PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Fraction of patients with viral load suppression <400 copies/ml
研究概览
简要总结
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Tuberculosis (TB) treatment with rifampicin at the time of enrolment.
- •Co-infection with HIV-
- •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.
研究组 & 干预措施
NNRTI
干预措施: Efavirenz or Nevirapine (Drug)
Protease inhibitor
干预措施: Ritonavir-boosted lopinavir (Drug)
结局指标
主要结局
Fraction of patients with viral load suppression <400 copies/ml
时间窗: 12 months after enrolment
次要结局
- Weight(Within 12 months)
- Plasma cytokine levels(Within 12 months)
- Fraction of patients with viral load suppression <50 copies/ml(12 months after enrolment)
- Increment of CD4+ cell count of at least 100 cells/µL(12 months after enrolment)
- Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml(12 months after enrolment)
- Compliance.(Within 12 months)
- Frequency of adverse events and severe adverse events(Within 12 months)
- Death.(Within 12 months)
- Incidence of tuberculosis.(Within 12 months)