Estimation of Prevention-Effective CAB-LA Concentrations Among Men Who Have Sex With Men (MSM) and Transgender Women (TGW) in HPTN 083.

Abstract

The HIV Prevention Trials Network (HPTN) 083 Trial demonstrated the superiority of long-acting, injectable cabotegravir (CAB) over daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis among cisgender men (MSM) and transgender women (TGW) who have sex with men. Plasma CAB concentrations associated with HIV protection in humans are unknown. We conducted a nested case-control study to investigate the association between plasma CAB concentrations and HIV risk. Plasma CAB concentrations were estimated for participants with confirmed HIV and for HIV-negative controls, who were matched on region, gender, and race. The window of HIV acquisition for cases was defined as the time between the last HIV-negative visit and the first HIV-positive visit; this window was used to evaluate CAB exposure for cases and their matched controls. Participants were categorized by the minimum estimated CAB concentration (CABmin) during this window relative to the protein-adjusted 90% CAB inhibitory concentration (1× PA-IC90) and 4× PA-IC90. HIV risk was modeled using conditional logistic regression. Plasma CABmin was ≥4× PA-IC90 in 26% of HIV-positive cases, compared with 76% of matched controls. Plasma CABmin ≥4× PA-IC90 was associated with a 93% reduction in risk of HIV acquisition compared with CABmin <1× PA-IC90 (95% CI: 76%, 98%, P < .001). CABmin between 1× and 4× PA-IC90 had an estimated risk reduction of 79% compared with CABmin <1× PA-IC90 (95% CI: -19%, 96%, P = .07). Consistent plasma CAB concentrations ≥4× PA-IC90 were estimated to provide 93% protection against HIV in MSM and TGW.