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

Centre Hospitalier Universitaire Saint Pierre

Status and phase: Completed; Phase 4

Conditions: HIV-1 Infection

Treatments: Drug: Tenofovir/emtricitabine; Drug: ritonavir-boosted Lopinavir; Drug: nevirapine; Drug: Zidovudine/lamivudine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01772940

Lubumbashi trial

Details and patient eligibility

About

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.

Enrollment: 425 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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425 participants in 4 patient groups

nevirapine and tenofovir/emtricitabine

Active Comparator group

Description:

nevirapine 200 mg twice daily combined with tenofovir 300 mg/emtricitabine 200 mg (fixed-dose combination) once daily, per os for 96 weeks

Treatment:

Drug: nevirapine

Drug: Tenofovir/emtricitabine

lopinavir/r and tenofovir/emtricitabine

Experimental group

Description:

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

Treatment:

Drug: ritonavir-boosted Lopinavir

Drug: Tenofovir/emtricitabine

Nevirapine and zidovudine/lamivudine

Active Comparator group

Description:

nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks

Treatment:

Drug: Zidovudine/lamivudine

Drug: nevirapine

Lopinavir/r and zidovudine/lamivudine

Experimental group

Description:

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

Treatment:

Drug: Zidovudine/lamivudine

Drug: ritonavir-boosted Lopinavir