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: 8298850
• 负责人: Lisa M Frenkel
• 金额: $ 93.47万
• 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/8298850
• 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. PUBLIC HEALTH RELEVANCE: A "cocktail" of medicines can treat HIV infection, transforming it from a lethal to a chronic infection. HIV - resistance to these medicines appears to be increasing in Africa and can undermine treatment. An inexpensive simple assay to detect HIV drug-resistance will be implemented in Kenya. We will study the benefits conferred by this assay to improving infected individuals health, and compare the overall cost of using to not using this test.

描述（由申请人提供）：持久抑制 HIV 复制对于 (1) 改善感染者的健康，(2) 减少 HIV 传播给性伴侣以及从母亲传播给婴儿，以及 (3) 维持当前第一线药物的有效性至关重要 基于非核苷逆转录酶抑制剂 (NNRTI) 的 ART。在多项试验中，对 NNRTI 耐药的个体，即使在低浓度下，接受 NVP 治疗时的病毒学失败率也明显高于 PI-ART 治疗。需要一种具有成本效益的策略来检测和管理抗逆转录病毒药物艾滋病毒感染。我们开发了一种简单的低成本创新检测方法，并成功转移到亚洲和非洲国家（寡核苷酸连接检测（OLA）），可以使用每人成本低于 7.00 美元的试剂检测 NNRTI+拉米夫定 (3TC) 耐药性 HIV。此外，在两项回顾性研究中，OLA 检测到的 NNRTI 耐药性与奈韦拉平 (NVP)-ART 的病毒学失败高度相关 (P<0.001)。其中一位是之前被随机分配接受单剂 NVP 的泰国妇女，另一位是未接受过抗逆转录病毒治疗的肯尼亚成年人。我们假设将 OLA 纳入常规护理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 并提高病毒复制的持久抑制率，从而改善 CD4 细胞增益和个人健康，减少社区内抗 ARV 病毒的传播，并维持 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，以程序化 OLA 引导的 ART 将更具成本效益。在这里，我们建议评估当 OLA 用于指导肯尼亚 PEPFAR 科普特希望中心的临床决策时，ART 持久抑制病毒复制的速度的改善情况，并确定在科普特希望中心实施这一策略的成本效益。 公共卫生相关性：药物“鸡尾酒”可以治疗艾滋病毒感染，将其从致命性感染转变为慢性感染。在非洲，艾滋病毒对这些药物的耐药性似乎正在增加，并可能破坏治疗。肯尼亚将实施一种廉价、简单的检测艾滋病毒耐药性的方法。我们将研究该检测对于改善感染者健康状况所带来的好处，并比较使用与不使用该检测的总体成本。