Pregnancy and Response to Antiretroviral Therapy in South Africa

这项提案的总体目标保持不变，旨在调查在南非约翰内斯堡接受治疗的HIV-I妇女中怀孕对高效抗逆转录病毒疗法(HAART)反应的影响。此外，我们将继续开发这笔赠款的K99部分的培训部分中描述的先进的定量流行病学方法。 南非孕妇的艾滋病毒感染率大大高于其他成年人。尽管对预防艾滋病毒母婴传播的干预措施以及在干预期间和干预后对抗逆转录病毒治疗的反应进行了广泛的研究，但对怀孕本身对治疗反应和保留的影响知之甚少。充分了解怀孕对母体对HAART反应的影响，对于向非洲和其他地方的H1V妇女提供良好的临床护理至关重要。为了解决这些问题，这项工作建议检查怀孕对HAART的免疫反应，临床(艾滋病/死亡)对HAART的反应， 以及对HAART的坚持和对护理的保留。由于不可能(而且非常不道德)对怀孕的暴露情况进行随机化，这项研究将依赖于在南非约翰内斯堡的Themba Lethu诊所收集的高质量临床数据，该诊所是一家城市抗逆转录病毒治疗诊所，与威特沃特斯兰德大学的临床艾滋病毒研究单位有关。拟议工作的首席调查员Daniel Westreich博士在与临床研究人员和临床医生合作产生高质量研究方面有着良好的记录。对这些数据的分析将需要 采用结构模型、先进的身体流行病学方法。

The overall goal of this proposal remains unchanged and is to investigate the effect of pregnancy on response to highly active antiretroviral therapy (HAART) among HIV-i- women in treatment in Johannesburg, South Africa. In addition, we will continue developing the advanced quantitative epidemiologic methods described in the training component ofthe K99 portion of this grant. Prevalence of HIV among pregnant women in South Africa is substantially higher than that among other adults. Despite extensive study of interventions for the prevention of mother to child transmission of HIV, and response to antiretroviral therapy during and after such interventions, little is known about the effect of pregnancy itself on responses to and retention in therapy. Fully understanding the effect of pregnancy on maternal responses to HAART is essential to providing good clinical care to H1V+ women in Africa and elsewhere. To address these questions, this work proposes to examine the effect of pregnancy on immunologic responses to HAART, clinical (AIDS/death) responses to HAART, and to adherence to HAART and retention in care. Because it is impossible (and highly unethical) to randomize the exposure of pregnancy, this study will rely on high quality clinical data collected in the Themba Lethu Clinic in Johannesburg, South Africa, an urban antiretroviral therapy clinic associated with the Clinical HIV Research Unit at the University ofthe Witwatersrand. The Principal Investigator of the proposed work, Dr. Daniel Westreich, has a strong track record in producing high quality research in collaboration with investigators and clinicians at the Clinic. The analysis of these data will require the use of structural models, an advanced body of epidemiologic methods.