Estimation of prevention-effective CAB-LA concentrations among men who have sex with men (MSM) and transgender women (TGW) in HPTN 083

Brett Hanscom, Fred Hutch Cancer Center, 1100 Fairview Ave E, Seattle, WA 98109, USA.
Mark A. Marzinke, John Hopkins University, Baltimore, MD, USA.
Xinnong Li, University of Buffalo, Buffalo, NY, USA.
Deborah Donnell, Fred Hutch Cancer Center, 1100 Fairview Ave E, Seattle, WA 98109, USA.
Robert Bies, University of Buffalo, Buffalo, NY, USA.
Craig W. Hendrix, John Hopkins University, Baltimore, MD, USA.
Zhe Wang, Fred Hutch Cancer Center, 1100 Fairview Ave E, Seattle, WA 98109, USA.
Carolina Acuipil, ViiV Healthcare, Durham, NC, USA.
Alex Rinehart, ViiV Healthcare, Durham, NC, USA.
Jon W. Collins, ViiV Healthcare, Durham, NC, USA.
James F. Rooney, Gilead Sciences, Foster City, CA, USA.
Lydia Soto Torres, NIH Division of AIDS, Bethesda, MD, USA.
Paul Richardson, John Hopkins University, Baltimore, MD, USA.
Suwat Chariyalerstsak, Chang Mai University, Chang Mai, Thailand.
Jose Valdez Ramalho Madruga, Secretarial of Health, Sao Paulo, Brazil.
Christopher B. Hurt, Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Manya Magnus, George Washington University, Milken Institute School of Public Health. Washington DC, USA.
Ian Frank, University of Pennsylvania, Division of Infectious Diseases, Philadelphia, PA, USA.
Marybeth McCauley, Family Health International (FHI 360), Washington, DC, USA.
Beatriz Grinsztejn, Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation, Rio ds Janeiro, Brazil.
Raphael J. Landovitz, CARE Center, University of California Los Angeles, Los Angeles, CA, USA.

Document Type

Journal Article

Publication Date

11-5-2025

Journal

The Journal of infectious diseases

DOI

10.1093/infdis/jiaf561

Keywords

Cabotegravir; Cabotegravir Pharmacokinetics; HIV PrEP; HPTN 083; Long-acting PrEP

Abstract

BACKGROUND: 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. METHODS: We conducted a nested case-control study among HPTN 083 participants 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 (1x PA-IC90) and 4x PA-IC90. HIV risk was modeled using conditional logistic regression. RESULTS: Plasma CABmin was ≥4x PA-IC90 in 26% of HIV-positive cases, compared to 76% of matched controls. Plasma CABmin ≥4x PA-IC90 was associated with a 93% reduction in risk of HIV acquisition compared to CABmin <1x PA-IC90 (95% CI: 76%, 98%, p<0.001). CABmin between 1x and 4x PA-IC90 had an estimated risk reduction of 79% compared to CABmin <1x PA-IC90 (95% CI: -19%, 96%, p=0.07). CONCLUSIONS: Consistent plasma CAB concentrations ≥4x PA-IC90 were estimated to provide 93% protection against HIV in MSM and TGW.

Department

Epidemiology

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