An HIV Prevention Program for Mochudi, Botswana

描述（由申请人提供）： 根据联合国艾滋病规划署的数据，博茨瓦纳是世界上艾滋病毒感染率第二高的国家。在非洲，博茨瓦纳的自愿艾滋病毒检测率和免费提供高效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比率最高。然而，尽管不断作出预防和治疗努力，艾滋病毒的流行率/发病率没有显著变化，地方上对实施更有效的预防干预措施有很大兴趣。我们建议对博茨瓦纳南部村庄Mochudi的15-49岁人群进行全面的行为和生物医学干预，包括（1）常规的、选择退出的HIV检测;（2）鼓励行为改变的教育，包括使用避孕套;（3）男性包皮环切术;（4）针对急性感染和/或高病毒载量（VL）的HIV感染者的三种药物HAART。我们将在实施干预措施前后对莫丘迪的全体人口进行反复筛查，以确定艾滋病毒的流行率和发病率。接受艾滋病毒检测、使用避孕套和其他行为建议的情况将通过对整个村庄的重复调查进行评估。将在莫丘迪东北部（人口14 000人）评价其他干预措施的使用情况以及使用PCR和接触者追踪调查的事件感染来源。将进行病毒基因分型，以通过感染个体的序列分析识别潜在的病毒网络或簇。将建立数学模型并将其参数化，以反映Mochudi的流行情况，并根据监测活动提供的信息加以更新。这些模型将用于确定预防措施之间的潜在协同作用，并估计必须达到什么样的覆盖率/吸收率和有效性的综合水平，才能将病毒在社区中的有效繁殖数保持在1以下。具体目标是：（1）通过估计21/2年期间3个时间点的艾滋病毒和行为风险因素的发病率和流行率，确定Mochudi的艾滋病毒流行情况;（2）确定自愿咨询和检测的接受情况、安全套的使用情况、通过追踪接触者通知伴侣的可接受性以及男性包皮环切术;（3）用基因组签名追踪鉴定传播关联以评估传播与高VL之间的关联;（4）估计在检测到患有急性感染和/或VL e 100的HIV感染个体时提供的HAART的接受率，000名根据国家准则不符合治疗条件的人（艾滋病定义疾病或CD 4 < 250），并评估对药物时间表的依从性以及基线和新的耐药性的比率;以及（5）对流行病控制的潜力进行基于模型的预测和评估，并使用这些模型来评估预防干预措施组合的成本效益。博茨瓦纳Mochudi的艾滋病毒预防计划相关性该申请的目标是证明一项综合干预计划的可行性和可接受性，以减少Mochudi的艾滋病毒发病率，Mochudi是博茨瓦纳南部一个拥有39 000人的村庄，成年人的艾滋病毒感染率为25%。这种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。最终目标是评估可作为博茨瓦纳和南部非洲公共卫生政策扩大的预防干预措施。

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.