Comparing applicator vs. 'as lubricant' delivery of rectal dapivirine gel (MTN-033)

Background: Rectal microbicides are promising strategies for local, non-systemic delivery of HIV pre-exposure prophylaxis, especially in men who have sex with men. Tenofovir gel administered intrarectally with an applicator had lower acceptability as compared to a daily oral PrEP regimen and traditional lubricant use in prior phase II studies. Data to enhance the behaviorally congruent delivery of rectal microbicides as lubricants are scant. Methods: MTN-033, a single site, open label, sequence randomized, crossover study, enrolled HIV negative men to receive 0.05% dapivirine (DPV) gel by intrarectal dosing using an applicator (2.5 g) and self-administered on an artificial phallus as lubricant (up to 10 g). Plasma, rectal fluid, and rectal biopsies were collected over 24 hr post dose. Participants completed behavioral acceptability surveys after each dosing regimen. We compared delivery methods using Wilcoxon tests for PK parameters. Results: 16 participants used DPV gel by applicator and 15/16 participants used gel as lubricant (mean 1.8 g, SD 0.8). No related adverse events were reported. Participants all felt the gel was easy to use. Peak DPV concentration in plasma (pg/mL) was higher using an applicator, median 319 (interquartile range [IQR] 247, 603), than use as lubricant, 85 (IQR 54, 218; p < 0.01). Plasma DPV 24 hour area under the curve (ng-hr/mL) after applicator (median 3.5; IQR 3.1, 6.2) was higher than after use as lubricant (median 1.3, IQR 0.7 to 2.4; p < 0.01) Mean DPV concentrations in rectal fluid 1 hr post dose were similar with applicator and as lubricant, 20.9 (SD 33.6) and 25.6 (SD 23.8) pg/mg respectively. DPV was detected in only 1/31 rectal biopsies collected at 1 and 4 hr post dose. Conclusions: Evidence of local delivery and systemic absorption of DPV when dosed as an anal lubricant indicates potentially feasible development of lubricant delivered rectal microbicides. However, roughly 3-fold lower DPV exposure in plasma and lack of detectable DPV in tissue biopsies indicate formulation changes are necessary to achieve protective tissue concentrations informed by vaginal microbicide experience. Our data suggests that DPV gel was safe and easy to use. Further development of a lubricant microbicide strategy is warranted.
OA16.03 K. Ho (1); C. Dominguez-Islas (2); D. Szydlo (3); N. Macagna (4); R. Brand (1); J. Piper (5); J. Bauermeister (6); M. Marzinke (7); S. Riddler (1); S. Edick [...]