A Randomised, Double-blind, Placebo-controlled, Trial to Compare the Safety and Efficacy of Reduced Dose Versus Standard Dose EFV Plus Two Nucleotides (N(t)RTI) in Antiretroviral-naïve HIV-infected Adults Over 96 Weeks
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Kirby Institute
- Enrollment
- 636
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation
Study Overview
Brief Summary
Clinical data suggests that the standard dose of the anti-HIV medication, efavirenz (EFV), could be reduced without compromising its effectiveness. Lower drug doses could have fewer side effects and would make EFV more affordable. The purpose of this study is to compare the safety and effectiveness, over 96 weeks, of standard (600mg) versus reduced dose (400mg) EFV in controlling HIV as part of initial combination antiretroviral therapy.
Detailed Description
In this international, multicenter trial, 630 HIV infected patients who have not received any previous treatment for their HIV-infection will be enrolled. Participants will be randomized equally (1:1) to receive Truvada (tenofovir and emtricitabine) with either the standard or reduced dose of EFV. Neither the study doctor nor the participant will know which treatment the participant is receiving. Physical examinations, laboratory analyses and questionnaires will be performed at the 11 study visits at screening, baseline (Week 0), Weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. The primary aim of this study is to compare between treatment groups the proportion of patients with undetectable HIV viral load (HIV RNA < 200 copies/mL) after 48 weeks. Information on immune function, drug adherence, resistance to antiretrovirals, quality of life, mental state and HIV-related conditions will also be collected. Blood samples will be collected for future testing. Interim analyses will be performed when the first 125 participants in each treatment group reach week 24 and when all participants reach week 24. These interim analyses will provide an early check that the reduced dose of EFV suppresses HIV infection as effectively as the standard dose of EFV. A follow-up analysis will be performed when all participants reach week 96.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •HIV-1 positive by licensed diagnostic test
- •aged >16 years of age (or minimum age as determined by local regulations or as legal requirements dictate)
- •50 < cluster of differentiation (CD)4 <500 cells/µL
- •No prior AIDS-defining illness, using the Center for Diseases Control 1993 Case Definition (except pulmonary tuberculosis)
- •HIV RNA ≥1000 copies/mL
- •no prior exposure to antiretroviral therapy (ART) (including short course ART for preventing MTCT)
- •calculated creatinine clearance (CLCr) more than or equal to 50 mL/min (Cockcroft-Gault formula)
- •provision of written informed consent.
Exclusion Criteria
- •the following laboratory values:
- •absolute neutrophil count (ANC) <500 cells/μL
- •hemoglobin <7.0 g/dL
- •platelet count <50,000 cells/μL
- •alanine aminotransferase and/or aspartate aminotransferase >5 x upper limit of normal
- •pregnant women or nursing mothers
- •active opportunistic or malignant disease not under adequate control
- •use of immunomodulators within 30 days prior to screening
- •use of any prohibited medications
- •current alcohol or illicit substance use that might adversely affect study participation
Arms & Interventions
600 milligram (mg) Efavirenz
Eligible patients will be centrally randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
Intervention: Efavirenz 600mg (Drug)
400mg Efavirenz
Eligible patients will be centrally randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
Intervention: Efavirenz 400mg (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Plasma HIV-1 RNA <200 Copies/mL 48 Weeks After Randomisation
Time Frame: 48 weeks
Percentage of participants in each of the treatment arms with centrally quantified plasma HIV-1 RNA viral load \<200 copies/mL 48 weeks after randomisation.
Secondary Outcomes
- Percentage of Participants With Plasma HIV-1 RNA <400 Copies/mL and <50 Copies/mL at 48 and 96 Weeks After Randomisation(Baseline and 2 years)
- Mean Change From Baseline in CD4+ T-cell Count(Baseline and 2 years)
- Clinical Endpoints: Opportunistic Disease or Death, and Serious Non-AIDS-defining Events and Non-AIDS-related Mortality(up to 2 years)
- Change From Baseline in Metabolic Endpoints(Baseline and 2 years)
- Change From Baseline in Fasted Insulin Levels(Baseline and 2 years)
- Change in Selected Serum Biochemical Parameters(Baseline and 2 years)
- Change From Baseline in Estimate Creatinine Clearance(Baseline and 2 years)
- Steady-state Efavirenz Concentrations(Week 4)
- Adherence: Median Scores of Self-reported Adherence to Randomised Study Medications(2 years)