Urvi M Parikh1, Brenda Hoagland2, Jana L. Jacobs1, Carolina Coutinho2, Marcos Benedetti2, Dianna L. Hoeth1, Asma Naqvi1, Amy L. Heaps1, Kerri J. Penrose1, John W. Mellors1, Sandro Nazer2, Roberta Trefiglio2, Raphael J. Landovitz3, Valdiléa G. Veloso2, Beatriz Grinsztejn2, and the ImPrEP Study Team

1University of Pittsburgh, Pittsburgh, Pennsylvania, USA; 2 Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 3University of California Los Angeles, Los Angeles, California, USA

Introduction: HIV acquisition during long-acting cabotegravir (CAB) PrEP is rare but poses significant challenges for HIV detection and monitoring within prevention programs. We present the first analysis of HIV-1 acquisitions on CAB PrEP in routine public health settings in Brazil.

Methods: ImPrEP CAB Brasil is an implementation study of same‐day CAB initiation at oral PrEP clinics across 6 Brazilian cities. Individuals aged 18–30 years are enrolled after negative rapid antibody (Ab)-only diagnostic tests (RDT) and undetectable HIV-1 RNA GeneXpert; HIV-1 RNA (Roche COBAS), Ab/Ag RDT and 4^th gen Abbott Architect are performed retrospectively. Geenius is performed with any positive test result. Research testing includes BioPlex 2200 HIV Ag-Ab, HIV-1 RNA single copy assay (SCA; LOD ≥1 c/mL), and quantitation of cell-associated LTR DNA (CAD). Plasma HIV-1 RNA mutations are identified by single or whole genome sequencing (SGS/WGS) of full-length integrase.

Results: Among 1220 participants (ppt) enrolled in the ImPrEP incidence cohort between 11/2023-9/2024, 4 HIV-1 acquisitions occurred on CAB (all MSM, ages 19–25). • Ppt A: HIV-1 RNA retrospectively detected at CAB initiation (<20 cp/mL); not detected by SCA, repeat RNA – CAD not detected (in 1×106 buffy coat cells) until M1 – RDT reactive at month 9 post-CAB initiation • Ppt B, C: HIV-1 RNA 1.9 – 655 at time of detection – CAD detected (in 11 – 343 cp/5×106 buffy coat cells) – RDT non-reactive at time of HIV diagnosis; retrospectively found to be reactive by BioPlex, Architect, and/or Geenius • Ppt D: HIV-1 RNA detected 13 months after CAB initiation and no subsequent injections.

Conclusions: Among 4 CAB-LA PrEP users in Brazil who acquired HIV-1, 3 had HIV-1 RNA <1000 c/mL at diagnosis, and delayed Ab detection (2-9 months after first detectable RNA). • Major INSTI mutations were observed only in 1 individual despite continued use of CAB prior to HIV confirmation. • These findings confirm CAB’s high efficacy for PrEP and the rarity of breakthrough infections, while underscoring the need for sensitive point-of-care diagnostics and additional data on responses to INSTI-based ART in such clinical scenarios.