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

改善诊断、治疗

• 批准号: 10652277
• 负责人: Geoffrey Scott Gottlieb
• 金额: $ 73.74万
• 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/10652277
• 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; Lopinavir/Ritonavir; Modeling; Monitor; Multi-Drug Resistance; Nucleic Acids; Outcome; Participant; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Persons; Phenotype; Predisposition; Recording of previous events; Regimen; Research; Resistance; Resource-limited setting; Sample Size; Senegal; Serology; Site-Directed Mutagenesis; Tablets; Tenofovir; Testing; Treatment Protocols; Validation; Viral; Viral Load result; Visit; Work; acceptability and feasibility; antiretroviral therapy; arm; clinical decision-making; comorbidity; comparative; cost estimate; detection assay; diagnostic assay; drug testing; experience; implementation trial; improved; inhibitor; 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; viral detection

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知道自己的艾滋病毒状况， 90%的确诊艾滋病毒感染者将接受持续的抗逆转录病毒治疗， 接受抗逆转录病毒治疗的人将得到病毒抑制），并在2030年前结束艾滋病流行。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治疗方案将是 需要以及简单和廉价的，用于艾滋病毒诊断和病毒载量监测的护理点设备。 计划在全球推出基于多替拉韦的一线ART，并采用替诺福韦的通用单表方案， 拉米夫定-度鲁特韦（拉米夫定），估计费用为75美元/年，有可能大大改变 艾滋病在资源有限环境中的流行过程。在西非/中非，约有500万人 艾滋病毒感染者（PLHIV），每年约有280，000例新感染和约160，000例死亡，并滞后于90-90-90 目标（64%，51%，39%），艾滋病毒-1和艾滋病毒- 两种病毒在西非共同传播，每种病毒在诊断和抗逆转录病毒治疗（ART）方面都有自己的挑战。 目前，HIV-2（和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的内在抗性。在西非推广生物多样性有可能极大地改变 通过为HIV-1和HIV-2提供单一有效的一线ART方案，改善了治疗前景。塞内加尔 国家艾滋病方案（塞内加尔艾滋病防治行动）正在计划向艾滋病方案过渡。 在2020年初为HIV-1、HIV-2和HIV-1/HIV-2双重感染提供一线抗逆转录病毒治疗。UW-Senegal研究 协作有30年的历史进行尖端的翻译和临床研究的艾滋病毒-2 我们的塞内加尔合作伙伴。为了更新我们目前的R 01，题为“改善诊断， 治疗和检测HIV-2感染的耐药性”我们建议在我们以前的工作基础上， 以下具体目标：目的1：确定临床和免疫病毒学结局（HIV病毒学 失败（VF）/病毒抑制（VS）率、HIV耐药（DR）、CD 4计数、转换至二线治疗率 ART、不良事件、OI和合并症、LTFU和死亡），未接受过抗逆转录病毒治疗和接受过抗逆转录病毒治疗的HIV-2 和HIV-1/HIV-2感染患者，在ISAARV中新开始接受基于度鲁特韦的ART（ART） 程序.目的2：确定基因型和表型敏感性，耐药机制和 途径，艾滋病毒-2的新的和管道抗逆转录病毒药物。目的3：3A：验证和现场评价 塞内加尔的POC m-PIMA HIV-1/2病毒载量（VL）和检测检测。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 ISAARV的管理。

项目成果

The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

核苷类似物 BMS-986001 的体外抗 HIV-2 活性高于抗 HIV-1。

• DOI: 10.1128/aac.01326-15
• 发表时间: 2015
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Smith,RobertA;Raugi,DanaN;Wu,VincentH;Leong,SallyS;Parker,KateM;Oakes,MariahK;Sow,PapaSalif;Ba,Selly;Seydi,Moussa;Gottlieb,GeoffreyS;UniversityofWashington-DakarHIV-2StudyGroup
• 通讯作者: UniversityofWashington-DakarHIV-2StudyGroup