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）具有显著降低男性HIV-1感染的潜力，从而防止HIV-1感染的性传播，特别是在撒哈拉以南非洲。然而，男性泌尿生殖系统HIV-1脱落的研究一直受到通过手淫收集精液样本的困难的限制。本提案的具体目的是：(1)评估在接受抗逆转录病毒治疗的男性中抑制泌尿生殖系统和直肠粘膜HIV-1脱落的时间过程和程度；(2)评价前列腺后按摩液/尿（post-PMF/U）代替精液作为男性HIV-1感染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，手淫采集精液与pmf /U后采集精液。我们将通过对16名男性进行ART治疗后第一个月的前瞻性随访，来确定HIV-1在泌尿生殖系统和直肠粘膜样本中的衰变动态。我们还将收集来自30名男性的配对泌尿生殖系统标本，以比较精浆中HIV-1 RNA水平与pmf /U后的水平。最后，我们将对30名严格的异性恋和30名双性恋或同性恋男性确定这两种不同的泌尿生殖系统采集方法的可行性和可接受性。由于华盛顿大学在男性艾滋病毒-1感染方面的专业知识，在肯尼亚开展艾滋病毒-1脱落研究的经验，以及有机会接触艾滋病毒-1传播高风险男性的新队列，我们对开展拟议研究的能力充满信心。这项试点研究的结果将使我们能够规划进一步、更深入的男性传染性研究，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。男性向性伴侣传播艾滋病毒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。由于很难从男性身上收集生殖器样本，我们将评估两种不同收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.