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

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).

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.