Brief Report: Mapping Colorectal Distribution of Cell-Free and Cell-Associated HIV Surrogates Following Simulated Anal Intercourse to Aid Rectal Microbicide Development

Background:Anal sex remains the greatest HIV transmission risk for men who have sex with men and carries substantial population attributable risk among women. Despite a growing array of HIV preexposure prophylaxis (PrEP) options, rectal microbicides remain desirable as on-demand, nonsystemic PrEP. Rectal microbicide product development for PrEP requires understanding the spatiotemporal distribution of HIV infectious elements in the rectosigmoid to optimize formulation development.Setting:Outpatient setting with healthy research participants.Methods:Six healthy men underwent simulated receptive anal sex with an artificial phallus fitted with a triple-lumen catheter in the urethral position. To simulate ejaculation of HIV-infected semen, autologous seminal plasma laden with autologous blood lymphocytes from apheresis labeled with ¹¹¹Indium-oxine (cell-associated) and ^99mTechnetium-sulfur colloid (cell-free) as HIV surrogates was injected into the rectal lumen through the phallic urethra. Spatiotemporal distribution of each radioisotope was assessed using single-photon emission computed tomography/CT over 8 hours. Analysis of radiolabel distribution used a flexible principal curve algorithm to quantitatively estimate rectal lumen distribution.Results:Cell-free and cell-associated HIV surrogates distributed to a maximal distance of 15 and 16 cm, respectively, from the anorectal junction (∼19 and ∼20 cm from the anal verge), with a maximal signal intensity located at 6 and 7 cm, respectively. There were no significant differences in any distribution parameters between cell-free and cell-associated HIV surrogates.Conclusions:Cell-free and cell-associated HIV surrogate distribution in the rectosigmoid can be quantified with spatiotemporal pharmacokinetic methods. These results describe the ideal luminal target distribution to guide rectal microbicide development.