Phase II, Parallel, Randomized, Clinical Trials Comparing the Responses to Initiation of NNRTI-Based Versus PI-Based Antiretroviral Therapy in HIV Infected Infants Who Have and Have Not Previously Received Single Dose Nevirapine for Prevention of Mother-to-Child HIV Transmission
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 452
- 试验地点
- 10
- 主要终点
- Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
研究概览
简要总结
A single dose of nevirapine (SD NVP) given to an HIV infected pregnant woman followed by a single dose to her infant has been shown to be an effective way of reducing the risk of mother-to-child transmission (MTCT) of HIV. The purpose of this study was to compare the effectiveness of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral regimen versus a protease inhibitor (PI)-based regimen in HIV infected infants who had or had not been exposed to SD NVP for prevention of MTCT.
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>> A five year follow up has been added to the study.
详细描述
Single dose nevirapine (SD NVP) has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are recommended for use by the World Health Organization (WHO) in resource-limited settings. However, research suggests that mothers and infants exposed to SD NVP experience higher virologic failure rates when treated with NNRTI-based regimens than their unexposed counterparts. Data show that the use of SD NVP is associated with NNRTI resistance in HIV infected women and infants. The purpose of this trial was to compare and evaluate virologic responses to an NNRTI-based regimen versus a protease-inhibitor (PI)-based regimen in HIV infected infants who had or had not been exposed to SD NVP intrapartum and after birth.
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>> Participants were enrolled into one of two Cohorts with proposed enrollment into each Cohort of 288 participants. Cohort I participants must have received SD NVP for prevention of MTCT. Cohort II participants and their mothers must not have previously received NVP or any other NNRTIs. Participants in both Cohorts were randomly assigned to receive either an NNRTI (Coh I:NVP and Coh II: NVP) or PI (Coh I: LPV/r and Coh II: LPV/r) -based regimen. The NNRTI-based regimen included NVP, zidovudine (ZDV) and lamivudine (3TC). The PI-based regimen included lopinavir/ritonavir (LPV/r), ZDV and 3TC. If participants experienced adverse reactions to ZDV, stavudine (d4T) could be substituted. Randomization was stratified by age (6-<12 months vs. >=12 months, with the 2-<6 month stratum added in protocol version 4.0 when the lower age limit was decreased from 6 months to 2 months).
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>> Study visits were scheduled at entry, weeks 2, 4, 8, 12, 16, 24 and then every 24 weeks. A physical exam, blood collection, and assessments of HIV-related symptoms occurred at all visits.
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
- 2 Months 至 36 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Coh I: NVP
Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
干预措施: Lamivudine (Drug)
Coh I: NVP
Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
干预措施: Nevirapine (Drug)
Coh I: NVP
Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
干预措施: Zidovudine (Drug)
Coh I: LPV/r
Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
干预措施: Lamivudine (Drug)
Coh I: LPV/r
Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
干预措施: Lopinavir/ritonavir (Drug)
Coh I: LPV/r
Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
干预措施: Zidovudine (Drug)
Coh II: NVP
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
干预措施: Lamivudine (Drug)
Coh II: NVP
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
干预措施: Nevirapine (Drug)
Coh II: NVP
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
干预措施: Zidovudine (Drug)
Coh II: LPV/r
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen
干预措施: Lamivudine (Drug)
Coh II: LPV/r
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen
干预措施: Lopinavir/ritonavir (Drug)
Coh II: LPV/r
Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen
干预措施: Zidovudine (Drug)
结局指标
主要结局
Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment
时间窗: Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010)
Treatment failure is defined as a confirmed plasma HIV-1 RNA level that is \<1 log10 copies/mL below the study entry value at 12 to 24 weeks after treatment is initiated OR a confirmed plasma HIV-1 RNA level \>400 copies/mL at 24 weeks OR permanent discontinuation of the randomized NNRTI or PI component of study treatment at or prior to 24 weeks of treatment for any reason including death. Results report percent of participants reaching a treatment failure endpoint by week 24 calculated using the Kaplan-Meier method.
次要结局
- Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment(Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks))
- Time From Randomization to Virologic Failure(Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks))
- Percent of Participants Experiencing Virologic Failure(Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010))
- Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment(On randomized NNRTI or PI component of study treatment and until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010))
- Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus(Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks))
- Time From Randomization to Death(Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks))
- Change in CD4 Percent From Entry to Week 48(48 weeks if before date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010))
- Time From Randomization to HIV-related Disease Progression or Death(Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks))