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: 8469814
• 负责人: Geoffrey Scott Gottlieb
• 金额: $ 63.89万
• 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/8469814
• 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.

描述（由申请人提供）：我们的更新提案的总体目标是制定一个综合计划，以进一步提高我们为HIV-2感染患者提供循证有效的抗逆转录病毒治疗（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，CD 4计数下降较慢，艾滋病死亡率下降，母婴传播率较低，生殖器脱落和性传播率较低。在HIV-1和HIV-2共同传播的西非，有100万至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，但在没有抗逆转录病毒治疗的情况下，相当一部分未经治疗的个体将进展为临床艾滋病或死亡，大多数双重感染HIV-1和HIV-2的人也是如此。通过地方和全球举措，资源有限的西非越来越多地提供抗逆转录病毒疗法。由于HIV-2本身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双重感染存在明显的挑战。这在资源有限的情况下尤其成问题，在这些情况下，在具有临床进展、免疫病毒学失败或抗逆转录病毒（ARV）毒性的那些个体中，一线基于NRTI-PI的方案以及后续二线和挽救方案的选择和可用性有限。在我们的赠款提案的最初阶段，我们（和其他人）在进一步了解ART治疗ARV-naove成人中的HIV-2以及HIV-2 ARV耐药性方面取得了实质性进展。然而，到目前为止，我们仍然在很大程度上不了解ART在HIV-2感染者中的长期结果，我们迫切需要评估针对HIV-2的新型抗逆转录病毒药物，我们甚至缺乏对治疗HIV-1/HIV-2双重感染的ARV方案的初步研究，或者使用基于NRTI-PI的方案的ARV治疗结果是否不同于HIV-2单一感染。我们的更新提案有以下具体目标：目标1：塞内加尔艾滋病毒2型感染者抗逆转录病毒疗法的长期结果：确定接受抗逆转录病毒疗法治疗超过2年的艾滋病毒2型感染者的长期艾滋病毒/艾滋病相关结果和抗逆转录病毒相关并发症。评估HIV-2感染转为二线和补救ARV方案的频率、原因和结局。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CCR 5共受体进入抑制剂。目标3：在50例HIV-1/HIV-2双重感染ARV-nove受试者和50例HIV-2 ARV-nove单一感染受试者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、病毒学和免疫学结局。我们的更新提案将建立在华盛顿大学和塞内加尔达喀尔大学之间正在进行的强有力的合作基础上，以进一步加深我们的理解，并为HIV-2感染者提供基于证据的ART和护理。