Randomized, Open-Label Evaluation of Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Persons From Resource-Limited Settings (PEARLS) Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,571
- 试验地点
- 42
- 主要终点
- Time to Treatment Failure (PI Comparison)
研究概览
简要总结
This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.
详细描述
In developed countries, standard effective antiretroviral (ARV) therapy for treatment-naive HIV infected people includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, direct comparisons of ARV efficacy in persons that more closely reflect the worldwide demographics of HIV-1 infection are needed.> > Trial participants were recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.>
> All participants were randomly assigned to one of three arms, and random allocation was stratified by 2 factors: country, and screening plasma HIV-1 RNA level (< 100,000 copies/mL versus >= 100,000 copies/mL). Participants assigned to the ZDV/3TC+EFV arm received lamivudine/zidovudine twice daily and efavirenz once daily. Participants assigned to the ddI+FTC+ATV arm received emtricitabine, atazanavir, and enteric-coated didanosine once daily. Participants assigned to the TDF/FTC+EFV arm received emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily. >
>
> Physical exam and blood collection occurred at entry and at most study visits. Participants experiencing virologic failure were offered a switch to another regimen. >
> On May 23, 2008, the ddI+FTC+ATV was closed following a planned interim review by the study's independent Data and Safety Monitoring Board (DSMB). The DSMB recommendation was based upon compelling evidence that this arm had significantly more virologic failure (and therefore was inferior when) compared to the ZDV/3TC+EFV arm . Participants still receiving ddI+FTC+ATV were offered alternative medications, and all participants continued to be followed. >
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
- 未提供
排除标准
- •More than 7 days exposure to ARVs (except for single-dose NVP or ZDV for any period for the purpose of pMTCT)>
- •Acute therapy for serious medical illnesses within 14 days prior to study entry>
- •Certain abnormal laboratory values>
- •Radiation therapy or chemotherapy within 45 days prior to study entry. >
- •Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry. >
- •Current alcohol or drug abuse that, in the opinion of the site investigator, would interfere with study participation>
- •Inflamed pancreas within 3 years prior to study entry>
- •Allergy/sensitivity to any of the study drugs or their formulations>
- •Heart rate less than 40 beats/min>
- •History of untreated, active second- or third-degree heart block>
- •Currently detained in jail or for treatment of a psychiatric or physical illness>
- •Vomiting or inability to swallow medications>
- •Pregnancy>
研究组 & 干预措施
ZDV/3TC+EFV
ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz
干预措施: Efavirenz (Drug)
ZDV/3TC+EFV
ZDV/3TC+EFV participants will receive lamivudine/zidovudine and efavirenz
干预措施: Lamivudine/Zidovudine (Drug)
ddI+FTC+ATV
ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine
干预措施: Atazanavir (Drug)
ddI+FTC+ATV
ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine
干预措施: Didanosine (enteric-coated) (Drug)
ddI+FTC+ATV
ddI+FTC+ATV participants will receive emtricitabine, atazanavir, and enteric-coated didanosine
干预措施: Emtricitabine (Drug)
TDF/FTC+EFV
TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz
干预措施: Efavirenz (Drug)
TDF/FTC+EFV
TDF/FTC+EFV participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz
干预措施: Emtricitabine/Tenofovir disoproxil fumarate (Drug)
结局指标
主要结局
Time to Treatment Failure (PI Comparison)
时间窗: Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up until ddI+FTC+ATV arm closed (May 22, 2008).
Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005), plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).
Time to Treatment Failure (NRTI Comparison)
时间窗: Virologic failure starting 14 weeks following randomization; disease progression starting 12 weeks following randomization; and death occurring at any time following randomization. Follow-up through study closure (May 31, 2010).
Time from randomization to the earliest of: scheduled week of first plasma sample meeting virologic failure (two consecutive plasma HIV-1 RNA values 1,000 copies/mL or higher, regardless of whether ARV medications being taken at the time); scheduled week of first AIDS defining diagnosis (WHO Stage 4 (2005) plus microsporidiosis, cyclospora gastroenteritis and Chaga's disease), not attributed to Immune Reconstitution Inflammatory Syndrome (reviewed by chairs); date of death (due to any cause). Plasma drawn every 8 weeks (except confirmation samples could be drawn earlier).
次要结局
- Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (PI Comparison)(Throughout follow-up until ddI+FTC+ATV arm closed (May 22,2008))
- Time to Immunologic Failure (PI Comparison)(At or after Week 48 (including only follow-up until ddI+FTV+ATV arm closed - May 22,2008))
- Change in CD4 Count From Screening to Weeks 24, 48, 96 (PI Comparison)(weeks 24, 48 and 96 (including follow-up until ddI+FTC+ARV arm closed - May 22, 2008))
- Time to First Dose Modification or Grade 3 or 4 Adverse Event (PI Comparison)(Throughout study follow-up until ddI+FTC+ATV arm closed (May 22, 2008))
- Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (PI Comparison)(At Weeks 24 and 48 (including only follow-up until ddI+FTC+ARV arm closed - May 22, 2008))
- Change in CD4 Count From Screening to Weeks 24, 48, 96 (NRTI Comparison)(weeks 24, 48 and 96 (including all follow-up through to study closure on May 31, 2010))
- Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(PI Comparison)(Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008))
- Time to Immunologic Failure (NRTI Comparison)(At or after Week 48 (including all follow-up through study closure - May 31,2010))
- Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)(Week 96 (using follow-up through to study closure on May 31,2010))
- Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)(Week 48 using follow-up through study closure on May 31,2010)
- Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(PI Comparison)(Week 48 (using follow-up only until closing of ddI+FTV+ATV arm on May 22,2008))
- Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml (NRTI Comparison)(At Weeks 24 and 48 (including follow-up through to study closure on May 31, 2010))
- Time to Loss of Virologic Response at Week 48 (Defined by FDA TLOVR Algorithm - Excluding Study Allowed ARV Substitutions)(NRTI Comparison)(Week 48 (using follow-up through study closure on May 31,2010))
- Time to Discontinuation of Initial Antiretroviral (ARV) Therapy (NRTI Comparison)(Throughout follow-up until study closed (May 31,2010))
- Time to First Dose Modification or Grade 3 or 4 Adverse Event (NRTI Comparison)(Throughout study follow-up until study closure (May 31, 2010))
- Time to Loss of Virologic Response at Week 96 (Defined by FDA TLOVR Algorithm - Including All ARV Substitutions)(NRTI Comparison)(Week 96 using follow-up through study closure on May 31,2010)