A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc (VHM) in Controlling HIV After Treatment Interruption in Subjects Who Initiated ART During Acute HIV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Proportion of patients with HIV RNA < 50 copies/ml following ART interruption
研究概览
简要总结
This study is a two-arm prospective 1:1 randomised controlled trial comparing the proportion of patients between:
Group 1: vorinostat/hydroxychloroquine/maraviroc (VHM) co-administered with anti-retroviral therapy (ART) Group 2: ART only who are able to maintain HIV RNA < 50 copies/ml following treatment interruption. Subjects will be recruited from RV254/SEARCH 010, an acute HIV infection cohort conducted by the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. The study will run for a minimum of 34 weeks from screening.
详细描述
Study site:
This will be a single-center proof-of-concept study in which recruitment and follow-up of volunteers will be done at the Thai Red Cross AIDS Research Centre (TRC-ARC).
Subject Population:
Subjects aged 18-60 years old, who initiated ART during acute HIV infection and have maintained viral suppression (HIV RNA < 50 copies/ml) for at least 28 weeks prior will be asked to enroll in the study. The subjects must have CD4 ≥ 450 cells/µl, and EKG and laboratory values within acceptable ranges.
Sample Size:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infected adults 18-60 years
- •Initiated ART during acute HIV infection period, defined serologically as up to a positive but incomplete profile by Western blot and has been on ART for at least 42 weeks
- •HIV RNA <50 copies/ml within the past 7 months (28 weeks)
- •CD4 cell count ≥ 450 cells/μl on at least 2 occasions during the past 6 months
- •Informed consent
排除标准
- •Any significant medical illness in the past 12 weeks
- •Any evidence of AIDS-defining opportunistic infection
- •Current or gastrointestinal disease that may impact absorption of the study drug
- •ALT or AST >3X upper limit of normal
- •Hemoglobin, white blood cell counts or platelets ≥ grade 2 by US NIH DAIDS grading system
- •History of diabetes or fasting glucose >126mg/dl
- •Documented hepatitis B infection as indicated by the presence of HBsAG
- •History of clinically significant cardiac disease or clinically significant EKG abnormalities
- •History of retinal disease
- •History of malignancy
- •Females who are pregnant or with a positive urine pregnancy test during screening or women of child bearing potential who are unwilling to use an acceptable method of contraception to avoid pregnancy for 4 weeks before, during the study and 4 weeks after the study
研究组 & 干预措施
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Vorinostat (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Hydroxychloroquine (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Maraviroc (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Tenofovir (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Emtricitabine (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Efavirenz (Drug)
ART + VHM
Group 1: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
Plus: 3 X 14-day cycles of vorinostat administered at weeks 0, 4 and 8; hydroxychloroquine and maraviroc prescribed at week 0 for a period of 10 weeks.
干预措施: Darunavir (Drug)
ART alone
Group 2: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and either an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
干预措施: Tenofovir (Drug)
ART alone
Group 2: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and either an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
干预措施: Emtricitabine (Drug)
ART alone
Group 2: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and either an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
干预措施: Efavirenz (Drug)
ART alone
Group 2: Combination Antiretroviral Therapy prescribed at week 0 for a period of 10 weeks. Likely consisting of two NRTI such as tenofovir and emtricitabine and either an NNRTI, such as efavirenz. For subjects on NNRTI therapy, a protease inhibitor, such as darunavir will be substituted for the NNRTI 2 weeks prior to treatment interruption.
干预措施: Darunavir (Drug)
结局指标
主要结局
Proportion of patients with HIV RNA < 50 copies/ml following ART interruption
时间窗: 24 weeks
次要结局
- To compare histone acetylation between the VHM + ART and ART only groups Expressed as mean fluorescence intensity(10 weeks)
- To compare adverse events both related and unrelated to the combination of hydroxychloroquine and maraviroc between arms graded according to NCI Common Terminology for Adverse Events(34 weeks)
- The occurrence and severity of acute retroviral syndrome between arms following treatment interruption using a combination of at least 3 clinical symptoms such as fever, lymphadenopathy and pharyngitis(34 weeks)
- To compare markers of HIV persistence measured as total, integrated and 2-LTR circles HIV DNA. Measured as DNA copies/1000000 cells(34 weeks)
- To compare the cell-associated unspliced HIV RNA in total CD4+ T cells between the VHM+ ART and ART only arms. Measured as copies unspliced RNA/1000000 18S(34 weeks)
- Time to HIV RNA rebound after treatment interruption between VHM +ART versus ART only arms defined as > 1000 HIV-1 RNA copies/ml on two consecutive plasma samples(24 weeks)
- To compare the cell-associated spliced HIV RNA in total CD4+ T cells between the VHM+ ART and ART only arms. Measured as copies multi-spliced RNA/1000000 cells(34 weeks)
研究者
Nitiya Chomchey
Prof.Praphan Phanuphak, MD, PhD
SEARCH Research Foundation