Modeling the Probability of HIV Infection over Time in High-Risk Seronegative Participants Receiving Placebo in Five Randomized Double-Blind Placebo-Controlled HIV Pre-Exposure Prophylaxis Trials: A Patient-Level Pooled Analysis

Maria Garcia-Cremades; Craig W Hendrix; Priya Jayachandran; Natasha Strydom; Leah Jarlsberg; Robert Grant; Connie L Celum; Michael Martin; Jared M Baeten; Jeanne Marrazzo; Peter Anderson; Kachit Choopanya; Suphak Vanichseni; David V Glidden; Radojka M Savic

doi:10.3390/pharmaceutics14091801

Modeling the Probability of HIV Infection over Time in High-Risk Seronegative Participants Receiving Placebo in Five Randomized Double-Blind Placebo-Controlled HIV Pre-Exposure Prophylaxis Trials: A Patient-Level Pooled Analysis

Pharmaceutics. 2022 Aug 27;14(9):1801. doi: 10.3390/pharmaceutics14091801.

Authors

Maria Garcia-Cremades¹, Craig W Hendrix², Priya Jayachandran¹, Natasha Strydom¹, Leah Jarlsberg¹, Robert Grant³, Connie L Celum⁴, Michael Martin^{5

6}, Jared M Baeten⁴, Jeanne Marrazzo⁷, Peter Anderson⁸, Kachit Choopanya⁹, Suphak Vanichseni⁹, David V Glidden¹⁰, Radojka M Savic¹

Affiliations

¹ Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94143, USA.
² Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
³ Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
⁴ Departments of Global Health, Medicine, and Epidemiology, University of Washington, Seattle, WA 98104, USA.
⁵ Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Atlanta, GA 30333, USA.
⁶ Thailand Ministry of Public Health-US CDC Collaboration, Nonthaburi 11000, Thailand.
⁷ Division of Infectious Diseases, University of Alabama at Birmingham Medical Center, Birmingham, AL 35294, USA.
⁸ Department of Pharmaceutical Sciences, University of Colorado, Denver, CO 80045, USA.
⁹ Bangkok Tenofovir Study Group, Bangkok 10600, Thailand.
¹⁰ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA.

Abstract

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk.

Keywords: HIV prevention trials; key and vulnerable populations; modeling; risk factors; risk phenotypes.

Abstract

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