Antiretroviral Therapy for HIV-2 Infection in Senegal

塞内加尔针对 HIV-2 感染的抗逆转录病毒治疗

• 批准号: 8294927
• 负责人: Geoffrey Scott Gottlieb
• 金额: $ 68.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-07 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8294927
• 关键词: AIDS-Related Opportunistic Infections; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adherence; Adult; Adverse effects; Affect; Africa; Algorithms; Amprenavir; Anti-Retroviral Agents; Antiretroviral resistance; Applications Grants; Atazanavir; Attenuated; Base Sequence; Biological Assay; CCR1 gene; CCR5 gene; CD3 Antigens; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; CD8B1 gene; CXCR4 gene; CXCR6 gene; Caring; Cell Count; Cell Culture Techniques; Cells; Cessation of life; Characteristics; Clinical; Clinical Management; Collaborations; DNA; Data; Databases; Disease; Dose; Drug resistance; Drug-sensitive; Epidemiology; Event; Exposure to; Failure; Frequencies; Gambia; Genes; Genetic; Genital system; Genotype; Goals; Grant; Growth; HIV; HIV-1; HIV-2; Immune; Immunologics; In Vitro; Indinavir; Individual; Infection; Integrase; Integrase Inhibitors; International; Ivory Coast; Logistic Regressions; Mali; Measures; Methods; Minor; Minority; Molecular Cloning; Mutation; NNRTI-resistance; Natural History; Needs Assessment; Nelfinavir; Nigeria; Outcome; Pathway interactions; Patients; Pattern; Peptide Hydrolases; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Phenotype; Plasma; Population; Predisposition; Protease Gene; Protease Inhibitor; RNA; RNA-Directed DNA Polymerase; Randomized Controlled Trials; Regimen; Regression Analysis; Research; Resistance; Resources; Risk; Sampling; Secondary to; Senegal; Sexual Transmission; Site; Site-Directed Mutagenesis; Staging; Survival Analysis; Symptoms; T-20; T-Lymphocyte Subsets; Testing; Time; Toxic effect; Treatment outcome; Universities; Variant; Vertical Disease Transmission; Viral; Viral Load result; Virus; Washington; antiretroviral therapy; base; cohort; cross reactivity; effectiveness measure; evidence base; fitness; follow-up; inhibitor/antagonist; meetings; mortality; non-nucleoside reverse transcriptase inhibitors; population based; pressure; programs; prospective; public health priorities; public health relevance; receptor; reconstitution; resistance mutation; response; tipranavir

DESCRIPTION (provided by applicant): The overarching goals of our renewal proposal are to develop an integrated program to further our ability to provide evidenced-based, potent antiretroviral therapy (ART) to patients with HIV-2 infection. Compared to HIV-1, HIV-2 infection is characterized by a longer asymptomatic stage, lower plasma viral loads, slower decline in CD4 count, decreased mortality rate due to AIDS, lower rates of mother to child transmission, and lower rates genital shedding and sexual transmission. In West Africa, where both HIV-1 and HIV-2 co- circulate, between 1-2 million individuals are infected with HIV-2 and a significant proportion are co-infected with both HIV-1 and HIV-2. Despite the relatively attenuated disease course of HIV-2, a significant minority of untreated individuals will progress to clinical AIDS or death without ART and as will the majority of those dually infected with HIV-1 and HIV-2. Through local and global initiatives, antiretroviral therapy is becoming increasingly available in resource-limited West Africa. Because HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and may have partial resistance to some protease inhibitors (PI), treating HIV-2 and HIV-1/HIV-2 dual infection presents distinct challenges. This is especially problematic in resource-limited settings where there is limited choice and availability of 1st- line NRTI-PI based regimens as well as subsequent 2nd- line and salvage regimens in those individuals with clinical progression, immuno-virologic failure or antiretroviral (ARV) toxicities. During the initial period of our grant proposal we (and others) have made substantial progress in furthering our understanding ART for HIV-2 in ARV-naove adults as well as HIV-2 ARV-resistance. However, to date, we remain largely ignorant about the long-term outcomes of ART in HIV-2 infected people, we are in urgent need for assessment of new classes antiretrovirals for HIV-2 and we lack even rudimentary studies on ARV-regimens to treat HIV-1/HIV-2 dual infection, or whether ARV treatment outcomes using NRTI-PI based regimens are different than HIV-2 single infection. Our Renewal proposal has the following specific aims: AIM 1: Long-term outcomes of ART for HIV-2 infection in Senegal: Determine long- term HIV/AIDS associated outcomes and ARV-associated complications in HIV-2 infected individuals treated with ART for >2 years. Assessment of the frequency, causes and outcomes of switching to 2nd line and salvage ARV regimens for HIV-2 infection. AIM 2: To determine the potential utility and susceptibility of HIV-2 to new ARV classes: the integrase inhibitors and the CCR5 co-receptor entry inhibitors. AIM 3: To compare the clinical, virologic and immunologic outcomes associated with ART using NRTI+PI based regimens in a longitudinal prospective cohort of 50 HIV-1/HIV-2 dually infected ARV-naove subjects and a longitudinal prospective cohort of 50 HIV-2 ARV-naove singly infected subjects. Our Renewal proposal will build on a strong ongoing collaboration between the University of Washington and the Universite Cheikh Anta Diop de Dakar, Senegal to further our understanding and provide evidence-based ART and care for HIV-2 infected people. PUBLIC HEALTH RELEVANCE: In West Africa, two distinct AIDS viruses (HIV-1 and HIV-2) are found, and some people become infected by both types. Because HIV-1 and HIV-2 infection have different natural histories (with HIV-2 being less aggressive) and different antiretroviral drug susceptibilities (with HIV-2 being more drug resistant), treatment for HIV-2 and dual HIV-1/HIV-2 infection is clinically challenging. Understanding how to better treat HIV-2 and dual HIV-1/HIV-2 infection is an import public health priority in West Africa.

