Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 89
- 试验地点
- 7
- 主要终点
- Proportion of Participants With Treatment Failure
研究概览
简要总结
HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24
详细描述
DESIGN HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24
All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count, hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual viremia.
DURATION 48 weeks
SAMPLE SIZE 90 subjects
POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir > 200 cells/mm3, no baseline resistance, no history of virologic failure, and HIV RNA <50 copies/mL for at least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug regimen
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 Infection
- •HIV-1 RNA <50 copies/mL on all measurements within 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug antiretroviral regimen. (A history of switching for simplification and/or tolerability is allowed. At least two measurements within the previous 48 weeks are required prior to study screening.)
- •No history of virologic failure, defined as consecutive HIV RNA > 50 copies/mL after 12 months of initiating ART. An isolated (non-consecutive) HIV RNA > 50 copies/mL (but less than 400 copies/mL) is permitted after 12 months of initiating ART but not in the 48-week window prior to study entry.
- •Screening plasma HIV RNA < 20 copies/mL using the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test V2.0, obtained within 45 days prior to study entry
- •Nadir CD4 count >200 cells/mm
- •Pretreatment genotype documenting no mutations in the protease or reverse transcriptase genes
- •No known resistance to integrase inhibitors
- •Laboratory values obtained within 45 days prior to study entry:
- •ANC >750 Hemoglobin >10 g/dL Platelets >50,000 Calculated creatinine clearance (CrCl) >50 mL/min
- •Negative serum or urine pregnancy test
- •Men and women age greater or equal to 18 years.
- •Ability to continue current regimen (i.e, have uninterrupted access)
- •No evidence of chronic hepatitis B
排除标准
- •Serious illness or AIDS-related complication within 21 days of screening requiring systemic treatment and/or hospitalization
- •Treatment within 30 days prior to study entry with immune modulators
- •Vaccination within 7 days
- •Active HCV treatment or anticipated need for treatment within study period. (HCV infection alone is not exclusionary)
- •Unstable liver disease or severe hepatic impairment
- •Known allergy or hypersensitivity to DTG or lamivudine.
- •Active drug or alcohol use or dependence that could interfere with adherence to study requirements
- •ALT (alanine aminotransferase) >5 x ULN (upper limit of normal) OR ALT >3 x ULN and total bilirubin >1.5 x ULN (with 35% direct bilirubin)
研究组 & 干预措施
dolutegravir plus lamivudine
dolutegravir 50 mg plus lamivudine 300 mg once daily
干预措施: dolutegravir (Drug)
dolutegravir plus lamivudine
dolutegravir 50 mg plus lamivudine 300 mg once daily
干预措施: lamivudine (Drug)
Continue current ART regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
干预措施: Continue current antiretroviral regimen (Drug)
结局指标
主要结局
Proportion of Participants With Treatment Failure
时间窗: 24 weeks
Proportion of participants with treatment failure (defined as virologic failure (HIV RNA \>50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen
次要结局
- Change in LDL Cholesterol From Baseline to Week 48(Baseline and Week 48)
- Drug Resistance Associated Mutations(48 weeks)
- Change in CD4 Count From Baseline to Week 48(Baseline and 48 weeks)
- Change in Total Cholesterol From Baseline to Week 48(Baseline and 48 weeks)
- Change in Creatinine Clearance From Baseline to Week 48(Baseline and Week 48)
- Proportion of Participants With Virologic Success(48 weeks)
研究者
Babafemi Taiwo
Professor
Northwestern University