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

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.