Rectally applied antiretroviral
microbicides for preexposure prophylaxis (PrEP) of
HIV infection are currently in development. Since
enemas (rectal douches) are commonly used by men who have sex with men prior to receptive anal intercourse, a
microbicide enema could enhance PrEP adherence by fitting seamlessly within the usual sexual practices. We assessed the distribution, safety, and acceptability of three
enema types-hyperosmolar (Fleet), hypoosmolar (distilled water), and isoosmolar (
Normosol-R)-in a crossover design. Nine men received each
enema type in random order.
Enemas were radiolabeled [(99m)Tc-
diethylene triamine pentaacetic
acid (
DTPA)] to assess
enema distribution in the colon using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Plasma (99m)Tc-DTPA indicated mucosal permeability. Sigmoidoscopic colon tissue biopsies were taken to assess injury as well as tissue penetration of the (99m)Tc-DTPA. Acceptability was assessed after each product use and at the end of the study. SPECT/CT imaging showed that the isoosmolar
enema had greater proximal colonic distribution (up to the splenic flexure) and greater
luminal and colon tissue concentrations of (99m)Tc-DTPA when compared to the other
enemas (p<0.01). Colon biopsies also showed that only the hyperosmolar
enema caused sloughing of the colonic epithelium (p<0.05). In permeability testing, the hypoosmolar
enema had higher plasma (99m)Tc-DTPA 24-h area under the concentration-time curve and peak concentration compared to the hyperosmolar and isoosmolar
enemas, respectively. Acceptability was generally good with no clear preferences among the three
enema types. The isoosmolar
enema was superior or similar to the other
enemas in all categories and is a good candidate for further development as a rectal
microbicide vehicle.