Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 Infection

改善诊断、治疗

• 批准号: 10078744
• 负责人: Geoffrey Scott Gottlieb
• 金额: $ 75.48万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10078744
• 关键词: Acquired Immunodeficiency Syndrome; Adverse event; Africa; Anti-Retroviral Agents; Biological Assay; CD4 Lymphocyte Count; Capsid; Caring; Central Africa; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Death Rate; Devices; Diagnosis; Discrimination; Drug resistance; Effectiveness; Enrollment; Ensure; Epidemic; Europe; Evaluation; Failure; Generations; Genotype; Goals; Guidelines; HIV; HIV Infections; HIV diagnosis; HIV drug resistance; HIV serology; HIV-1; HIV-2; Home environment; Human immunodeficiency virus test; Infection; Integrase; Lamivudine; Lead; Lopinavir/Ritonavir; Modeling; Monitor; Multi-Drug Resistance; Nucleic Acids; Outcome; Participant; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Phenotype; Predisposition; Purines; Recording of previous events; Regimen; Research; Resistance; Resources; Sample Size; Senegal; Serologic tests; Site-Directed Mutagenesis; Tablets; Tenofovir; Testing; Treatment Protocols; Validation; Viral; Viral Load result; Visit; Work; antiretroviral therapy; arm; base; clinical decision-making; comorbidity; comparative; cost estimate; diagnostic assay; drug testing; experience; implementation trial; improved; inhibitor/antagonist; next generation; non-nucleoside reverse transcriptase inhibitors; novel; point of care; primary endpoint; programs; public health intervention; resistance mechanism; resistance mutation; secondary endpoint; tool; translational study; uptake; virology

The UNAIDS has set ambitious “90-90-90” targets (90% of all people living with HIV will know their HIV status, 90% of all people with diagnosed HIV infection will receive sustained antiretroviral therapy, 90% of all people receiving antiretroviral therapy will have viral suppression) and an end to the AIDS epidemic by 2030. To achieve these goals, and to eventually end the HIV epidemic, simple, safe, effective and potent ARV-regimens will be needed as well as simple and inexpensive, point-of-care devices for HIV diagnosis and viral load monitoring. The planned global rollout of a 1st-line dolutegravir based ART with a generic, single table regimen of tenofovir- lamivudine-dolutegravir (TLD) with an estimated cost of $75 (USD)/year has the potential the dramatically alter the course of the AIDS epidemic in resource limited settings (RLS). In West/Central Africa, home to ~5.0 million people living with HIV (PLHIV), ~280,000 new infections and ~160,000 deaths per year, and lagging 90-90-90 targets (64%, 51%, 39%) the goal of an AIDS free generation is complicated by the fact that both HIV-1 and HIV- 2 are co-circulating in West Africa, each with its’ own challenges for diagnosis and antiretroviral treatment (ART). Currently, 1st-line ART for HIV-2 (and dual HIV-1/HIV-2 infection) is tenofovir-lamivudine-lopinavir/ritonavir due to HIV-2’s intrinsic resistance to NNRTI. Rollout of TLD in West Africa has the potential to dramatically alter the treatment landscape by providing a single potent 1st-line ART regimen for both HIV-1 and HIV-2. The Senegal National AIDS Program (Initiative Senegalaise d’Acces aux ARV (ISAARV)) is planning for the transition to TLD for 1st line ART for HIV-1, HIV-2 and HIV-1/HIV-2 dual infections in early 2020. The UW-Senegal Research Collaboration has a 3 decades history of performing cutting edge translational and clinical studies of HIV-2 treatment with our Senegalese partners. For the Renewal of our current R01 entitled “Improving Diagnosis, Treatment & Detection of Drug Resistance in HIV-2 Infection” we propose to build on our previous work with the following Specific Aims: AIM 1: To determine the clinical and immuno-virologic outcomes (HIV virologic failure(VF)/viral suppression (VS) rates, HIV drug resistance (DR), CD4 counts, switch rates to 2nd-line ART, adverse events, OIs & co-morbidities, LTFU and death), in ARV-naïve and ARV-experienced HIV-2 and HIV-1/HIV-2 infected patients, newly initiated on dolutegravir-based ART (TLD) in the ISAARV program. AIM 2: Determination of genotypic and phenotypic susceptibility, resistance mechanisms and pathways, of HIV-2 to novel and pipeline antiretroviral agents. AIM 3: 3A: Validation & field evaluation of the POC m-PIMA HIV-1/2 Viral Load (VL) & Detect Assays in Senegal. 3B: An implementation trial of m- PIMA clinical uptake & utilization for patient care decisions regarding HIV-2 & HIV-1/HIV-2 VF & ART management in the ISAARV.

联合国艾滋病规划署设定了雄心勃勃的“ 90-90-90”目标（所有艾滋病毒患者中有90％都知道他们的艾滋病毒状况， 所有被诊断为HIV感染的患者中有90％将接受持续的抗逆转录病毒疗法，所有患者中有90％ 接受抗逆转录病毒疗法将受到病毒抑制），到2030年，艾滋病流行病终结。 这些目标，并最终结束艾滋病毒流行，简单，安全，有效和潜在的ARV剂量将是 需要以及简单且廉价的艾滋病毒诊断和病毒载荷监测设备。 计划的一条基于Dolutegravir的艺术的全球推出，具有通用的，单桌的替代方案 lamivudine-dolutegravir（TLD）估计成本为75美元（美元）/年的潜力很大变化 资源有限设置（RLS）中艾滋病流行的过程。在西非/中非，约有5000万 患有艾滋病毒（PLHIV）的人，约280,000个新感染和约160,000人死亡，滞后90-90-90 目标（64％，51％，39％）的目标是自由艾滋病的目标，这一事实使HIV-1和HIV-都复杂化。 2在西非共同循环，每个人都面临着对诊断和抗逆转录病毒治疗（ART）的挑战。 目前，HIV-2（和双HIV-1/HIV-2感染）的第一线艺术是Tenofovir-Lamivudine-lopinavir/Ritonavir HIV-2对NNRTI的固有抵抗力。在西非的TLD推出有可能极大地改变 通过为HIV-1和HIV-2提供单一潜在的一线艺术方案来处理景观。塞内加尔 国家艾滋病计划（塞内加拉利d'Acces Aux ARV（ISAARV））正在计划过渡到TLD 对于2020年初的HIV-1，HIV-2和HIV-1/HIV-2双重感染的第一线ART。 协作有30年的历史，用于进行HIV-2的尖端翻译和临床研究 与我们的塞内加尔合作伙伴进行治疗。为了续签我们目前的R01，标题为“改善诊断， HIV-2感染中耐药性的治疗和检测”我们建议以我们先前的工作为基础 以下具体目的：目标1：确定临床和免疫学结果（HIV病毒学） 衰竭（VF）/病毒抑制（VS）率，HIV耐药性（DR），CD4计数，转换速率为第二线 艺术，不良事件，OIS和合并症，LTFU和死亡） 和HIV-1/HIV-2感染的患者，在ISAARV的基于Dolutegravir的ART（TLD）上新启动 程序。目标2：确定基因型和表型敏感性，抗性机制和 HIV-2与新型抗逆转录病毒药物的途径。目标3：3a：验证和现场评估 POC M-PIMA HIV-1/2病毒载量（VL）和塞内加尔检测测定法。 3B：M-的实施试验 PIMA临床摄取和利用用于HIV-2和HIV-2/HIV-1/HIV-2 VF和ART的患者护理决定 Isaarv的管理。