Reaching Unaware Sexual and Social Contacts to Interrupt Ongoing HIV Transmission

描述(由申请人提供)：不知道自己感染艾滋病毒的人对正在进行的艾滋病毒传播的贡献不成比例。治疗即预防(TasP)取决于向艾滋病毒感染者提供艾滋病毒检测和诊断，将他们与护理联系起来，并启动抗逆转录病毒治疗。如果很大一部分正在进行的传播与急性或最近的艾滋病毒感染有关，则TASP的有效性可能会降低，但急性艾滋病毒感染(AHI)给诊断带来了挑战。识别患有AHI和最近感染的人可能对充分发挥TasP的潜力至关重要。在撒哈拉以南非洲，伙伴通知是一项未得到充分利用的战略，用来确定未确诊的艾滋病毒感染者。合同性伙伴通知是一种具有成本效益的伙伴通知形式，给新诊断的艾滋病毒感染者有限的时间通知他们的性伙伴，然后由保健人员积极追踪。社会接触转介包括转介同龄人进行艾滋病毒检测。这种做法的理由是，艾滋病毒感染者的社会接触者可能会有类似的高危行为，从而增加他们感染艾滋病毒的可能性。我们的核心假设是：1)新发现的艾滋病毒感染者性传播感染诊所的伴侣通知和社会接触转介将有效地识别艾滋病毒感染者，但不知情的人是持续传播的高风险者；2)艾滋病毒感染者的不知情性伴侣和最近感染艾滋病毒的人的社会接触者，基于性行为、病毒载量和集群成员资格，将比不知情的性伴侣和慢性艾滋病毒感染者的社会接触者更有可能传播艾滋病毒。我们将在马拉维的利隆圭探讨这些假设，具体目的有三：目标1：评估“不知情干预方案”，包括检测AHI、合同伙伴通知和社会接触转介，以发现不知道其艾滋病毒感染情况的人；目标2：通过评估性行为、对艾滋病毒状况的认识、病毒载量和在急性、近期和长期感染艾滋病毒的性传播门诊顾客及其性伙伴和社会接触者之间的系统进化聚集性，表征持续传播艾滋病毒的可能性；目标3：使用数学模型评估AHI检测、合同伙伴通知和社会接触转介以减少艾滋病毒发病率的可能性。为了实现这些目标，我们将在马拉维的两个性传播感染诊所招募艾滋病毒感染者。我们将评估结合AHI检测、合同合作伙伴通知和社会联系推荐的不知情干预方案。我们将使用HIV血清学、HIV RNA聚合酶链式反应、多检测算法和探索性深度测序方法，对INDE参与者、性伴侣和社会接触者的HIV感染进行分期。将对所有已确定的感染进行系统发育链接和聚类分析。将使用数学模型来评估这些干预措施在人口层面的潜在影响。

DESCRIPTION (provided by applicant): Persons unaware of their HIV infection contribute disproportionately to ongoing HIV transmission. Treatment as prevention (TasP) depends on reaching HIV-infected persons for HIV testing and diagnosis, linking them to care, and initiating antiretroviral therapy. TasP effectiveness may be reduced if a significant proportion of ongoing transmission is related to acute or recent HIV infection, but acute HIV infection (AHI) presents diagnostic challenges. Identifying persons with AHI and recent infection may be critical for the realization of the full potential of TasP. Partner notification is an underused strategy in sub-Saharan Africa to identify persons with undiagnosed HIV infection. Contract partner notification is a cost-efficient form of partner notification, in which newly diagnosed HIV-infected persons are given a limited time to notify their sexual partners, followed by active tracing by health personnel. Social contact referral involves referral of peers for HIV testing. The rationale for ths approach is that social contacts of HIV-infected persons are likely to share similar high-risk behaviors, thereby increasing their likelihood of HIV infection. Our central hypotheses are: 1) Partner notification and social contact referral of newly identified HIV- infected STI clinic patros will effectively identify HIV-infected-but-unaware persons at high risk for ongoing transmission, and 2) HIV-infected unaware sexual partners and social contacts of persons with acute and recent HIV infection will have greater potential for HIV transmission, based on sexual behavior, viral load, and cluster membership, than unaware sexual partners and social contacts of chronically HIV-infected persons. We will address these hypotheses in Lilongwe, Malawi with three specific aims: Aim 1: To evaluate an "unaware intervention package", including detection of AHI, contract partner notification, and social contact referral, to find persons unaware of thei HIV infection; Aim 2: To characterize the potential for ongoing HIV transmission through evaluation of sexual behaviors, awareness of HIV status, viral load, and phylogenetic clustering among acute, recent, and chronically HIV-infected STI clinic patrons and their sexual partners and social contacts; Aim 3: To assess the potential for AHI detection, contract partner notification, and social contact referral to reduce HIV incidence using mathematical modeling. To address these aims, we will recruit HIV-infected persons in two sexually transmitted infection clinics in Malawi. We will assess an unaware intervention package combining AHI detection, contract partner notification, and social contact referral. We will stage the HIV infection of inde participants, sexual partners and social contacts using HIV serology, HIV RNA PCR, a multi-assay algorithm, and an exploratory deep sequencing approach. Phylogenetic linkage and cluster analyses will be performed for all identified infections. Mathematical modeling will be used to assess the potential population-level impact of these interventions.