Abstract Body

Adherence to daily pre-exposure prophylaxis (PrEP) is difficult for many people so finding alternative strategies is a priority. HPTN 076 evaluated safety and acceptability of the long-acting injectable form of rilpivirine (TMC278 LA) for PrEP.

HPTN 076 is a phase 2, double-blind, 2:1 randomized trial comparing the safety of 1200mg TMC278 LA (LA) to placebo (P). Injectable product was administered to low risk, sexually active HIV-uninfected women in two gluteal, intramuscular (IM) injections every eight weeks over a 48-week period. Injections followed 28-days of self-administered daily oral rilpivirine (RPV, 25mg). Acceptability, safety and pharmacokinetic data were collected throughout the study. Product was paused for any participant with Grade (Gr) ≥2 related or Gr ≥3 unrelated adverse events (AEs).

A total of 136 (100 African, 36 US) women were enrolled; median age 31 years (IQR: 25,38), median weight 75kg (IQR: 64, 89), 46% married, 94% Black and 60% unemployed. Ten women withdrew (8 RPV, 2 P) and four had product discontinued (3 RPV, 1 P) during the oral phase (Weeks 0-4). A total of 122 (80 LA, 42 P) women received ≥ one injection; 98 (64 LA, 34 P) received all six injections. During the injection phase (Weeks 4-52), one woman withdrew (P) and 16 product discontinuations (10 LA, 6 P) occurred. Of the product discontinuations, 6 (8%) LA and 2 (5%) P were due to AEs including one P arm participant with prolonged QTc interval. Transient Gr ≥2 liver abnormalities occurred in 9 (11%) of the LA participants compared with 4 (10%) in the P arm. Three LA arm participants developed Gr ≥3 injection site reactions compared with none in the P arm. No significant difference was observed between the two arms. Among participants who received ≥ one injection, the median trough concentration (CTrough) of RPV was 68.2 ng/mL. At Week 52 (eight weeks after last injection), the CTrough was 91.9 ng/mL. The concentration two weeks (C2WK) after the first and second injections (at Weeks 6 and 14) was 85.5 ng/mL and 113 ng/mL, respectively. At the last injection visit, 61% of women strongly agreed that they would definitely use and 73% that they would think about using a PrEP injectable in the future.

TMC278 LA IM injections administered every eight weeks in this clinical trial cohort of African and US women were safe, overall well tolerated and acceptable. The lower quartile RPV concentrations were consistently above the PA-IC90 at all times through eight weeks post injection.