Distribution of Cell-free and Cell-associated HIV surrogates in the Colon Following Simulated Receptive Anal Intercourse in Men who Have Sex with Men.

Published: September 20, 2011

Abstract
OBJECTIVES:

Describing the distribution and clearance of HIV surrogates within the gastrointestinal (GI) tract to inform rectal microbicide development.
DESIGN:

Radiolabeled, simulated HIV-infected semen was administered, imaged, and biopsied to simulate and measure colonic HIV distribution following 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 prior to simulated intercourse. These autologous leukocytes, radiolabeled with 9.25 MBq Indium-oxine (cell-associated HIV surrogate), and sulfur colloid particles, labeled with 37 MBq 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. Post-dosing, dual isotope SPECT/CT images were acquired at 1, 4, 8, and 24 hours. At 5 hours post-dosing, 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 recto-sigmoid colon in all subjects. SPECT showed at least 75% overlap in distribution of both surrogates up to 4 hrs following dosing. Biopsies indicate that 2.4% of CD4 cells extracted from recto-sigmoid colon tissue were exogenously administered.
CONCLUSIONS:

Our HIV surrogates stayed within the recto-sigmoid 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.

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