Initiating Studies of Genitourinary HIV-1 Shedding among Kenyan Men

说明(申请人提供)：抗逆转录病毒疗法(ART)有可能大幅降低男性艾滋病毒-1的传染性，从而防止艾滋病毒-1感染的性传播，特别是在撒哈拉以南非洲。然而，男性生殖道HIV-1脱落的研究一直受到手淫收集精液样本困难的限制。这项建议的具体目的是：(1)评估在开始抗逆转录病毒治疗的男性中抑制生殖道和直肠粘膜艾滋病毒-1脱落的时间进程和程度；(2)评估前列腺后按摩液/尿液(后PMF/U)替代精液作为男性HIV-1传染性的替代标志物的有效性；(3)确定两种不同生殖器采样方法的可行性和可接受性：在HIV-1血清阳性的肯尼亚男性人群中，手淫和PMF/U后采集精液。我们将通过前瞻性地跟踪16名男性，在ART开始后的第一个月，确定生殖道和直肠粘膜样本中HIV-1的衰退动态。我们还将收集30名男性的配对生殖道样本，比较PMF/U后精浆中HIV-1RNA的水平。最后，我们将确定这两种不同的生殖道收集方法对于30名严格的异性恋者和30名双性恋者或同性恋者的可行性和可接受性。凭借华盛顿大学在男性HIV-1传染性方面的专业知识，在肯尼亚进行HIV-1脱皮研究的经验，以及能够接触到艾滋病毒-1传播高危男性的新队列，我们有信心开展拟议的研究。这项试点研究的结果将使我们能够计划进一步、更深入地研究男性传染性，以优化患者管理和公共卫生战略，以预防撒哈拉以南非洲的艾滋病毒-1性传播。艾滋病毒从男性传染给他们的性伴侣是艾滋病毒预防工作的主要关切，特别是在撒哈拉以南非洲。我们建议评估抗逆转录病毒治疗对艾滋病毒感染者生殖器和直肠分泌物中检测到的艾滋病毒数量的影响。由于生殖器样本很难从男性身上采集，我们将评估两种不同的采集方法在肯尼亚异性恋男性和男男性行为者中的有效性、可行性和可接受性。

DESCRIPTION (provided by applicant): Antiretroviral therapy (ART) has the potential to substantially reduce male HIV-1 infectivity and thereby prevent sexual transmission of HIV-1 infection, especially in sub-Saharan Africa. However, studies of male genitourinary HIV-1 shedding have been limited by difficulties with collecting semen samples by masturbation. The specific aims of this proposal are to: (1) evaluate the time course and magnitude of suppression of genitourinary and rectal mucosal HIV-1 shedding among men initiating ART; (2) to evaluate the validity of post-prostatic massage fluid/urine (post-PMF/U) as a surrogate marker of male HIV-1 infectivity in place of semen; and (3) to determine the feasibility and acceptability of two different genital sampling methods: semen collection by masturbation versus post-PMF/U in a population of HIV-1- seropositive Kenyan men. We will determine the dynamics of HIV-1 decay in genitourinary and rectal mucosal samples by prospectively following 16 men over the first month after ART initiation. We will also collect paired genitourinary specimens from 30 men to compare HIV-1 RNA levels in seminal plasma versus post-PMF/U. Finally, we will determine the feasibility and acceptability of these two different genitourinary collection methods for 30 strictly heterosexual and 30 bisexual or homosexual men. With the University of Washington's expertise in male HIV-1 infectivity, experience in conducting HIV-1 shedding studies in Kenya, and a new cohort with access to men at high risk for HIV-1 transmission, we are confident of our ability to carry out the proposed research. The results of this pilot study will enable us to plan further, more in-depth research on male infectivity to optimize patient management and public health strategies for the prevention of sexual HIV-1 transmission in sub-Saharan Africa. Transmission of HIV from men to their sexual partners is of major concern for HIV prevention efforts, especially in sub-Saharan Africa. We propose to evaluate the impact of antiretroviral therapy on the amount of HIV detected in the genital and rectal secretions of HIV-infected men. Because genital samples are difficult to collect from men, we will evaluate the validity, feasibility, and acceptability two different collection methods in heterosexual men and men who have sex with men in Kenya.