BOSTON — Although pre-exposure prophylaxis use has been shown to weaken bone mineral density, late-breaking data from a substudy of the iPrEx trial presented at CROI 2016 suggested that stopping the preventive treatment may lead to full hip and spine recovery.
“PrEP containing [tenofovir disoproxil fumarate (TDF)] has been associated with a 0.5% to 1.5% decrease in [bone mineral density (BMD)] depending on the amount of adherence and drug exposure,” Robert M. Grant, MD, MPH, of the Gladstone Institutes in San Francisco, said during a presentation. “Recovery of BMD after stopping PrEP has not been fully evaluated.”
Robert M. Grant
To do so, Grant and colleagues conducted a substudy of the iPrEx trial and iPrEx open-label extension, which studied the efficacy of Truvada (emtricitabine [FTC]/TDF, Gilead Sciences) as PrEP for men who have sex with men and transgender women who have sex with men. The substudy examined BMD among participants consecutively enrolled in both trials using X-ray absorptiometry (DXA) every 24 weeks during PrEP use, 24 weeks after halting PrEP and at the initiation of the open-label extension. As a tenofovir-diphosphate (TFV-DP) concentration of 16 fmol/million cells was associated with 90% HIV protection, the BMD of participants who recorded this TFV-DP level at 24 weeks were compared with those who either did not achieve the protective concentration or were randomly assigned a placebo.
iPrEx enrollees (n = 498) from five international cities were included in the substudy’s analysis (median age, 25 years). Of these, 11% identified as transsexual, 43% were smokers and 81% reported alcohol use. More than 70% received DXA scans 24 weeks after stopping PrEP, and 58% were scanned upon their initiation into the open-label extension.
After a decline in BMD during treatment, DXA after stopping PrEP revealed an average annual spinal recovery rate of 1.81% (P = .01) and an average annual hip recovery rate of 1.13% (P = .002) among participants with protective drug concentrations at 24 weeks. This group also demonstrated complete spinal recovery by 6 months, and complete hip and spine recovery at the initiation of the open-label extension (median, 73 weeks). This recovery persisted after adjusting for age and drug concentrations, although younger participants demonstrated swifter hip recovery than older participants.
“BMD appears to be a dynamic process, which does return to placebo levels after stopping PrEP,” Grant said. “The guidance regarding when to start and stop PrEP are important for maximizing PrEP benefits and minimizing its side effects, including its effect on BMD.” – by Dave Muoio
Grant RM, et al. Abstract 48LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.
Disclosure: Grant reports Gilead Science’s provision of the study drug for the iPrEx trial, as well as contracts between his employer (the Gladstone Institutes), Gilead Science and ViiV Healthcare for research on long-acting injectable PrEP.