An Open-label Study Evaluating the Resistance Profile of Single Dose Nevirapine(NVP) When Combined With a 4 or 7 Day Course of Combivir® (ZDV/3TC) Compared to Single Dose Nevirapine for the Prevention of Mother to Child Transmission (pMTCT) of HIV - Treatment Options Preservation Study (T.O.P.S.)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 407
- 试验地点
- 6
- 主要终点
- Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing
研究概览
简要总结
To determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir®, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
详细描述
An open-label, randomised, multicentre study to determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.
An interim analysis of the first 61 patients showed that a clinical and statistical difference exists between the occurrence of HIV-1 NNRTI resistant mutations in the single dose nevirapine only arm (50%) and the two other combination arms (9%). These findings partially answered the objectives outlined in the initial objectives. Consequently enrolment onto the single dose nevirapine arm was terminated. The objective of the trial was modified to compare whether either the 4 or the 7 day combination of ZDV+3TC and nevirapine would result in any significant reduction in the incidence of nevirapine resistance.
Study Hypothesis:
Evaluations of HIV-1 resistance patterns in trials of pMTCT have demonstrated nevirapine resistant HIV-1 isolates in approximately 15-20% of mothers 4-6 weeks after receiving either a single or two dose 200mg nevirapine regimen. Although the ability to detect these genotypic mutations decreases to 0% by about 18 months, it is not clear whether this resistance is clinically significant.(HIVNET 012).
Empirically then it would seem useful to develop a strategy to diminish the emergence of this early resistance, therefore this study is proposed to evaluate whether the effect of 4 or 7 days of 3TC+ ZDV added to a single dose nevirapine regimen for the prevention of MTCT will prevent the emergence of resistance to nevirapine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pregnant women identified at antenatal clinics after from 34 weeks gestation and who are antiretroviral drug naive.
- •Mothers with a documented positive HIV Rapid test confirmed by a detectable HI V-1 RNA PCR (viral load).
- •Mother to have a screening viral load of > 2000 RNA copies/mL.
排除标准
- •Mothers who, in the opinion of the investigator ,cannot be relied on to return with their infants for postnatal visits.
- •Mothers who have received any antiretroviral drugs previously.
- •Clinical suspicion of intra-uterine foetal death
- •Unwillingness or inability to reasonably comply with the protocol requirements.
- •Use of any other investigational product during the pregnancy and for the dura tion of the study period.
- •Patients with a recent history of pancreatitis or peripheral neuropathy.
- •Patients with renal failure requiring dialysis.
- •Patients with evidence of hepatic dysfunction as measured by total bilirubin > 2.5 times ULN or AST/ALT > 5 times ULN at the screening visit.
- •Patients with any one of the following additional laboratory abnormalities at screening : Haemoglobin concentration < 7.5 g/dl. Neutrophil count < 750 cells/mm
- •Platelet count < 75,000 cells/mm
- •Serum amylase > 2 x ULN.
- •recent history ( during the pregnancy) of drug abuse or alcoholism.
- •Mothers who will undergo elective caesarean section.
- •If known prior to delivery, mothers with foetuses with anomalies incompatible with life.
结局指标
主要结局
Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing
时间窗: 6 weeks following delivery
次要结局
未报告次要终点