title: Distribution of cell-free and cell-associated HIV surrogates in the colon after simulated receptive anal intercourse in men who have sex with men.
abstract: OBJECTIVE
  Describing the distribution and clearance of HIV surrogates within the gastrointestinal tract to inform rectal microbicide development.
  
  
  METHODS
  Radiolabeled simulated HIV-infected semen was administered, imaged, and biopsied to simulate and measure colonic HIV distribution after anal intercourse.
  
  
  METHODS
  Healthy male subjects with a history of receptive anal intercourse and experience with the use of anal sex toys were recruited to this study. Apheresis isolated leukocytes were collected before simulated intercourse. These autologous leukocytes, radiolabeled with 9.25 MBq (111)Indium-oxine (cell-associated HIV surrogate), and sulfur colloid particles, labeled with 37 MBq (99m)Technectium (cell-free HIV surrogate), were mixed in 3 mL autologous seminal plasma. This simulated HIV-infected semen was administered to subjects via an artificial phallus with urethra after 5 minutes of simulated intercourse. Postdosing dual isotope Single photon emission computed tomography coupled with traditional computed tomography (SPECT/CT) images were acquired at 1, 4, 8, and 24 hours. At 5 hours postdosing, colon biopsies were collected, CD4 cells were extracted, and samples analyzed for radioactivity.
  
  
  RESULTS
  SPECT/CT images showed similar luminal distribution for both surrogates, with migration limited to the rectosigmoid colon in all subjects. SPECT showed at least 75% overlap in distribution of both surrogates up to 4 hours after dosing. Biopsies indicate that 2.4% of CD4 cells extracted from rectosigmoid colon tissue were exogenously administered.
  
  
  CONCLUSIONS
  Our HIV surrogates stayed within the rectosigmoid colon for 24 hours. Exogenously dosed autologous lymphocytes and HIV-sized particles migrate to similar locations and associate with the colonic tissue in the lumen.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Nicolette A
authors.initials: NA
authors.lastname: Louissaint
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Bakshi
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Cao
authors.forename: Linda A
authors.initials: LA
authors.lastname: Lee
authors.forename: Jeff
authors.initials: J
authors.lastname: Goldsmith
authors.forename: Brian S
authors.initials: BS
authors.lastname: Caffo
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Karen E
authors.initials: KE
authors.lastname: King
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Menendez
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.forename: Craig W
authors.initials: CW
authors.lastname: Hendrix
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage; D003106:Colon / Q000502:physiology*; D015658:HIV Infections / Q000209:etiology; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D012661:Semen / Q000166:cytology / Q000821:virology; D012725:Sexual Behavior / Q000502:physiology*; D013671:Technetium Tc 99m Sulfur Colloid; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D000890:Anti-Infective Agents; D011849:Radioactive Tracers; D013671:Technetium Tc 99m Sulfur Colloid