Safety, Tolerability, and Efficacy of Efavirenz (EFV) Intensification on HIV-1 Reservoir Reduction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Safety as Measured by Adverse Events
研究概览
简要总结
The goal of this clinical trial is to see if Efavirenz (EFV) intensification to a baseline combination antiretroviral regimen (cART) can help reduce the size of the latent reservoir in people living with HIV (PLWH). The main questions this study aims to address are:
- is the addition of EFV to a cART regimen safe and well tolerated?
- Is there a reduction in the blood and tissue HIV reservoir after intensification?
Researchers will compare each participants reservoir size prior to and post EFV intensification.
详细描述
To evaluate the safety and tolerability of efavirenz (EFV) intensification on the HIV-1 reservoir. Participants with well controlled HIV, specifically with a HIV viral load (VL) <500 for at least 48 weeks will be eligible. Prior to enrollment, we will prescreen individuals to ensure they do not have a polymorphism in cytochrome P450 (CYP450) which results in rapid metabolism of the study drug efavirenz. Leukapheresis and lymph node (LN) fine needle aspirates will be collected at baseline. Participants eligible to participate will begin taking Efavirenz in addition to their baseline combination antiretroviral therapy. Blood samples (120ml) will be collected twice at day 30 and day 90 for cell associated HIV RNA and HIV DNA assessments. Follow-up LN aspirates and follow-up Leukapheresis will be collected at completion of study, between day 150-180, based on scheduling. At day 90 pharmacokinetic (PK) evaluation of EFV will take place to ensure therapeutic levels of Efavirenz. At the completion of the 180 day course of efavirenz, participants will stop efavirenz but continue their baseline HIV regimen. Cluster of Differentiation 4 (CD4), HIV viral load (VL) and monitoring chemistries will be performed at visits on day 30, day 90 and day 150-180.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age
- •Diagnosis of HIV
- •Documentation of at least two historical HIV-1 RNA viral load measurements <500 copies/mL while on ART obtained by standard assay.
- •No known non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations.
- •Currently on a stable regimen including an integrase strand transfer inhibitor (INSTI) and two nucleoside reverse transcriptase inhibitors (NRTI). Receiving the current regimen for at least 90 days prior to study entry with no intention to change for the duration of the study.
排除标准
- •Untreated depression, defined as a Patient health questionnaire 9 (PHQ-9) score > 15 at time of enrollment
- •Known prior NNRTI resistance, or INSTI resistance.
- •Cytochrome 450 polymorphism resulting in rapid or delayed metabolism of Efavirenz
- •Not currently on a PI based regimen.
- •Does not have an immunocompromising medical condition. (ie malignancies particularly leukemia, lymphoma, use of immunosuppressive or antineoplastic drugs or X-ray treatment).
- •Chronic, acute, or recurrent infections that are current and serious, in the opinion of the site investigator.
- •Breastfeeding patients as well as those whom are pregnant or plan to become pregnant during period of the study.
- •Those with active Hepatitis C or Hepatitis B.
研究组 & 干预措施
Efavirenz intensification
There is only one arm in this study
干预措施: Efavirenz 600mg (Drug)
结局指标
主要结局
Safety as Measured by Adverse Events
时间窗: From time of enrollment until completion of study on average 5 months
Safety as measured by number of serious adverse events, adverse events leading to study discontinuation or adverse events considered clinically significant
Size of the Latent Reservoir (Cluster of Differentiation 4 (CD4) Cells With Intact Provirus/Million CD4 T Cells)
时间窗: (1) at study enrolment and (2) 4 months post EFV intensification
Size of intact provirus pre and post Efavirenz intensification as measured by IPDA. (CD4 cells with intact provirus/million CD4T cells) Time frame: IPDA (CD4 T cells carrying intact HIV provirus per million total CD4 T cells) at least of two time points (1) at study enrolment and (2) 4 months post EFV intensification
Safety of Efavirenz intensification on a baseline cART regimen
时间窗: 3 months post completion of trial
Safety of Efavirenz intensification on a baseline cART regimen The safety will be addressed both with laboratory tests (CBC, CMP, CD4, HIV VL) performed monthly, and PHQ9 surveys (for the rare reported adverse effect of worsening depression with Efavirenz) in addition to asking patients more subjective questions of how they are feeling and tolerating the medications and self reporting of (rash, pruritis, mood changes, nausea, vomiting or new abnormal symptoms).
次要结局
- Size of the latent reservoir(within 2 years post study completion)
研究者
Rachel Presti
Associate Professor
Washington University School of Medicine