Initiating Studies of Genitourinary HIV-1 Shedding among Kenyan Men

描述（由申请人提供）：抗逆转录病毒疗法（ART）有可能大幅降低男性HIV-1感染率，从而预防HIV-1感染的性传播，特别是在撒哈拉以南非洲地区。然而，男性泌尿生殖道HIV-1脱落的研究受到通过手淫收集精液样本的困难的限制。该提案的具体目的是：（1）评价开始ART的男性中生殖泌尿和直肠粘膜HIV-1脱落受到抑制的时间过程和程度;（2）评价前列腺按摩后液体/尿液的有效性（PMF/U后）作为男性HIV-1感染性的替代标志物，代替精液;以及（3）确定两种不同生殖器取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，通过手淫与PMF/U后收集精液。我们将通过前瞻性随访16名男性在ART开始后的第一个月，确定生殖泌尿道和直肠粘膜样本中HIV-1衰减的动态。我们还将从30名男性中收集配对的泌尿生殖道标本，以比较精浆与PMF/U后的HIV-1 RNA水平。最后，我们将确定这两种不同的泌尿生殖道收集方法的可行性和可接受性为30个严格的异性恋和30个双性恋或同性恋男性。凭借华盛顿大学在男性HIV-1感染性方面的专业知识，在肯尼亚进行HIV-1脱落研究的经验，以及接触HIV-1传播高危男性的新队列，我们有信心有能力开展拟议的研究。这项试点研究的结果将使我们能够计划对男性传染性进行进一步、更深入的研究，以优化患者管理和公共卫生战略，预防撒哈拉以南非洲的艾滋病毒1型性传播。男子将艾滋病毒传染给其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HIV感染男性生殖器和直肠分泌物中检测到的HIV数量的影响。由于生殖器样本很难从男性中收集，我们将在肯尼亚异性恋男性和男男性行为者中评估两种不同收集方法的有效性、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.