Men who have sex with men (MSM) are at high risk of HIV acquisition through unprotected receptive anal intercourse (URAI). This group accounts for the majority of the U.S. epidemic, as 69% of new HIV infections occur in MSM; however, URAI is also a significant HIV risk for trans- and cisgender women. Oral tenofovir (TFV)/emtricitabine (FTC), vaginal dapivirine ring, and injectable cabotegravir proved effective as HIV PrEP. However, vaginal rings do not protect from rectal HIV exposures, some persons at risk of HIV find adherence to oral PrEP challenging, some prefer avoidance of systemic drug exposure, and some prefer behaviorally-congruent PrEP options (adding antiretroviral drugs to products commonly used with sex, e.g., lubes and douches). We developed an on demand, behaviorally-congruent rectal TFV douche as a PrEP option for URAI. The TFV douche provided superior protection for rectal SHIV challenge in macaques vs. oral TFV/FTC and exceeded colon tissue active TFV concentration vs. the on demand Ipergay 2+1+1 TFV/FTC regimen in clinical studies.
Our goal was to compare colorectal distribution of an HIV surrogate & TFV douche when the TFV douche preceded or followed simulated receptive anal intercourse (sRAI). Five participants were enrolled for two study visits. At the first study visit, participants received an 111In-labeled TFV douche prior to sRAI using 99mTc-sulfur colloid in autologous semen as HIV surrogate. At the second study visit, the radiolabeled TFV douche was administered following radiolabeled sRAI. The primary outcome measure was the colorectal distribution of both douche and HIV radioisotopes using SPEC/CT.
The colorectal distribution of the TFV douche was equal to or greater than the HIV surrogate in all participants, regardless of the sequence, with one exception (J204 sRAI before douche), where the HIV surrogate had greater distribution toward the anus (Table). In all participants, the gastrointestinal distribution of the HIV surrogate increased when the douche was administered following sRAI.
Colorectal distribution of a TFV douche matched or exceeded the HIV surrogate in all participants, providing similar anatomic coverage as the HIV surrogate. The colorectal distribution of the HIV surrogate was greater when the TFV douche was administered following sRAI, therefore, douching following RAI may increase HIV distribution in the colon with uncertain, potentially increased, risk for HIV acquisition.