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：
8672592
负责人：
Lisa M Frenkel
金额：
$ 134.75万
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 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8672592
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.

描述（由适用提供）：持久抑制艾滋病毒复制对于（1）改善感染者的健康，（2）以减少向性伴侣的艾滋病毒传播以及从母亲到婴儿的传播，以及（3）维持当前第一线的有效性基于非核苷逆转录酶抑制剂（NNRTI）的ART。在多个试验中，当用NVP与Pi-Art处理时，具有NNRTI抗性的个体，即使在低浓度时也具有更大的病毒衰竭。需要一种具有成本效益的策略来检测和管理对ARV抗ARV的HIV感染。我们开发并成功地转移到亚洲和非洲国家（寡核苷酸连接测定法（OLA））的一个简单的低成本创新测定法可以使用费用<$ 7.00/人的耐药试剂来检测NNRTI+Lamivudine（3TC）耐药HIV。此外，在两项回顾性研究中，OLA对NNRTI抗性的检测与奈韦拉平（NVP） - ART的病毒学衰竭相关（p <0.001）。以前曾经被随机分配给单剂量NVP的泰国妇女之一，而肯尼亚成年人则是第二剂。我们假设将OLA实施为常规护理，将使肯尼亚临床医生适当针对蛋白质抑制剂（PI）的ART，并提高病毒复制的持久抑制速度，从而改善CD4细胞的增长和个人健康，减少社区中ARV抗性HIV的传播，并维持Nnrti-Art的实用性。此外，我们假设与当前使用NNRTI-ART作为初始处理的经验使用策略相比，编程性OLA指导的ART将更具成本效益。在这里，我们建议在肯尼亚的Pepfar Coptic Hope中心指导ART抑制病毒复制的持久抑制速度，并确定在Coptic Hope Center实施此策略的成本效益。