A Phase IIIB, Randomized Trial of Open-Label Efavirenz or Atazanavir With Ritonavir in Combination With Double-Blind Comparison of Emtricitabine/Tenofovir or Abacavir/Lamivudine in Antiretroviral-Naive Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,864
- 试验地点
- 52
- 主要终点
- Time From Randomization to Virologic Failure
研究概览
简要总结
Currently, the preferred anti-HIV regimens used in the United States consist of two nucleoside reverse transcriptase inhibitors (NRTIs) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV). However, with new anti-HIV drugs being approved, alternative regimens need to be tested to determine if new drug combinations have increased effectiveness in treating HIV. The purpose of this study is to test the safety, tolerability, and effectiveness of four different regimens in HIV-infected adults who have never taken anti-HIV drugs.
详细描述
Antiretroviral (ARV) treatment regimens consisting of EFV and two NRTIs are the most commonly prescribed regimens for the initial therapy of HIV-infected people in the United States. Such regimens are popular because the drugs are easy to administer, have overall excellent efficacy, and are well tolerated. However, because of concerns about long-term drug toxicity, the development of drug resistance, and potential complications in pregnant women, it is imperative that other drug combinations be investigated as possible alternative initial regimens. Drugs recently approved by the Food and Drug Administration (FDA) for HIV treatment include the protease inhibitor (PI) atazanavir (ATV) and the two NRTI coformulations emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and abacavir/lamivudine (ABC/3TC). Data are limited on the efficacy of these new drugs when part of anti-HIV drug regimens. This study will evaluate and compare the safety, tolerability, and efficacy of four different treatment regimens in HIV-infected treatment-naive adults.
The treatment portion of this study will last 96 weeks after the last participant is enrolled. Participants will be randomly assigned to one of four arms:
- Arm 1 participants will receive EFV, FTC/TDF, and placebo for ABC/3TC.
- Arm 2 participants will receive EFV, ABC/3TC, and placebo for FTC/TDF.
- Arm 3 participants will receive ritonavir (RTV)-boosted ATV, FTC/TDF, and placebo for ABC/3TC.
- Arm 4 participants will receive RTV-boosted ATV, ABC/3TC and placebo for FTC/TDF.
NOTE: Lopinavir/ritonavir may be used in substitution of other drugs for certain participants.
Study visits will occur at study entry; Weeks 1, 2, 4, 8, 16, and 24; and every 12 weeks thereafter. A physical exam, blood collection, and urine collection will occur at most visits. Two pharmacokinetic blood samples will be collected from participants between Weeks 4 and 24. Participants will undergo adherence training at study entry and will be asked to complete adherence questionnaires at selected study visits. Some participants will be asked to participate in ACTG A5224s, a metabolic substudy of ACTG A5202.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected. A resistance assay must be obtained if the participant has evidence of recent infection. More information on this criterion can be found in the protocol.
- •Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to study entry. Participants who have received ARVs as part of postexposure prophylaxis or who have received an investigational drug that was not an NRTI, NNRTI, or PI are eligible for this study.
- •HIV viral load greater than 1,000 copies/ml within 90 days prior to study entry
- •Certain laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the protocol
- •Willing to use acceptable forms of contraception
- •Parent or guardian able and willing to provide written informed consent, if applicable
- •Hepatitis B surface antigen (HBsAg) negative at study entry
排除标准
- •Immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Individuals receiving either stable physiologic glucocorticoid doses, corticosteroids for acute therapy for pneumocystis pneumonia, or a short course (2 weeks or less) of pharmacologic glucocorticoid therapy will not be excluded.
- •Known allergy/sensitivity to study drugs or their formulations
- •Active alcohol or drug use that, in the opinion of the investigator, would interfere with adherence to study requirements
- •Serious illness requiring systemic treatment or hospitalization. Patients who have completed therapy or are clinically stable on therapy for at least 7 days prior to study entry are not excluded.
- •Known clinically relevant cardiac conduction system disease
- •Requirement for any current medications that are prohibited with any study treatment.
- •Evidence of any major drug resistance-associated mutation on any genotype or evidence of significant resistance on any phenotype performed at any time prior to study entry.
- •Current imprisonment or involuntary incarceration for psychiatric or physical (e.g., infectious disease) illness
- •Breastfeeding. Women who become pregnant during the study will be unblinded and required to permanently discontinue their study regimens.
研究组 & 干预措施
EFV, FTC/TDF, and placebo ABC/3TC
Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Efavirenz (Drug)
EFV, FTC/TDF, and placebo ABC/3TC
Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Emtricitabine/Tenofovir disoproxil fumarate (Drug)
EFV, FTC/TDF, and placebo ABC/3TC
Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Abacavir/Lamivudine placebo (Drug)
EFV, ABC/3TC and placebo FTC/TDF
Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Abacavir/Lamivudine (Drug)
EFV, ABC/3TC and placebo FTC/TDF
Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Efavirenz (Drug)
EFV, ABC/3TC and placebo FTC/TDF
Participants will receive EFV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Emtricitabine/Tenofovir disoproxil fumarate placebo (Drug)
RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC
Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Atazanavir (Drug)
RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC
Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Emtricitabine/Tenofovir disoproxil fumarate (Drug)
RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC
Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Ritonavir (Drug)
RTV-boosted ATV, FTC/TDF, and placebo ABC/3TC
Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
干预措施: Abacavir/Lamivudine placebo (Drug)
RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF
Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Abacavir/Lamivudine (Drug)
RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF
Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Atazanavir (Drug)
RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF
Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Ritonavir (Drug)
RTV-boosted ATV, ABC/3TC, and placebo FTC/TDF
Participants will receive RTV-boosted ATV, ABC/3TC, and placebo for FTC/TDF for at least 96 weeks
干预措施: Emtricitabine/Tenofovir disoproxil fumarate placebo (Drug)
结局指标
主要结局
Time From Randomization to Virologic Failure
时间窗: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Blood samples for determining virologic failure were obtained at visit weeks 16 and 24 , and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level \>= 1000 copies/mL at or after 16 weeks after randomization and before 24 weeks, or \>=200 copies/mL at or after 24 weeks. The 5th percentile for time to virologic failure is the time (in weeks) at which 5% of the participants have experienced virologic failure.
Time From Treatment Dispensation to a Grade 3/4 Safety Event
时间窗: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks.
Grade 3/4 safety event is defined as a grade 3 or 4 sign, symptom, or laboratory abnormality that is at least one grade higher than at baseline, total bilirubin and creatine kinase (CPK) were excluded. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Time From Treatment Dispensation to Treatment Modification
时间窗: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details
Treatment modification is defined as the 1st modification of the regimen, including a permanent discontinuation, switch, or substitution.
次要结局
- Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification)(Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details)
- The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL(At Weeks 48 and 96)
- Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL(At Weeks 48 and 96)
- Change in CD4 Count (Cells/mm3) From Baseline(At Weeks 48 and 96)
- Number of Participants With Virologic Failure and Emergence of Major Resistance(Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details)
- Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.(Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details)
- Change in Fasting Total Cholesterol Level From Baseline(At Weeks 48 and 96)
- Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline(At Weeks 48 and 96)
- Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline(At Weeks 48 and 96)
- Change in Fasting Triglyceride Level From Baseline(At Weeks 48 and 96)