描述（由申请人提供）：我们更新提案的总体目标是制定一项综合计划，以进一步提高我们为 HIV-2 感染患者提供基于证据的有效抗逆转录病毒治疗 (ART) 的能力。与HIV-1相比，HIV-2感染的特点是无症状期较长、血浆病毒载量较低、CD4计数下降较慢、艾滋病死亡率降低、母婴传播率较低、生殖器脱落率和生殖器脱落率较低。性传播。在 HIV-1 和 HIV-2 共同传播的西非，有 1-200 万人感染 HIV-2，其中很大一部分人同时感染 HIV-1 和 HIV-2。尽管 HIV-2 的病程相对较弱，但相当少数未经治疗的个体将在没有 ART 的情况下发展为临床艾滋病或死亡，大多数同时感染 HIV-1 和 HIV-2 的个体也会如此。通过地方和全球举措，抗逆转录病毒疗法在资源有限的西非变得越来越可用。由于 HIV-2 本质上对非核苷类逆转录酶抑制剂具有耐药性，并且可能对某些蛋白酶抑制剂 (PI) 具有部分耐药性，因此治疗 HIV-2 和 HIV-1/HIV-2 双重感染面临着独特的挑战。这在资源有限的环境中尤其成问题，因为对于那些出现临床进展、免疫病毒学失败或抗逆转录病毒（ARV）治疗的个体，基于 NRTI-PI 的一线治疗方案以及随后的二线和挽救方案的选择和可用性有限。 ）毒性。在我们的资助提案的初始阶段，我们（和其他人）在进一步了解未接触过 ARV 的成人中的 HIV-2 ART 以及 HIV-2 ARV 耐药性方面取得了实质性进展。然而，迄今为止，我们对 ART 对 HIV-2 感染者的长期结果仍然一无所知，我们迫切需要评估新类别的 HIV-2 抗逆转录病毒药物，而且我们甚至缺乏关于 ARV 治疗方案的初步研究治疗 HIV-1/HIV-2 双重感染，或者使用基于 NRTI-PI 的方案的 ARV 治疗结果是否与 HIV-2 单一感染不同。我们的更新提案有以下具体目标： 目标 1：塞内加尔 ART 治疗 HIV-2 感染的长期结果：确定接受 ART 治疗的 HIV-2 感染者的长期 HIV/AIDS 相关结果和 ARV 相关并发症>2 年。评估针对 HIV-2 感染转用二线治疗和挽救性 ARV 治疗方案的频率、原因和结果。目标 2：确定 HIV-2 对新 ARV 类别的潜在效用和敏感性：整合酶抑制剂和 CCR5 辅助受体进入抑制剂。目标 3：在 50 名 HIV-1/HIV-2 双重感染 ARV 初治受试者的纵向前瞻性队列和由 50 名 HIV-1 受试者组成的纵向前瞻性队列中，比较使用基于 NRTI+PI 方案的 ART 相关的临床、病毒学和免疫学结果。 2 名未接触过 ARV 的单一感染者。我们的更新提案将建立在华盛顿大学和塞内加尔达喀尔谢赫安塔迪奥普大学之间持续不断的强有力合作的基础上，以进一步加深我们的了解，并为 HIV-2 感染者提供循证的 ART 和护理。 公共卫生相关性：在西非，发现了两种不同的艾滋病病毒（HIV-1 和 HIV-2），有些人同时感染这两种病毒。由于 HIV-1 和 HIV-2 感染具有不同的自然史（HIV-2 侵袭性较低）和不同的抗逆转录病毒药物敏感性（HIV-2 耐药性更强），因此针对 HIV-2 和双重 HIV-1/HIV 的治疗-2感染在临床上具有挑战性。了解如何更好地治疗 HIV-2 和 HIV-1/HIV-2 双重感染是西非重要的公共卫生优先事项。