Chris Bositis  2 , Carolyn Chu  2 , John W Mellors  1 , Catherine A Koss  2
Affiliations

Early Virologic Success on Antiretroviral Therapy Among Individuals With Breakthrough HIV Acquisition on Long-Acting Cabotegravir Pre-exposure Prophylaxis

Urvi M Parikh et al. Open Forum Infect Dis. .

Abstract

HIV-1 breakthrough on long-acting cabotegravir (CAB-LA) for HIV prevention is rare but could impact viral suppression on integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART). We report the first study of ART outcomes following CAB-LA breakthrough during routine clinical care. Three individuals acquired HIV-1 on CAB-LA despite on-time injections; 2 had low-frequency major INSTI resistance mutations. All started darunavir-based ART; 1 subsequently switched to bictegravir-based ART. All maintained plasma HIV-1 RNA <50 copies/mL through ≥5 months post-ART initiation, providing early evidence of virologic success with standard ART regimens and paving the way for longer-term studies on optimal ART after CAB-LA breakthrough.

Keywords: HIV drug resistance (HIVDR); antiretroviral therapy (ART); integrase strand transfer inhibitors (INSTIs); long-acting cabotegravir (CAB-LA); pre-exposure prophylaxis (PrEP).

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Conflict of interest statement

Potential conflicts of interest. U.M.P. serves as a consultant to Merck and has received a speaker's honorarium from Thermo Fisher in the past, separate from this work. J.A. reports honoraria for Gilead Sciences and ViiV Healthcare speaker’s bureau. A.H. reports contracts for clinical research unrelated to this work from Gilead Sciences and consulting fees from Gilead Sciences, ViiV Healthcare, and Abbott Technologies. H.O., A.C., and M.G. report research grant support from the National Institutes of Health. C.W. is an employee of Labcorp and owns Labcorp stock. C.C. is a volunteer member of the Board of Directors of the American Academy of HIV Medicine. J.W.M. is a consultant to Gilead Sciences, Inc., and has received grant funding from Gilead Sciences, Inc., to the University of Pittsburgh (unrelated to the current work) and receives compensation from Galapagos NV, Infectious Disease Connect, Inc., and MingMed Biotechnology Co., Ltd. (unrelated to the current work). C.A.K. reports research grant support to her institution from the National Institutes of Health and Gilead Sciences. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Antiretroviral treatment outcomes and HIV-1 drug resistance profiles in 3 individuals who acquired HIV-1 after long-acting cabotegravir pre-exposure prophylaxis. For all 3 participants, antiretroviral regimens are depicted above the HIV-1 test results as follows: all individuals had pre-exposure prophylaxis (PrEP) with long-acting cabotegravir (CAB-LA); Participants 001A and 002A switched to the antiretroviral (ART) regimen cobicistat-boosted darunavir/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF); Participant 003A had no regimen for 12 d post-HIV detection, then started DRV/c/F/TAF, and switched to bictegravir/F/TAF. Point-of-care or commercial laboratory–based HIV-1 antibody/antigen (Ab/Ag) diagnostic test results are indicated as negative or reactive, and commercial HIV-1 RNA results are reported as copies/mL in nonbold text. Research laboratory testing (in bold) was done by quantitative polymerase chain reaction single-copy assay with a detection limit of 1 RNA copy/mL, and INSTI-associated mutations were identified in plasma HIV RNA using single-genome sequencing of full-length integrase. The proportion presented is the number of sequences with the noted mutation over the total number of genomes sequenced.
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References

    1. Marzinke MA, Fogel JM, Wang Z, et al. Extended analysis of HIV infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. Antimicrob Agents Chemother 2023; 67:e0005323. - PMC - PubMed
    1. Parikh UM, Koss CA, Mellors JW. Long-acting injectable cabotegravir for HIV prevention: what do we know and need to know about the risks and consequences of cabotegravir resistance? Curr HIV/AIDS Rep 2022; 19:384–93. - PMC - PubMed
    1. Department of Health and Human Services, Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2024. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv. Accessed October 17, 2024.
    1. Gandhi RT, Landovitz RJ, Sax PE, et al. Antiretroviral drugs for treatment and prevention of HIV in adults: 2024 recommendations of the International Antiviral Society-USA Panel. JAMA 2025; 333:609–28. - PubMed
    1. World Health Organization . Guidelines on Long-Acting Injectable Cabotegravir for HIV Prevention. World Health Organization; 2022. Available at: https://www.who.int/publications/i/item/9789240054097. Accessed September 17, 2024. - PubMed