An HIV Prevention Program for Mochudi, Botswana

描述(由申请人提供)： 博茨瓦纳莫丘迪的艾滋病毒预防计划摘要根据联合国艾滋病规划署的数据，博茨瓦纳的艾滋病毒流行率位居世界第二。在非洲，博茨瓦纳实现了自愿艾滋病毒检测和提供免费抗逆转录病毒疗法和围产期艾滋病毒传播预防干预措施的最高比率。然而，尽管正在进行预防和治疗努力，艾滋病毒流行率/发病率并没有显著变化，而且当地对实施更有效的预防干预措施有相当大的兴趣。我们向博茨瓦纳南部村庄Mochudi的15-49岁年轻人提出了一整套行为和生物医学干预措施，包括(1)常规、选择退出艾滋病毒检测；(2)教育，鼓励改变行为，包括使用避孕套；(3)男性包皮环切术；(4)针对艾滋病毒感染者的急性感染和/或高病毒载量(VL)的三种药物HAART。我们将在实施干预措施前后对莫丘迪的所有人口进行反复筛查，以确定艾滋病毒的流行和发病率。对艾滋病毒检测、避孕套使用和其他行为建议的接受程度将通过对整个村庄的反复调查进行评估。将在莫丘迪东北部地区(人口14,000)评估对其他干预措施的接受情况以及利用聚合酶链式反应和接触者追踪调查的事件感染源。将进行病毒基因分型，通过对感染个体的序列分析来识别潜在的病毒网络或簇。将开发数学模型并将其参数化，以反映莫丘迪的疫情，并根据监测活动提供的信息进行更新。这些模型将被用来确定预防措施之间的潜在协同作用，并估计必须达到什么复盖/吸收和有效性的综合水平才能将社区内病毒的有效繁殖数量保持在1以下。具体目标是(1)通过估计21年半期间3个时间点的艾滋病毒和行为危险因素的发病率和流行率来描述Mochudi的艾滋病毒流行特征；(2)确定自愿咨询和检测的接受率、避孕套的使用、通过接触者追踪和男性割礼来接受伴侣通知；(3)通过基因组签名追踪来确定传播与传播之间的关联，以评估传播与高VL之间的关联；(4)估计根据国家指南(艾滋病定义的疾病或CD4&lt；250)不符合治疗条件的急性感染和/或VL e 100,000艾滋病毒感染者在发现后接受HAART的比率，并评估遵守药物时间表以及基线和新耐药性的比率；以及(5)制定基于模型的预测和流行病控制潜力的评估，并使用这些模型来评估预防措施组合的成本效益。博茨瓦纳莫丘迪艾滋病毒预防计划申请的目的是证明一项全面的干预计划的可行性和可接受性，以减少莫丘迪的艾滋病毒发病率，莫丘迪是博茨瓦纳南部的一个村庄，有39,000人，成年人中艾滋病毒感染率为25%。这一综合干预措施将包括行为矫正教育、成年男性包皮环切术和使用抗逆转录病毒药物以减少社区一级的传播。最终目标是评估可在博茨瓦纳和南部非洲扩大为公共卫生政策的预防干预措施。

DESCRIPTION (provided by applicant): An HIV Prevention Program for Mochudi, Botswana Summary According to UNAIDS, Botswana has the second-highest prevalence of HIV in the world. Within Africa, Botswana has achieved the highest rates of voluntary HIV testing and of provision of free HAART and perinatal HIV transmission prevention interventions. Nevertheless, HIV prevalence/incidence have not changed significantly despite ongoing prevention and treatment efforts, and considerable local interest exists in implementation of more effective prevention interventions. We propose a comprehensive package of behavioral and biomedical interventions to 15-49-year-olds in Mochudi, a village in the south of Botswana, including (1) routine, opt-out HIV testing; (2) education to encourage behavior modification, including condom use; (3) male circumcision; and (4) three-drug HAART for HIV-infected persons with acute infections and/or high viral loads (VL). We will determine HIV prevalence and incidence using repeated screening of the entire population in Mochudi before and after implementation of interventions. Uptake of HIV testing, condom use, and other behavioral recommendations will be assessed from repeated surveys of the entire village. Uptake of the other interventions, and the sources of incident infections investigated using PCR and contact tracing, would be evaluated in the northeast section of Mochudi (population, 14,000). Viral genotyping will be performed to identify potential viral networks or clusters by sequence analysis of infected individuals. Mathematical models will be developed and parameterized to reflect the epidemic in Mochudi and updated by information from surveillance activities. These models will be used to identify potential synergies among preventive measures and to estimate what combined levels of coverage/uptake and effectiveness must be achieved to hold the effective reproductive number of the virus in the community below one. The Specific Aims are (1) to characterize the HIV epidemic in Mochudi by estimating incidence and prevalence of HIV and of behavioral risk factors at 3 time points over a 21/2-year period; (2) to determine uptakes of voluntary counseling and testing, condom use, acceptability of partner notification with contact tracing, and male circumcision; (3) to identify transmission associations with genome signature tracing to evaluate associations between transmissions and high VL; (4) to estimate the rate of acceptance of HAART offered upon detection to HIV-infected individuals with acute infection and/or VL e 100,000 who do not otherwise qualify for treatment based on national guidelines (AIDS-defining illness or CD4 < 250), and to assess adherence to drug schedules and rates of baseline and new drug resistance; and (5) to develop model-based projections and assessments of the potential for epidemic control, and to use these models to evaluate the cost effectiveness of combinations of preventive interventions. An HIV Prevention Program for Mochudi, Botswana Relevance The goal of the application is to demonstrate the feasibility and acceptability of a comprehensive program of interventions to reduce HIV incidence in Mochudi, a village of 39,000 people in southern Botswana with an HIV prevalence of 25% in adults. This combination of interventions will include education for behavior modification, circumcision of adult males, and the use of antiretroviral drugs to decrease transmission at the community level. The ultimate goal is to evaluate prevention interventions that could be scaled up as public health policy in Botswana and southern Africa.