Early Mortality in HIV Infected Patients Starting Antiretroviral Therapy in Afric

描述(申请人提供)：抗逆转录病毒疗法终于惠及非洲数百万艾滋病毒感染者。虽然拯救了无数人的生命，但越来越明显的是，与工业化环境相比，抗逆转录病毒治疗前6个月的死亡人数大幅上升--可能高达工业化环境下的五倍。然而，即使是这些令人震惊的估计也可能被低估了，因为在资源有限的情况下进行后续行动的高损失意味着许多死亡病例无法确定。此外，这些早期死亡的原因没有得到很好的解释。因此，拟议的目标是：(1)评估我们为了解早期死亡的真实程度而开发的基于抽样的技术；(2)通过收集生物学标本并在旧金山对其进行深入调查，确定未诊断的机会性感染是否是ART早期死亡的原因；以及(3)开发临床预测规则，以对个体患者在启动ART时的早期死亡进行风险分层。总体而言，这项研究试图了解非洲艾滋病毒感染者早期ART死亡率的大小和决定因素，以便在未来制定有针对性的干预措施，以减少这种情况。这些目标还将为完成进一步的职业发展提供平台，使其成为一名独立的科学家。 相关性：在非洲开始接受抗逆转录病毒治疗的数百万患者中，每10名患者中就有1人死于抗逆转录病毒治疗。这些死亡很可能是由于可治疗的感染。因此，更好地了解非洲抗逆转录病毒治疗的早期死亡率有可能改善抗逆转录病毒治疗的效果，挽救许多人的生命。

DESCRIPTION (provided by applicant): Antiretroviral therapy is finally reaching millions of persons with HIV infection in Africa. While countless lives have been saved, it is becoming increasingly clear that deaths in the first 6 months on ART are dramatically elevated as compared to industrialized settings, - perhaps claiming as many as five-fold more than in industrialized settings. Even these alarming estimates, however, are likely underestimates because high losses to follow up in resource limited settings mean that many deaths are not ascertained. The causes of these early deaths, furthermore, are not well explained. Therefore the proposed Aims seek to (1) evaluate a sampling-based technique that we have developed to understand the true magnitude of early mortality; (2) determine whether undiagnosed opportunistic infections are the cause of early mortality on ART by collecting biological specimens and investigating them intensively in San Francisco and (3) develop a clinical prediction rule to risk stratify individual patients for early mortality at the time or ART initiation. Overall, this study seeks to understand the magnitude and determinants of early mortality on ART in HIV infected patients in Africa in order to develop a targeted intervention in the future to reduce it. These Aims will also provide a platform for completing further career development toward independence as a scientist. RELEVANCE: Early mortality on ART may claim 1 in 10 patients of the millions of patients starting ART in Africa. These deaths are likely due to treatable infections. Therefore, a better understanding of early mortality on ART in Africa has the potential to improve ART delivery and save many lives.