A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 113
- 试验地点
- 22
- 主要终点
- Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
研究概览
简要总结
The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.
详细描述
Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure at or prior to week 24 after initiating raltegravir (RAL) plus darunavir/ritonavir (DRV/RTV).
The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.
After entry, all participants will have scheduled visits at weeks 1, 4, 12, 24, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.
RAL and DRV were provided by the study. RTV was not provided by the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Plasma HIV-1 RNA of at least 5,000 copies/mL within 90 days prior to study entry
- •HIV genotype (for reverse transcriptase and protease) performed at any time prior to study entry. More information on this criterion can be found in the protocol.
- •ARV drug-naive. More information on this criterion can be found in the protocol.
- •Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry
- •Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.
排除标准
- •Serious illness requiring systemic treatment and/or hospitalization for at least 7 days prior to study. More information on this criterion can be found in the protocol.
- •Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone
- •Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
- •Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
- •Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
- •Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
- •Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion.
- •Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study.
- •Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
- •Pregnant or breastfeeding
研究组 & 干预措施
RAL + DRV/RTV
Raltegravir (400 mg BID) plus Darunavir/Ritonavir (800 mg/100 mg QD) for 52 weeks
干预措施: Raltegravir (Drug)
RAL + DRV/RTV
Raltegravir (400 mg BID) plus Darunavir/Ritonavir (800 mg/100 mg QD) for 52 weeks
干预措施: Darunavir/Ritonavir (Drug)
结局指标
主要结局
Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24
时间窗: From start of study treatment to week 24
Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA \>= 1000 copies/ml or confirmed rebound from the week 4 value by \>0.5 log10 copies/ml (for subjects with week 4 value \<= 50 copies/ml, confirmed rebound to \>50 copies/ml); at week 24 or later, confirmed value \> 50 copies/ml. Viral load confirmation was scheduled 7-35 days after initial virologic failure. The proportion was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.
次要结局
- Change in Plasma HIV-1 RNA From Baseline to Week 1(Baseline and week 1)
- Number of Participants With Protease Drug Resistance at Virologic Failure(From 12 weeks after starting study treatment to week 52)
- Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24(From start of study treatment through week 24)
- Change in Fasting Low-density Lipoprotein at Week 24(From start of study treatment through week 24)
- Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24(From start of study treatment to Week 24)
- Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24(From start of study treatment to week 24)
- Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48(From start of study treatment to week 48)
- Number of Participants With Pretreatment Drug Resistance(At screening)
- Number of Participants With Perfect Overall Adherence by Self Report(From one week after starting study treatment to week 52)
- Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment(From start of study treatment to week 52)
- Number of Participants With Integrase Drug Resistance at Virologic Failure(From 12 weeks after starting study treatment to week 52)
- Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48(From start of study treatment through week 48)
- Plasma Trough Concentration of Raltegravir(From start of study treatment to week 52)
- Plasma Trough Concentration of Darunavir(From start of study treatment to week 52)
- Change in Fasting Low-density Lipoprotein at Week 48(From start of study treatment through week 48)
- Change in CD4 Count at Week 48(From start of study treatment through week 48)