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Primary Objective 

  • To characterize the systemic and compartmental pharmacokinetics of dapivirine 0.05% gel applied rectally by two different methods

Study Summary
Intermittent dosing of a rectal microbicide gel associated with sexual activity may be a more feasible strategy for long-term usage. Data are needed on the pharmacokinetics, safety, and acceptability of applying dapivirine gel as a lubricant in at-risk men who have sex with men (MSM) and transgender females who have sex with men.

MTN-033 was a Phase 1, randomized, open label, single-site trial designed to evaluate the pharmacokinetics of dapivirine gel (0.05%) when administered rectally via HTI vaginal applicator and a coital simulation device to healthy, HIV-1 uninfected men and transgender women. The study enrolled 16 participants ages 18 and older. Participants administered a single dose of dapivirine gel (DPV 0.05%) in each study sequence. Participants were randomized to one of two product application sequences.  Product sequences included the application of a single dose of study product via applicator (2.5 g) and administration of up to 10 g of dapivirine gel applied via a coital simulation device (to simulate receptive anal intercourse); order of administration was randomly selected. A washout period occurred between each product application visit. This design allowed for the collection of valuable pharmacokinetic (PK) data from those exposed to a single dose of dapivirine gel rectally (which may be representative of episodic or coital dosing) with and without the use of a coital simulation device. The ideal coital-dosing regimens for dapivirine gel applied rectally are not yet known.

MTN-033 completed follow-up on December 5, 2018. Primary results were presented at the HIV Research for Prevention (HIVR4P) conference held virtually on January 27-28 and February 3-4 in 2021. One paper has been published from this study. Primary and secondary manuscripts are in development. 

Primary Results
Sixteen 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 0.7-2.4; p<0.01) Mean DPV concentrations in rectal fluid 1 hour 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-hour post dose.

Protocol Chair(s)
Ho, Ken (Protocol Chair)
Protocol Title
An Open Label Randomized Phase 1 Pharmacokinetic Study of Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults
DAIDS Protocol ID
Study Focus/Product Administration
Study Type
Study Phase
Phase I  
United States
Men (cisgender men, non‐transgender men)   
Transgender women
Division of AIDS, US National Institute of Allergy and Infectious Diseases
US Eunice Kennedy Shriver National Institute of Child Health and Human Development
US National Institute of Mental Health
US National Institutes of Health
Other Study Info

Phase I, randomized, open label trial