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

Study Overview
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Brief Summary
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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.

Official Title
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Nevirapine vs Ritonavir-boosted Lopinavir in ART HIV-infected Adults in a Resource-limited Setting; a Randomized, Multicenter, Parallel Group Study

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: nevirapine
* Drug: ritonavir-boosted Lopinavir
* Drug: Tenofovir/emtricitabine
* Drug: Zidovudine/lamivudine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nevirapine and tenofovir/emtricitabine<br>nevirapine 200 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks | Drug: nevirapine<br>* Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks<br>* Other names: Viramune;Drug: Tenofovir/emtricitabine<br>* tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks<br>* Other names: Truvada;|
| Experimental: lopinavir/r and tenofovir/emtricitabine<br>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 | Drug: ritonavir-boosted Lopinavir<br>* ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks<br>* Other names: Aluvia;Drug: Tenofovir/emtricitabine<br>* tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks<br>* Other names: Truvada;|
| Active Comparator: Nevirapine and zidovudine/lamivudine<br>nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks | Drug: nevirapine<br>* Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks<br>* Other names: Viramune;Drug: Zidovudine/lamivudine<br>* zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks<br>* Other names: Zidolam,combivir;|
| Experimental: Lopinavir/r and zidovudine/lamivudine<br>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 | Drug: ritonavir-boosted Lopinavir<br>* ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks<br>* Other names: Aluvia;Drug: Zidovudine/lamivudine<br>* zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks<br>* Other names: Zidolam,combivir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of therapeutic failure | 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 | At week 48 with follow-up until week 96 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First-line therapy, Protease inhibitor, Non-Nucleoside Reverse transcriptase Inhibitor, Resource-limited setting