Savic reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Women at high risk for HIV need higher levels of plasma tenofovir to prevent infection compared with men, according to data from the largest HIV pharmacokinetics database to date.
“While daily tenofovir-based PrEP has shown efficacy in decreasing incident HIV infections in populations at risk for HIV infection, the protective level of tenofovir associated with prevention is not known,” Radojka M. Savic, PhD, professor of bioengineering at the University of California San Francisco, told Healio.
Savic said adherence to PrEP is “imperfect and varies between populations, and although daily adherence is recommended, controversies exist regarding PrEP efficacy in different populations considering different levels of adherence.”
“Therefore, we thought of pooling and integrating available individual data from several clinical trials, using innovative computational approaches, to answer these questions,” Savic said.
Savic and colleagues assessed pooled data from 2,950 people enrolled in three phase 3 trials — iPrEx, VOICE and Partners PrEP. They created individual specific risk scores for acquiring HIV and analyzed longitudinal tenofovir (TFV) pharmacokinetics, HIV outcomes, individual risk scores and the effect of sex at birth.
Savic and colleagues used modeling to estimate that around 50% of people were adherent to PrEP lower than participants’ self-reported adherence, which was around 90%, according to the study. The study also demonstrated that the estimated protective TFV trough concentration was substantially higher among high-risk women (45.8 ng/mL) compared with high-risk men (16.1 ng/mL) and low-risk individuals in general (approximately 7.5 ng/mL).
Based on these data, Savic said they determined that women at high risk for infection need higher plasma tenofovir levels to prevent HIV compared with men.
“Patient-centric management strategies are needed to improve adherence patterns with daily dosing in those individuals at high risk for HIV infection, paying particular attention to women at high risk,” Savic said. “In addition, these types of models can also be used to develop clinical trial simulation tools to propose novel PrEP formulations, regimens and study designs.”