Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine (FTC)-based pre-exposure prophylaxis (PrEP) were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays for TFV, which examine short-term adherence, are in development. However, the ability of poor short-term and long-term adherence to predict future PrEP nonretention is unknown.
Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project.
An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study nonretention.
Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By the end of study, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating suboptimal long-term adherence (TFV-DP <700 fmol/punch). The strongest factor associated with future study nonretention using a binary drug-level cut-off was an undetectable DBS FTC-TP level (adjusted hazard ratio 6.3; 95% confidence interval 3.8 to 10.2). The suboptimal long-term adherence based on low DBS TFV-DP levels was also associated with nonretention (adjusted hazard ratio 4.3; 95% confidence interval: 2.4 to 7.6).
Both short- and long-term metrics of PrEP adherence are strongly associated with future loss to follow-up in a U.S. demonstration project study. Short-term metrics of adherence, once available at the point-of-care, could be used to direct real-time tailored retention and adherence interventions.
aDivision of HIV, ID, and Global Medicine, University of California, San Francisco, CA;
bDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA;
cDepartment of Pharmaceutical Sciences, University of Colorado, Aurora, CO;
dSan Francisco Department of Public Health, San Francisco, CA;
eDepartment of Clinical Investigations, Whitman-Walker Health, Washington, DC; and
fDepartment of Medicine, University of Miami Miller School of Medicine, Miami, FA.
Correspondence to: Matthew A. Spinelli, MD, Division of HIV, ID, and Global Medicine, University of California, 995 Potrero Avenue, Ward 84, San Francisco, CA 94110 (e-mail: MatthewSpinelli@UCSF.edu).
Supported by National Insitute of Allergy and Infectious Diseases at the National Institute of Health [grant number 5T32AI060530 to M.A.S., R03AI120819 to D.G.; R01AI143340 and 2R01AI098472 to M.G.; U01AI106499 and U01AI084735 to P.L.A.; U01AI069451 to A.Y.L.]. D.G. and P.L.A. have received grants from Gilead Sciences, paid to their institutions. P.L.A., S.P.B., R.M.G. and A.Y.L. have led studies in which Gilead Sciences donated study drug.
The authors have no conflicts of interest to disclose.
Received December 07, 2018
Accepted February 04, 2019