Anti-HIV Therapy in Senegal, West Africa

描述(申请人提供)：在过去的17年里，我们与哈佛大学公共卫生学院合作研究塞内加尔的艾滋病毒感染。我们发展了我们的临床和病毒学研究能力，以支持塞内加尔的国家抗逆转录病毒计划，该计划自1998年起生效。拟议的研究、基础设施发展和培训不仅将支持塞内加尔的国家抗逆转录病毒方案，还将提供适用于非洲环境的治疗方案的重要新数据。 1)抗逆转录病毒疗法的临床试验-塞内加尔是首批启动国家抗逆转录病毒计划的非洲国家之一，目前已有3-4年的经验和两项已完成的临床试验。我们建议继续这一努力，进行新的试点II期试验，以评估相对较新的三重核苷逆转录酶抑制物(NRTI)方案对HIV-1、HIV-2和双重感染一线治疗的安全性和有效性。还提出了替代方案，可为随后的对比试验和制定一系列可能适合艾滋病毒感染长期治疗的有效方案提供基础。在ARV试验的背景下提出的研究将寻求表征野生型逆转录酶和蛋白酶基因，并表征在药物压力和临床失败情况下发生的耐药突变的动态。其他研究将确定在有效的ARV治疗下HIV-2感染的病毒动力学，并将这些与我们对HIV-1 B亚型感染动力学的理解进行比较。 2)基础设施发展-我们将与参与抗逆转录病毒治疗的临床医生建立和加强合作，开发临床管理方法，以提高对治疗方案的依从性，并提供抗逆转录病毒临床试验的经验。我们将发展和增强我们的临床免疫学和病毒学能力，以更好地支持接受抗逆转录病毒治疗的艾滋病毒患者的临床管理。这将包括基于FACS的免疫学分析以及HIV-1和HIV-2的DNA和RNA定量聚合酶链式反应分析。通过与波士顿的合作，我们将为我们的实验室开发艾滋病毒测序能力。这将使通过体外和测序技术鉴定抗逆转录病毒病毒成为可能。 3)为更大规模的抗逆转录病毒项目提供培训。这一多学科项目需要许多训练有素的人员。我们将提出几个研讨会和培训奖学金，允许来自塞内加尔和西非其他地区的研究人员来到我们的实验室，接受抗逆转录病毒治疗项目的培训。这将包括有效管理抗逆转录病毒病毒所需的临床管理和实验室方法和实践。

DESCRIPTION (provided by applicant): Over the past 17 years, we have collaborated with the Harvard School of Public Health to study HIV infections in Senegal. We have developed our clinical and virologic research capacity to support the national ARV program in Senegal, now in effect since 1998. The proposed research, infrastructure development and training will not only support the National ARV program in Senegal, but provide important new data on treatment regimens applicable to the African setting. 1) Clinical trials of ARV therapy - Senegal was one of the first African nations to initiate a national ARV program, now with 3-4 years of experience and two completed clinical trials. We propose to continue this effort with new pilot phase II trials to evaluate the safety and efficacy of a relatively new triple nucleoside reverse transcriptase inhibitor (NRTI) regime for first line treatment of HIV-1, HIV-2 and dual infections. Alternative regimens are also proposed that may provide the basis for subsequent comparison trials and development of a sequence of efficacious regimes that may be amenable to long-term treatment of HIV infection. Research studies proposed within the context of the ARV trial will seek to characterize the wild type reverse transcriptase and protease genes and characterize the dynamics of drug resistant mutations that occur under drug pressure and clinical failure. Other studies will determine the viral dynamics of HIV-2 infection under potent ARV therapy and compare these to our understanding of HIV-1 subtype B infection dynamics. 2) Infrastructure development - We will establish and strengthen collaborations with clinicians involved in ARV therapy to develop methods of clinical management to enhance adherence to therapeutic regimes, and provide experience in clinical trials of ARV. We will develop and augment our clinical immunology and virology capabilities to better support the clinical management of HIV patients on ARV therapy. This will include FACs based immunologic assays and quantitative DNA and RNA PCR assays for HIV-1 and HIV-2. Through collaboration with Boston, we will develop HIV sequencing capabilities for our laboratories. This will allow for the identification of ARV resistant viruses through in vitro as well as sequence techniques. 3) Training for larger scale ARV programs. This multidisciplinary program will require many well Trained personnel. We will propose several workshops and training fellowships that will allow investigators from other parts of Senegal and West Africa to come to our laboratories to train in ARV therapy programs. This will include both clinical management and laboratory methods and practices required for effective ARV management.