Abstract Body

Background: CDC recommends 3-drug post-exposure prophylaxis (PEP) with emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) plus raltegravir (RAL) for 28 days. But in one non-occupational (N)PEP study, FTC-TDF-RAL adherence was imperfect (only 52% took all 3 pills/day) and RAL was associated with acute muscle adverse effects (9%). FTC-TDF coformulated with rilpivirine (RPV) as a single-tablet regimen (STR) is a well-tolerated, once-daily NPEP candidate. A plasma tenofovir (TFV) level >40ng/mL is thought to reflect recent full adherence, whereas a level <10ng/mL suggests no dose for ≥7 days. NPEP studies to date have neither evaluated STRs nor measured TFV levels. We hypothesized FTC/RPV/TDF as an STR NPEP would be safe, well-tolerated, and result in high adherence. Methods: We evaluated NPEP with STR FTC/RPV/TDF for 28 days in gay men after high-risk, sexual exposure, in an open-label, single-arm study. We assessed adherence (pill count; patient report; and plasma TFV levels at Week 4 in a subset by HPLC), adverse events (AEs) and HIV status through Week 12. Final intention-to-treat (ITT) analyses are reported. Results: 100 men (mean age 31 years [SD 9]) presented a mean 30 hours (SD 21) after anal sex (88% receptive). NPEP commenced 2 hours (SD 2.3) post-presentation. No participant was HIV+ at enrolment or through Week 12, or ceased NPEP because their ‘source’ was found to be HIV-negative. NPEP completion was 92% (95%CI 85 to 96); failures occurred at median 14 days for loss to follow-up (6%), adverse event (1%) or study burden (1%). NPEP adherence was 98.6% (SD 2.7) by self-report. In the 78 participants with pill-count data, adherence was 98.7% (SD 2.4). 86% reported taking all doses with food. Of 78 paired assessments available for percent adherence by pill count and self-report, agreement was 100% (kappa=1.0; P<0.0001). From the final 50 participants, plasma TFV was measured within 48 hours of the last dose in 41 (88%) participants who reached Day 28 (mean 16 hrs [SD 10]): 36 (88%) participants had levels >40ng/mL and only 1 (2%) was <10ng/mL. One participant developed pancreatitis 1 day post-NPEP. 5 other participants developed a Grade 3 AE; 2 possibly due to study drug. Grade 3+ lab AEs possibly due to study drug occurred in 2 participants. Mean serum creatinine rose from 83 to 88 µM/L at Day 28 (P<0.001), but with no grade 1+ increase and no significant change in serum phosphate. Conclusions: STR FTC/RPV/TDF was well-tolerated as once-daily NPEP, with high levels of adherence and completion.