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

基本信息

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
项目类别：
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

项目摘要

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) 保持有效性至关重要当前第一行的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，使用 NVP 治疗时的病毒学失败率也比 PI-ART 更高。我们开发并成功转移到亚洲和非洲国家的一种简单的低成本创新检测（寡核苷酸连接检测（OLA））可以检测和管理抗逆转录病毒药物感染。 NNRTI+拉米夫定 (3TC) 耐药性 HIV 使用成本低于 7.00 美元/人此外，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）。之前被随机分配接受单剂 NVP 和第二剂 ARV-na 的泰国女性的比例将 OLA 纳入我们参与的日常护理中将使肯尼亚圣人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，减少抗逆转录病毒药物 (ARV) 耐药性艾滋病毒在社区内的传播，并维持 NNRTI-ART 的效用。此外，我们追求以程序化 OLA 为指导的 ART 与目前的经验性使用策略相比更具成本效益。在此，我们建议在肯尼亚 PEPFAR 科普特希望中心使用 OLA 指导临床决策时，评估 ART 对病毒复制的持久抑制率的改善情况，并确定实施的成本效益。科普特希望中心的这一策略。公共卫生相关性：多种药物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，并且可能会破坏检测艾滋病毒药物的廉价简单检测方法。 -抵抗将在肯尼亚实施。我们将研究这种检测对改善感染者健康所带来的好处，并比较使用和不使用这种检测的总体成本。