Drug-resistance testing in Kenya to improve ART suppression of HIV replication

肯尼亚的耐药性检测可改善 ART 对 HIV 复制的抑制

• 批准号: 8488409
• 负责人: Lisa M Frenkel
• 金额: $ 78.01万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-13 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488409
• 关键词: Adult; Africa; African; Anti-Retroviral Agents; Antiretroviral resistance; Asians; Biological Assay; CD4 Positive T Lymphocytes; Caring; Case-Control Studies; Child; Chronic; Clinical; Communities; Consensus Sequence; Country; Detection; Dose; Drug resistance; Effectiveness; Enrollment; Failure; Goals; HIV; HIV Infections; HIV drug resistance; HIV-1 drug resistance; Health; Human; Individual; Infant; Infection; Informed Consent; Intervention; Kenya; Laboratories; Lamivudine; Ligation; Longevity; Medicine; Modeling; Mothers; NNRTI-resistance; Nevirapine; Oligonucleotides; Outcome; Participant; Patients; Performance; Persons; Plasma; Population; Prevalence; Protease Inhibitor; Qualifying; RNA; Randomized; Reagent; Reproducibility; Resistance; Retrospective Studies; Sexual Partners; Shipping; Ships; Site; Specimen; Testing; Time; Training; Vertical Disease Transmission; Viral; Woman; Zidovudine; antiretroviral therapy; arm; base; care seeking; clinically significant; cohort; cost; cost effective; cost effectiveness; improved; innovation; mutant; nevirapine resistance; non-nucleoside reverse transcriptase inhibitors; pressure; prevent; programs; prospective; quality assurance; routine care; transmission process; trend

DESCRIPTION (provided by applicant): Durable suppression of HIV replication is critical to (1) improving the health of infected individuals, (2) to reducing HIV transmission to sexual partners and from mothers to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART. Across multiple trials, individuals with NNRTI-resistance, even at low-concentrations, have substantially greater virologic failure when treated with NVP vs. PI-ART. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections. A simple low-cost innovative assay we developed and successfully transferred to Asian and African countries (oligonucleotide ligation assay (OLA)) can detect NNRTI+lamivudine (3TC) resistant HIV using reagents that costs <$7.00/person. Furthermore, detection of NNRTI-resistance by OLA is highly (P<0.001) associated with virologic failure of nevirapine (NVP)-ART in two retrospective studies; one of Thai women who had been previously randomized to single-dose NVP and the second of ARV-na¿ve Kenyan adults. Implementation of OLA into routine care we hypothesize will allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and improve rates of durable suppression of viral replication, and thus improve CD4 cell gains and individuals' health, reduce the transmission of ARV-resistant HIV within the community, and maintain the utility of NNRTI-ART. In addition, we hypothesize that programmatically OLA-guided ART will be more cost-efficient compared to the current strategy of empiric use of NNRTI-ART as initial treatment. Here we propose to gauge improvements in the rate of durable suppression of viral replication by ART when OLA is used to guide clinical decisions at the PEPFAR Coptic Hope Center in Kenya, and to determine the cost-effectiveness of implementing this strategy at Coptic Hope Center.

描述（由申请人提供）：持久抑制艾滋病毒复制对以下方面至关重要：(1)改善感染者的健康状况；(2)减少艾滋病毒传染给性伴侣和母亲传染给婴儿；(3)维持目前第一线的有效性