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于(1)改善感染者的健康至关重要，(2)对于减少性伴侣和母亲向其婴儿传播艾滋病毒至关重要，(3)对于维持现有一线的有效性至关重要 基于非核苷类逆转录酶抑制剂(NNRTI)的抗逆转录病毒治疗。在多项试验中，具有NNRTI耐药性的个体，即使在低浓度下，在使用NVP与PI-ART治疗时，病毒学失败的程度也要大得多。需要一种具有成本效益的战略来检测和管理具有抗逆转录病毒能力的艾滋病毒感染。我们开发并成功转移到亚洲和非洲国家的一种简单、低成本的创新方法(寡核苷酸连接试验(OLA))可以使用每人7.00美元的试剂检测NNRTI+拉米夫定(3TC)耐药艾滋病毒。此外，在两项回顾性研究中，OLA检测NNRTI耐药性与奈韦拉平-ART的病毒学失败高度相关(P&lt；0.001)；一名泰国妇女之前被随机接受单剂NVP治疗，第二名肯尼亚成年人接受抗逆转录病毒治疗。我们假设，将OLA实施到常规护理中将使肯尼亚临床医生能够适当地针对基于蛋白酶抑制剂(PI)的ART，并提高持久抑制病毒复制的比率，从而改善CD4细胞数量和个人健康，减少抗ARV艾滋病毒在社区内的传播，并保持NNRTI-ART的效用。此外，我们假设，与目前经验性使用NNRTI-ART作为初始治疗的策略相比，程序化OLA引导的ART将更具成本效益。在这里，我们建议衡量在肯尼亚的PEPFAR科普特希望中心使用OLA指导临床决策时，ART持久抑制病毒复制的速度的改善，并确定在科普特希望中心实施这一策略的成本效益。