The ARDENT Study: Atazanavir, Raltegravir, or Darunavir With Emtricitabine/Tenofovir for Naive Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,814
- 试验地点
- 57
- 主要终点
- Cumulative Probability of First Virologic Failure by Week 96
研究概览
简要总结
The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV infected patients who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen may not be an option for everyone, hence alternative regimens are needed.
This study was designed to look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. This study also examined drug tolerability and safety for the various drug combinations.
详细描述
Of the five anti-HIV drug classes, four were recommended as first-line regimens for patients who have never received anti-HIV treatment before (treatment naive): nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), Integrase Inhibitors (INIs) and protease inhibitors (PIs). The U.S. Department of Health and Human Services (HHS) guidelines recommend that treatment-naive HIV infected patients be treated with a triple drug regimen that includes 2 NRTIs + 1 NNRTI, 2 NRTIs + INI, or 2 NRTIs + 1 PI as their initial treatment regimen.
According to data, an efavirenz (EFV)-containing regimen (2 NRTIs + 1 NNRTI, with EFVas the NNRTI) requires fewer pills for the patient, has mild and few side effects, and is more effective in reducing viral load than other regimens, making it the preferred choice for most patients. However, for some patients, an EFV-containing regimen is not feasible due to side effects, acquired NNRTI-resistant HIV virus, or other undesirable effects. For these patients, it is necessary to find alternative regimens with comparable safety and efficacy. This study examined how well different combinations of anti-HIV drugs work, including safety and drug tolerability for various combinations.
This was a phase III, prospective, randomized study. Participants was randomly assigned to one of three different groups (treatment arms)-A, B, or C -each representing a different drug combination regimen, none of which contained an NNRTI.
Arm A: Atazanavir (ATV) + Ritonavir (RTV) + Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Arm B: Raltegravir (RAL) + FTC/TDF
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
- •HIV-1 infected
- •No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.
- •No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.
- •Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry
- •Certain laboratory values obtained within 60 days prior to study entry
- •Ability to obtain RTV by prescription
- •Completed cardiovascular risk assessment. More information on this criterion can be found in the study protocol.
- •Must agree to use acceptable forms of contraception while receiving study drugs and for 6 weeks after stopping the medications. More information on this criterion is available in the protocol.
- •Negative pregnancy test within 72 hours before initiating antiretroviral medication
- •Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites
- •Ability and willingness of subject or legal guardian/representative to give written informed consent
排除标准
- •Use of immunomodulators, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Those using stable physiologic glucocorticoid doses, a short course of pharmacologic glucocorticoid, corticosteroids for acute therapy treating an opportunistic infection, inhaled or topical corticosteroids, or granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) will not be excluded.
- •Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.
- •Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study
- •Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry
- •Requirement for any current medications that are prohibited with any study drugs
- •Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
- •Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected
- •Presence of decompensated cirrhosis
- •Pregnant or breastfeeding
研究组 & 干预措施
Arm A: ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Arm A: ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Ritonavir (Drug)
Arm A: ATV/RTV + FTC/TDF
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
干预措施: Atazanavir (Drug)
Arm B: RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Arm B: RAL + FTC/TDF
FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
干预措施: Raltegravir (Drug)
Arm C: DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Emtricitabine/tenofovir disoproxil fumarate (Drug)
Arm C: DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Darunavir (Drug)
Arm C: DRV/RTV + FTC/TDF
FTC/TDF, darunavir (DRV), and RTV, orally, once daily.
干预措施: Ritonavir (Drug)
结局指标
主要结局
Cumulative Probability of First Virologic Failure by Week 96
时间窗: From study entry to week 96
The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 96. Time to virologic failure was defined as the first time from study entry to the first of two consecutive HIV-1 RNA \>1000 copies/mL at or after week 16 and before week 24, or \>200 copies/mL at or after week 24. Week 16 is defined to occur between 14 (98 days) and 18 weeks (126 days) after study entry, week 24 is defined to occur between 22 (154 days) and 26 (182 days) after study entry, and week 96 is defined to occur between 88 (616 days) and 104 (728 days) after study entry.
Cumulative Incidence of Discontinuation of the RAL or PI Component of Randomized Treatment for Toxicity by Week 96
时间窗: From study entry to week 96
The cumulative incidence of discontinuation for toxicity by week 96 was estimated using competing risks with treatment discontinuation for other reasons considered as a competing event; participants completing the study on the RAL or PI component of their randomized regimen were considered censored at the earliest of the date of last patient contact and off study date.
次要结局
- Cumulative Incidence of First Adverse Event by Week 96(From study entry to week 96)
- Cumulative Probability of Time to Loss of Virologic Response (TLOVR) by Week 96(From study entry to week 96)
- Presence of Mutations Associated With NRTI Resistance(At the virologic failure at any time throughout the study (up to 213 weeks))
- Presence of Mutations Associated With ATV/RTV or DRV/RTV Resistance(At the virologic failure at any time throughout the study (up to 213 weeks))
- Presence of Mutations Associated With INI Resistance(At the virologic failure at any time throughout the study (up to 213 weeks))
- CD4+ T-cell Count(At Weeks 24, 48, 96, and 144)
- CD4+ T-cell Count Changes From Baseline(Study entry to weeks 24, 48, 96, and 144)
- Incidence of Death or AIDS Defining Events (CDC Category C)(Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable)
- Incidence of Targeted Serious Non-AIDS Defining Events (Renal Failure, Liver Disease, Serious Metabolic Disorder, and CVD)(Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable)
- Change in Fasting Total Cholesterol Level From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Fasting HDL Cholesterol Level From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Fasting Triglycerides Level From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Fasting Plasma Glucose Level From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Framingham 10-year Risk of MI or Coronary Death From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Waist Circumference From Baseline(Study entry to weeks 48, 96, and 144)
- Change in Waist:Height Ratio From Baseline(Study entry to weeks 48, 96, and 144)
- Self-reported Adherence(At Weeks 4, 24, 48, 96, and 144)