Distribution of cell-free and cell-associated HIV surrogates in the colon after simulated receptive anal intercourse in men who have sex with men.
Distribution of cell-free and cell-associated HIV surrogates in the colon after simulated receptive anal intercourse in men who have sex with men.
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DOI：
10.1097/qai.0b013e3182373b5e
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Hendrix CW
中科院分区：
文献类型：
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作者：
Louissaint NA;Nimmagadda S;Fuchs EJ;Bakshi RP;Cao YJ;Lee LA;Goldsmith J;Caffo BS;Du Y;King KE;Menendez FA;Torbenson MS;Hendrix CW
描述HIV替代物在胃肠道（GI）内的分布和清除，以告知直肠杀微生物剂的开发。放射性标记的，模拟HIV感染的精液管理，成像和活检，以模拟和测量结肠HIV分布后，肛交。本研究招募了有接受肛交史和使用肛交玩具经验的健康男性受试者。在模拟性交前收集单采分离的白细胞。将这些自体白细胞（用9.25 MBq 111铟-oxine（细胞相关HIV替代物）进行放射性标记）和硫胶体颗粒（用37 MBq 99 mTechnectium（无细胞HIV替代物）进行标记）与3 mL自体精浆混合。在5分钟的模拟性交后，通过带有尿道的人造阴茎将这种模拟HIV感染的精液给予受试者。给药后，在1、4、8和24小时采集双同位素SPECT/CT图像。在给药后5小时，收集结肠活检，提取CD 4细胞，并分析样品的放射性。SPECT/CT图像显示两种替代物的管腔分布相似，所有受试者的迁移仅限于直肠乙状结肠。SPECT显示给药后4小时内两种替代物的分布至少有75%重叠。活检表明，从直肠乙状结肠组织中提取的2.4%的CD 4细胞是外源性给予的。我们的HIV替代物在直肠乙状结肠内停留了24小时。外源性给药的自体淋巴细胞和HIV大小的颗粒迁移到相似的位置，并与管腔中的结肠组织结合。
Describing the distribution and clearance of HIV surrogates within the gastrointestinal (GI) tract to inform rectal microbicide development. Radiolabeled, simulated HIV-infected semen was administered, imaged, and biopsied to simulate and measure colonic HIV distribution following anal intercourse. 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 111Indium-oxine (cell-associated HIV surrogate), and sulfur colloid particles, labeled with 37 MBq 99mTechnectium (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. 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. 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.