Drug Resistance and Pathogenesis in Subtype C HIV-1

C 亚型 HIV-1 的耐药性和发病机制

• 批准号: 7208025
• 负责人: David Allenberg Katzenstein
• 金额: $ 31.67万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208025
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Aftercare; Anti-Retroviral Agents; Antiretroviral drug resistance; Birth; Blood; Caring; China; Clinical; Complex; Country; Cross-Sectional Studies; DNA; Developed Countries; Developing Countries; Disease Progression; Dose; Drug resistance; Effectiveness; Ethiopia; Evolution; Exposure to; Failure; Frequencies; Gagging; Genes; Giant Cells; HIV; HIV Infections; HIV-1; HIV-1 Reverse Transcriptase; High Prevalence; Highly Active Antiretroviral Therapy; Human Milk; Incidence; India; Infant; Infection; Label; Lamivudine; Life; Medical Surveillance; Minority; Mutation; Nevirapine; Pathogenesis; Patients; Pattern; Pharmaceutical Preparations; Phase; Phenotype; Phylogeny; Plasma; Population; Predisposition; Prevalence; Prevention; Principal Investigator; RNA-Directed DNA Polymerase; Resistance; Resources; Reverse Transcriptase Inhibitors; Safety; Southern Africa; Surveys; Tenofovir; Thinking; Treatment Protocols; Tropism; Vertical Disease Transmission; Viral Drug Resistance; Virus; Week; Woman; Zidovudine; antiretroviral therapy; chemokine receptor; cohort; drug resistant virus; intrapartum; mortality; pol genes; virus tropism

DESCRIPTION (provided by applicant): AIDS care and treatment initiatives are anticipated to provide antiretroviral (ARV) treatment for 3 million people living with HIV/AIDS (PLWHA) in resource limited countries by 2005, the majority is infected by subtype C HIV-1, a widely dispersed virus responsible for HIV-1 infection in high prevalence populations in Southern Africa, Ethiopia, India and China. Reverse transcriptase inhibitor (RTI) ARV drugs, currently recommended as first-line therapy for HIV infection, are widely used in prevention of mother-to-child transmission (MTCT) as short-course regimens or single dose Nevirapine (SD NVP). Although SD NVP reduces MTCT by approximately 50%, rapid, complex selection of drug resistant virus has been documented in the majority of subtype C infected women and infected infants exposed to SD NVP. While drug resistant virus disappears (as detected by sequencing) from plasma RNA, archival resistant proviral DNA persists is thought to persist, potentially for years following exposure to NVP and other antiretroviral drugs (ARV). ARV therapy is expected to dramatically increase in developing countries, and viral drug resistance evolution will inevitably take place. Viruses from patients exposed to ARV drugs demonstrate phenotypic changes in drug susceptibility and envelope chemokine receptor tropism. Resistance to ARV drugs and the syncytia inducing (SI) phenotype are associated with distinct genotypic mutations in gag-pol and the V-3 loop of the env gene, respectively. These phenotypes are associated with rapid disease progression and mortality in HIV-1. The aim is to study the pathogenesis of subtype C HIV-1 in women and infants after ARV including SD NVP to optimize clinical benefits of ARV treatment and prevention of MTCT.

描述(由申请人提供)：艾滋病护理和治疗计划预计将为资源有限的国家的300万艾滋病毒/艾滋病患者提供抗逆转录病毒治疗。到2005年，大多数人感染C亚型艾滋病毒-1，这是一种广泛传播的病毒，导致艾滋病毒-1在南部非洲、埃塞俄比亚、印度和中国的高发人群中感染。逆转录酶抑制(RTI)抗逆转录病毒药物目前被推荐为HIV感染的一线治疗药物，被广泛用于预防母婴传播(MTCT)，作为短程方案或单剂量奈韦拉平(SD NVP)。尽管SD NVP使MTCT降低了约50%，但在大多数接触SD NVP的C亚型感染妇女和感染婴儿中，已经记录到对耐药病毒的快速、复杂的选择。虽然耐药病毒从血浆RNA中消失(通过测序检测)，但档案耐药前病毒DNA被认为持续存在，可能会在接触NVP和其他抗逆转录病毒药物(ARV)后持续数年。预计抗逆转录病毒治疗在发展中国家将大幅增加，病毒耐药性的演变将不可避免地发生。接触ARV药物的患者的病毒表现出药物敏感性和包膜趋化因子受体趋向性的表型变化。对ARV药物的耐药性和合胞体诱导(SI)表型分别与env基因的Gag-Poll和V-3环的不同基因突变有关。这些表型与HIV-1的疾病快速发展和死亡率有关。其目的是研究包括SD NVP在内的母婴ARV后C亚型HIV-1的发病机制，以优化ARV治疗和预防MTCT的临床效益。