PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial (PIONA)
PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
BACKGROUND: Since 1996 the combination of three or more drugs has been the mainstay of human immunodeficiency virus (HIV) treatment. The most important types of drugs are called nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) Response to treatment is measured as increasing CD4+ cell count and decreasing HIV viral load. A major problem is the development of resistance. NNRTIs are recommended as part of first-line treatment of HIV in Africa but many Africans have a slower NNRTI clearance than Caucasians making them more susceptible for development of resistance in case of treatment interruptions. PIs might therefore be a better option in an African setting with low adherence.
AIM: To evaluate two different treatment regimens in HIV-1 infected patients:
A) A NNRTI (efavirenz/nevirapine) based regimen and B) A PI (ritonavir-boosted lopinavir) based regimen with regard to treatment outcomes. HYPOTHESIS: Treatment with a PI will be superior to treatment with a NNRTI due to less development of resistance.
METHODS: Treatment-naïve adult HIV-1 patients enrolled in an existing cohort The West African Retrovirus and Acquired Immune Deficiency (WARAID) cohort in Guinea Bissau with CD4+ cell count ≤ 350 cells/µL and/or clinical signs of immune suppression (World Health Organization (WHO) clinical stage 3 or 4) will be randomised 1:1 to: Treatment A: 2 NRTIs (lamivudine and either zidovudine or stavudine) and 1 NNRTI (efavirenz or nevirapine) or Treatment B: 2 NRTIs (same as in treatment A) and 1 PI (ritonavir-boosted lopinavir). Primary outcome: Viral load suppression <400 copies/ml 12 months after enrolment.
PERSPECTIVES: Guidelines for treatment of HIV in Africa are more or less a copy of the guidelines used in Europe and North America. Genetic differences in pharmacokinetics, more women infected in Africa and difficulties ensuring good adherence mean that results obtained from Caucasian patients are not directly transferrable to African patients. The results of this study will hopefully help guiding the treatment of HIV in Africa in the future. The investigators believe the HIV infected people in West Africa deserve the same evidence-based medicine as in developed countries.
研究概览
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Bissau、几内亚比绍
- Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Antiretroviral treatment (ART) naïve HIV-1 infected patients. Women receiving ART during pregnancy can be included.
- Age ≥ 18 years
- CD4+ cell count ≤ 350 cells/µL and/or
- Clinical signs of immune suppression (WHO clinical stage 3 or 4) irrespective of CD4+ cell count.
Exclusion Criteria:
- Tuberculosis (TB) treatment with rifampicin at the time of enrolment.
- Co-infection with HIV-2.
- Grade 3 or 4 alanine transaminase (ALAT) elevation (>5 times upper normal limit).
- Patients with cerebral disturbances that complicates the ability to give informed consent or follow the treatment regime.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器：NNRTI
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2 NRTIs (lamivudine 150 mg "bis in die - twice a day" (BID) and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 NNRTI (efavirenz 600 mg "omne in die - once daily" (OD) or nevirapine 200 mg OD for the first 2 weeks and after that 200 mg BID).
Efavirenz will be used in all male patients according to national HIV guidelines.
Pregnant patients and female patients with a child bearing potential will be treated with nevirapine if CD4+ cell count is ≤ 350 cells/mm3 with close monitoring of liver enzymes during the first 12 weeks in patients with CD4+ cell count >250 cells/mm3.
Females beyond childbearing age will be treated with efavirenz.
其他名称：
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有源比较器：Protease inhibitor
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2 NRTIs (lamivudine 150 mg BID and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 PI (ritonavir-boosted lopinavir 400/100 mg BID).
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Fraction of patients with viral load suppression <400 copies/ml
大体时间：12 months after enrolment
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12 months after enrolment
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Fraction of patients with viral load suppression <50 copies/ml
大体时间：12 months after enrolment
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12 months after enrolment
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Increment of CD4+ cell count of at least 100 cells/µL
大体时间：12 months after enrolment
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12 months after enrolment
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Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
大体时间：12 months after enrolment
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12 months after enrolment
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Frequency of adverse events and severe adverse events
大体时间：Within 12 months
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Within 12 months
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Compliance.
大体时间：Within 12 months
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Compliance defined as the actual amount of medicine taken compared to the planned amount for the same treatment period.
A pill count is carried out at each visit.
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Within 12 months
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Incidence of tuberculosis.
大体时间：Within 12 months
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Within 12 months
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Death.
大体时间：Within 12 months
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Death at 12 month follow-up.
Any patient lost to follow-up will be attempted visited at home by a field assistant 1 month after latest visit due.
Information on patient death from family or neighbors will be recorded as a mortality event and a verbal autopsy conducted.
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Within 12 months
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Weight
大体时间：Within 12 months
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Increase in body mass index (BMI) and frequency of severe weight loss (>10% of presumed or measured body weight).
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Within 12 months
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Plasma cytokine levels
大体时间：Within 12 months
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Within 12 months
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合作者和调查者
合作者
调查人员
- 首席研究员：Sanne Jespersen, MD、Aarhus University Hospital Skejby
- 研究主任：Alex L Laursen, MD, DMSc、Aarhus University Hospital Skejby
- 研究主任：Lars Oestergaard, Prof MD DMSc、Aarhus University Hospital Skejby
- 学习椅：Christian Wejse, MD, PhD、Aarhus University Hospital Skejby
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 11/CNES/2010
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