Antiretroviral Therapy and HIV-1 Infectivity in Women

描述(申请人提供)：最近的事件降低了撒哈拉以南非洲抗逆转录病毒治疗的成本障碍，那里有数百万人可以从这种治疗中受益。除了延长生命外，抗逆转录病毒药物还可以提供一个强大的工具来减少病毒的传播。然而，促进病毒复制或增加性行为风险的辅助因素可能会削弱抗逆转录病毒药物对艾滋病毒-1传播的好处。拟议研究的目的是确定这些因素之间的复杂相互作用，以便了解抗逆转录病毒药物的引入将如何影响艾滋病毒-1的性传播。我们提出了一系列研究，利用生殖器HIV-1作为肯尼亚蒙巴萨核心传播者妇女群体中传染性的标志。这项研究将解决以下关键假设。首先，抗逆转录病毒治疗将使生殖器艾滋病毒-1水平迅速和持续下降。第二，即使在使用抗逆转录病毒药物的情况下，也有一些可改变的因素会增加生殖器中艾滋病毒-1的脱落。这些COF参与者代表了有吸引力的目标，以增加抗逆转录病毒治疗的好处，以降低艾滋病毒-1的传染性。最后，我们假设，抗逆转录病毒药物的引入可能会对性风险产生不利影响，这可能会抵消减少HIV-1脱落率的好处。这一假设将通过测量引入抗逆转录病毒药物前后传染性生殖道感染发病率的变化来进行评估。将从现有队列中招募100名HIV-1血清阳性妇女。开始长期抗逆转录病毒治疗的女性将接受一系列检查，以确定抗逆转录病毒药物、CD4计数、血浆病毒载量、坚持治疗、生殖道感染和荷尔蒙避孕药对艾滋病毒-1脱落的影响。这些研究将有助于指导制定干预措施，以应对艾滋病毒-1在服用抗逆转录病毒药物的妇女中的传染性、荷尔蒙、免疫学、病毒学和药理学影响因素，并将查明随着获得抗逆转录病毒治疗的机会增加，可能发生的性风险的变化。

DESCRIPTION (provided by applicant): Recent events have lowered the cost barrier to antiretroviral therapy in sub-Saharan Africa, where millions of people could benefit from such treatment. In addition to prolonging lives, antiretrovirals could provide a powerful tool for decreasing the spread of the virus. However, cofactors that enhance viral replication or an increase in sexual risk taking could mitigate the benefits of antiretrovirals on HIV-1 transmission. The objective of the proposed research is to define the complex interplay of these factors in order to understand how the introduction of antiretrovirals will influence sexual transmission of HIV-1. We propose a series of studies utilizing genital HIV-1 as a marker for infectiousness in a core transmitter group of women in Mombasa, Kenya. This research will address the following key hypotheses. First, that antiretroviral therapy will produce a rapid and sustained reduction in genital HIV-1 levels. Second, that there are modifiable cof actors that increase genital HIV-1 shedding even in the face of antiretrovirals. These cof actors represent attractive targets to augment the benefits of antiretroviral therapy for reducing HIV-1 infectivity. Finally, we hypothesize that the introduction of antiretrovirals may adversely influence sexual risk, which could offset the benefit of decreased HIV-1 shedding. This hypothesis will be evaluated by measuring changes in the incidence of communicable genital tract infections before and after the introduction of antiretrovirals. One hundred HIV-1 seropositive women will be recruited from an existing cohort. Women initiating long-term antiretroviral therapy will have serial examinations to determine the effects of antiretrovirals, CD4 count, plasma viral load, adherence to therapy, genital tract infections, and hormonal contraceptives on HIV-1 shedding. These studies will help to guide the development of interventions to address infectious, hormonal, immunologic, virologic, and pharmacologic cof actors for HIV-1 infectivity among women on antiretrovirals, and will identify changes in sexual risk that may occur as access to antiretroviral therapy increases.