Antiretroviral Therapy for HIV-2 Infection in Senegal

描述（由申请人提供）：本提案的总体目标是进一步了解强效抗逆转录病毒治疗（ART）对人类免疫缺陷病毒2型（HIV-2）感染的影响。HIV-2的致病性通常低于HIV-1。与HIV-1相比，HIV-2感染的特点是无症状期更长，血浆病毒载量更低，CD4+ T细胞计数下降更慢，艾滋病死亡率降低，母婴传播率降低，性传播率降低。尽管如此，很大比例的2型艾滋病毒感染者最终发展为艾滋病。在资源有限的环境中，抗逆转录病毒治疗越来越容易获得。在发现艾滋病毒-1和艾滋病毒-2的塞内加尔，制定了一项国家方案，为CD4+ T细胞计数低于200/mm3或CD4+ T细胞计数低于350/mm3的艾滋病患者提供抗逆转录病毒治疗（ART），并出现临床症状。然而，ART对HIV-2感染者的预后、免疫反应、病毒载量、动态和进化、HIV-2耐药性和适应性的影响在很大程度上是未知的。我们对来自塞内加尔达喀尔的HIV-2感染受试者进行了长期的纵向队列研究，为研究抗逆转录病毒治疗在抑制HIV-2感染方面的作用提供了独特的机会。本建议的具体目的是：目的1：确定纵向前瞻性HIV-2感染塞内加尔队列中与抗逆转录病毒治疗（ART）相关的临床、病毒学和免疫学结果。目的2：评估在病毒学失败的HIV-2感染对象中出现的耐药病毒的作用，并确定HIV-2和HIV-1之间出现的耐药病毒是否存在定性和定量差异。

DESCRIPTION (provided by applicant): The overarching goals of this proposal are to further our understanding of the effect of potent antiretroviral therapy (ART) on Human Immunodeficiency Virus Type 2 (HIV-2) infection. HIV-2 is generally less pathogenic than HIV-1. Compared to HIV-1, HIV-2 infection is characterized by a much longer asymptomatic stage, lower plasma viral loads, slower decline in CD4+ T cell count, decreased mortality rate due to AIDS, lower rates of mother to child transmission, and lower rates of sexual transmission. Nonetheless, a significant proportion of HIV-2 infected individuals eventually progress to AIDS. Antiretrov'iral therapy is becoming increasingly available in resource-limited settings. In Senegal where both HIV-1 and HIV-2 are found, a national program of providing antiretroviral treatment (ART) for those with AIDS, CD4+ T cell counts less than 200/mm3, or CD4+ T cell counts less than 350/mm3 and clinical symptoms has been established. However, the effects of ART on outcome, immunologic response, viral load, dynamics and evolution, HIV-2 drug resistance and fitness in HIV-2 infected individuals are largely unknown. Our longstanding longitudinal cohort of HIV-2 infected subjects from Dakar, Senegal provides a unique opportunity to study the role ART plays in suppressing HIV-2 infection. The Specific Aims of this proposal are: AIM 1: To determine the clinical, virologic and immunologic outcomes associated with antiretroviral therapy (ART) in a longitudinal prospective HIV-2 infected Senegalese cohort. AIM 2: To assess role of drug resistance in viruses that emerge in HIV-2 infected subjects with virologic failure and to determine if there are qualitative and quantitative differences the drug resistant viruses that emerge between HIV-2 and HIV-1.