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

改善诊断、治疗

• 批准号: 10189489
• 负责人: Geoffrey Scott Gottlieb
• 金额: $ 73.39万
• 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/10189489
• 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; 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; Serology; 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制定了雄心勃勃的“90-90-90”目标（90% 的艾滋病毒感染者将了解自己的艾滋病毒状况， 90% 的艾滋病毒感染者将接受持续的抗逆转录病毒治疗，90% 的人将接受持续抗逆转录病毒治疗 接受抗逆转录病毒治疗将抑制病毒）并到 2030 年结束艾滋病流行。 为了实现这些目标，并最终结束艾滋病毒的流行，简单、安全、有效和有效的抗逆转录病毒疗法将是 艾滋病毒诊断和病毒载量监测所需的简单且廉价的护理点设备。 计划在全球推出基于多替拉韦的第一线 ART，采用通用的替诺福韦单片方案 拉米夫定-多替拉韦 (TLD) 的估计成本为 75 美元/年，有可能显着改变 资源有限环境（RLS）中艾滋病流行的过程。在西非/中非，约有 500 万人口 艾滋病毒感染者 (PLHIV) 每年约有 280,000 例新感染病例和约 160,000 例死亡，滞后于 90-90-90 目标 (64%, 51%, 39%) 无艾滋病一代的目标由于 HIV-1 和 HIV- 两种病毒在西非同时流行，每种病毒在诊断和抗逆转录病毒治疗 (ART) 方面都有各自的挑战。 目前，针对 HIV-2（以及 HIV-1/HIV-2 双重感染）的一线 ART 是替诺福韦-拉米夫定-洛匹那韦/利托那韦。 HIV-2 对 NNRTI 的内在耐药性。在西非推出顶级域名 (TLD) 有可能极大地改变现状 为 HIV-1 和 HIV-2 提供单一有效的一线 ART 治疗方案。塞内加尔 国家艾滋病计划（Initiative Senegalaise d’Acces aux ARV (ISAARV)）正在计划向 TLD 过渡 2020 年初针对 HIV-1、HIV-2 和 HIV-1/HIV-2 双重感染进行一线 ART。威斯康星大学塞内加尔研究 双方在 HIV-2 前沿转化和临床研究方面拥有 30 年的合作历史 与我们的塞内加尔合作伙伴一起治疗。更新我们当前的 R01，题为“改善诊断， HIV-2 感染耐药性的治疗和检测”，我们建议以我们之前的工作为基础 具体目标如下： 目标 1：确定临床和免疫病毒学结果（HIV 病毒学 失败 (VF)/病毒抑制 (VS) 率、HIV 耐药性 (DR)、CD4 计数、二线转换率 未接受过 ARV 治疗和经历过 ARV 治疗的 HIV-2 患者中的 ART、不良事件、OIs 和合并症、LTFU 和死亡 和 HIV-1/HIV-2 感染患者，在 ISARV 中新开始接受基于多替拉韦的 ART (TLD) 程序。目标 2：确定基因型和表型易感性、耐药机制和 HIV-2 转化为新型和正在研发的抗逆转录病毒药物的途径。 AIM 3：3A：验证和现场评估 塞内加尔的 POC m-PIMA HIV-1/2 病毒载量 (VL) 和检测测定。 3B：m-的实施试验 PIMA 临床吸收和利用，用于有关 HIV-2 和 HIV-1/HIV-2 VF 和 ART 的患者护理决策 ISARV 的管理。