Nevirapine vs Ritonavir-boosted Lopinavir in ART HIV-infected Adults in a Resource-limited Setting; a Randomized, Multicenter, Parallel Group Study
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 425
- Locations
- 1
- Primary Endpoint
- Incidence of therapeutic failure
Study Overview
Brief Summary
In resource-limited setting, concerns remain regarding the emergence of virologic failure and high-level drug resistance mutations (DRM) during WHO recommended first-line antiretroviral therapy (ART) with non-nucleoside reverse transcriptase inhibitors (NNRTI) based regimens for Human immunodeficiency virus 1 (HIV1) infected patients. The study hypothesis is that a boosted-protease inhibitor regimen has a better outcome than a NNRTI-based regimen with a low genetic barrier to resistance.
The study is a randomized, multicenter, factorial trial (conducted in Congo), in treatment- naïve adults receiving for 96 weeks ritonavir- boosted lopinavir(LPV/r) or nevirapine (NVP) each in combination with tenofovir (TDF) /emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). The primary end point is the incidence of therapeutic (clinical and/or virologic)failure by study week 24.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Antiretroviral-therapy naïve HIV-1 infected Adults
- •WHO clinical stage 3 and CD4 <350/mm3 or
- •WHO clinical stage 4 or
- •CD4 cell count < 200/mm3
- •Negative pregnancy test
Exclusion Criteria
- •Hemoglobin < 8.5 g/dL (female) or 9.0 g/dL (male)
- •Estimated Glomerular Filtration Rate < 50 ml/ minute (Cockcroft-Gault equation)
- •Hepatic transaminases (AST and ALT)> 3 x upper limit of normal
- •Active tuberculosis
- •Pregnancy
- •Females who are breastfeeding
Arms & Interventions
nevirapine and tenofovir/emtricitabine
nevirapine 200 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks
Intervention: nevirapine (Drug)
nevirapine and tenofovir/emtricitabine
nevirapine 200 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks
Intervention: Tenofovir/emtricitabine (Drug)
lopinavir/r and tenofovir/emtricitabine
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks
Intervention: ritonavir-boosted Lopinavir (Drug)
lopinavir/r and tenofovir/emtricitabine
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks
Intervention: Tenofovir/emtricitabine (Drug)
Nevirapine and zidovudine/lamivudine
nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks
Intervention: nevirapine (Drug)
Nevirapine and zidovudine/lamivudine
nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks
Intervention: Zidovudine/lamivudine (Drug)
Lopinavir/r and zidovudine/lamivudine
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg once daily combined with zidovudine 300 mg/lamivudine 150 mg once daily, per os for 96 weeks
Intervention: ritonavir-boosted Lopinavir (Drug)
Lopinavir/r and zidovudine/lamivudine
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg once daily combined with zidovudine 300 mg/lamivudine 150 mg once daily, per os for 96 weeks
Intervention: Zidovudine/lamivudine (Drug)
Outcomes
Primary Outcomes
Incidence of therapeutic failure
Time Frame: At week 48 with follow-up until week 96
The primary end point is the proportion of patients with therapeutic failure defined as: * the occurence or relapse by week 24 of a World Health Organization (WHO) stage 4 or 3 event, or * death by week 24, or * discontinuation of study drugs due to toxicity at any time, or * virological failure defined as HIV-1 RNA \> 1000 copies/ml by week 24
Secondary Outcomes
- Changes in laboratory parameters(Through week 96)
- HIV-1 RNA viral load less than 50 copies/ml(Through week 96)
- Immunologic response(Through week 96)
- HIV-1 resistance mutations(At baseline and at the time of virologic failure)
- Safety and tolerability(Through week 96)
Investigators
Clumeck Nathan
Chief infectious diseases , Professor of Medicine
Centre Hospitalier Universitaire Saint Pierre