Nevirapine vs Ritonavir-boosted Lopinavir in ART Naive HIV-infected Adults in a Resource Limited Setting

Phase 4

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: ritonavir-boosted Lopinavir; Drug: nevirapine; Drug: Tenofovir/emtricitabine; Drug: Zidovudine/lamivudine

• Registration Number: NCT01772940
• Lead Sponsor: Centre Hospitalier Universitaire Saint Pierre

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12
• Primary Completion: 2011-10
• Study Completion: 2011-12
• Study First Submitted: 2013-01-14
• Study First Submitted QC: 2013-01-17
• Study First Posted: 2013-01-21
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-22
• Last Update Posted: 2013-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 425

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
nevirapine and tenofovir/emtricitabine	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
lopinavir/r and tenofovir/emtricitabine	ritonavir-boosted Lopinavir	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
lopinavir/r and tenofovir/emtricitabine	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
Nevirapine and zidovudine/lamivudine	Zidovudine/lamivudine	nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks
Lopinavir/r and zidovudine/lamivudine	ritonavir-boosted Lopinavir	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
Lopinavir/r and zidovudine/lamivudine	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
nevirapine and tenofovir/emtricitabine	nevirapine	nevirapine 200 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks
Nevirapine and zidovudine/lamivudine	nevirapine	nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks

Primary Outcome Measures

Name	Time	Method
Incidence of therapeutic failure	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 Outcome Measures

Name	Time	Method
HIV-1 RNA viral load less than 50 copies/ml	Through week 96	The percentage of patients with HIV-1 RNA \< 50 copies/ml
Immunologic response	Through week 96	Cluster of differentiation 4 (CD4) cell count change from baseline
HIV-1 resistance mutations	At baseline and at the time of virologic failure
Safety and tolerability	Through week 96	Incidence of adverse events and laboratory abnormalities
Changes in laboratory parameters	Through week 96

Trial Locations

Locations (1)

Cliniques Universitaires de Lubumbashi; 🇨🇬 Lubumbashi, Katanga, Congo