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

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向性伴侣和母亲向其婴儿的传播，以及（3）维持当前一线治疗的有效性至关重要。 非核苷类逆转录酶抑制剂（NNRTI）为基础的ART。在多项试验中，具有NNRTI耐药的个体，即使在低浓度下，当用NVP与PI-ART治疗时，具有显著更大的病毒学失败。需要一种具有成本效益的策略来检测和管理ARV耐药的HIV感染。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方法（寡核苷酸连接检测（奥拉））可以检测NNRTI+拉米夫定（3 TC）耐药HIV，使用的试剂成本<7美元/人。此外，在两项回顾性研究中，奥拉检测到的NNRTI耐药与奈韦拉平（NVP）-ART的病毒学失败高度相关（P<0.001）;一项是先前随机接受单剂量NVP的泰国女性，另一项是ARV初治的肯尼亚成年人。我们假设，将奥拉应用于常规护理将使肯尼亚临床医生能够适当地靶向基于蛋白酶抑制剂（PI）的ART，并提高病毒复制的持久抑制率，从而改善CD 4细胞获得和个人健康，减少抗逆转录病毒药物耐药HIV在社区内的传播，并维持NNRTI-ART的效用。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，计划性OLA指导的ART将更具成本效益。在这里，我们建议，以衡量改善率的持久抑制病毒复制的抗逆转录病毒疗法时，奥拉是用来指导临床决策的总统艾滋病紧急救援计划科普特希望中心在肯尼亚，并确定实施这一战略的成本效益科普特希望中心。 公共卫生相关性：一种“鸡尾酒”药物可以治疗艾滋病毒感染，将其从致命感染转变为慢性感染。艾滋病毒对这些药物的抗药性在非洲似乎正在增加，并可能破坏治疗。将在肯尼亚采用一种廉价的简单检测艾滋病毒抗药性的方法。我们将研究这种检测方法对改善感染者健康的益处，并比较使用和不使用这种检测方法的总体成本。

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.