A Study to Evaluate Dolutegravir Plus Lamivudine Dual Therapy for the Treatment of Naïve HIV-1-infected Participants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 122
- 试验地点
- 26
- 主要终点
- Virologic Status at Week 24
研究概览
简要总结
This study was done to see if the combination of two anti-HIV medicines, dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir) taken once a day, provide a safe, effective, and well-tolerated treatment for HIV. DTG is a type of HIV medicine called an integrase inhibitor; 3TC is a type of HIV medicine called a reverse transcriptase inhibitor. DTG works by blocking integrase and 3TC works by blocking reverse transcriptase, two HIV proteins (enzymes). This prevents HIV from multiplying and lowers the viral load (amount of HIV in the blood). Both DTG and 3TC are currently part of Food and Drug Administration (FDA) recommended regimens along with a third active drug. Since some HIV medicines have side effects and are costly, there is interest in whether HIV can be successfully controlled with fewer than three HIV drugs.
详细描述
This study was a phase II, single-arm, open-label pilot study designed to estimate the efficacy of dolutegravir (DTG) plus lamivudine (3TC) as initial combination ART (antiretroviral therapy) in HIV-1 infected treatment naive participants. The target enrollment was 120 participants with a cap of N=90 participants with screening HIV-1 RNA <= 100,000 copies/mL. The study aimed to enroll >= 20% women. The expected follow-up for each participant was 52 weeks.
Visits occurred at screening, entry, and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 from study entry. All signs/symptoms within 30 days prior to entry were recorded. Subsequently, grade 2 or higher rash and all other grade 3 or higher signs and symptoms were recorded. All participants underwent routine monitoring including plasma HIV-1 RNA levels, CD4+ cell count, hematology, chemistry, urinalysis, and pregnancy testing (for women of reproductive potential).
Population-based protease (PR), reverse transcriptase (RT) and integrase genotyping were done at the time of confirmed virologic failure. Plasma samples were stored for potential future studies to assess the impact of adherence, drug-resistant minority viral variants, and DTG exposure on virologic and CD4+ cell count responses to DTG plus 3TC. All participants also underwent UGT1A1 genotyping.
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 infection.
- •Plasma HIV-1 RNA ≥1000 copies/mL and <500,000 copies/mL obtained within 90 days prior to study entry.
- •No evidence of any RT, any integrase, or major protease resistance mutation (according to the 2014 IAS-USA drug resistance mutations list, available at https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) based on pre-ARV (antiretroviral) treatment genotype performed any time prior to study entry.
- •ARV treatment drug-naive (defined as no previous ARV treatment at any time prior to study entry, with the exception of successful post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP).
- •The following laboratory values obtained within 45 days prior to study entry:
- •ANC (absolute neutrophil count) ≥750/mm^3
- •Hemoglobin ≥10.0 g/dL
- •Platelets ≥ 50,000/mm^3
- •Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-Gault equation
- •AST (aspartate aminotransferase) <5 x ULN (upper limit of normal)
- •ALT (alanine aminotransferase) <5x ULN
- •Total bilirubin <1.5 x ULN
- •Hepatitis B surface antigen negative within 45 days prior to study entry.
- •For women with reproductive potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry.
- •If participating in sexual activity that could lead to pregnancy, female participants with reproductive potential must have agreed to use one form of contraceptive as listed in the protocol while receiving protocol-specified medications and for 30 days after stopping the medications.
- •Ability and willingness of participant or legal representative to provide informed consent.
排除标准
- •Serious illness requiring systemic treatment and/or hospitalization.
- •Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy.
- •Pregnancy or breastfeeding.
- •Receipt of systemic cytotoxic chemotherapy or dofetilide.
- •Known allergy/sensitivity to any of the study drugs or their formulations.
- •Active drug or alcohol use or dependence that may interfere with adherence to study requirements, in the opinion of the site investigator.
- •Active hepatitis C virus (HCV) treatment or anticipated need for treatment within study period.
- •Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Severe hepatic impairment (Class C) as determined by Child-Pugh classification.
研究组 & 干预措施
Arm 1: DTG 50 mg + 3TC 300 mg
Dolutegravir 50mg and Lamivudine 300mg, orally daily
干预措施: Dolutegravir (Drug)
Arm 1: DTG 50 mg + 3TC 300 mg
Dolutegravir 50mg and Lamivudine 300mg, orally daily
干预措施: Lamivudine (Drug)
结局指标
主要结局
Virologic Status at Week 24
时间窗: At 24 weeks after study entry
Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 24 Window are provided below. Virologic success is defined as HIV-1 RNA \<50 copies/mL and on study treatment (FDA Snapshot definition).
次要结局
- Virologic Status at Week 12(At 12 weeks after study entry)
- Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL- As Treated(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- As Treated(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Creatinine Clearance(Baseline, weeks 4, 12, 24, 32, 40 and 48)
- Number of Participants With Grade 3 of Higher Adverse Events(from study treatment dispensation through up to week 52 or until study discontinuation)
- Virologic Status at Week 48(At 48 weeks after study entry)
- CD4+ Cell Count(Baseline, weeks 4, 12, 24, and 48)
- Change in CD4+ Cell Count(Baseline, weeks 4, 12, 24, and 48)
- Virologic Failure(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/mL - Missing = Failure(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Proportion of Participants With Plasma HIV-1 RNA < 200 Copies/mL - Missing = Failure(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL - Missing = Ignored(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- ITT Missing = Ignored(Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48)
- Fasting Lipids and Glucose(Baseline and week 48)
- Number of HIV-1 Drug Resistance Mutation Occurrences in Participants(at the time of virologic failure)