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

This study has been completed.
Sponsor:
Collaborators:
University Hospital of Liege
Ministry of Public Health, Democratic Republic of the Congo
Pierre and Marie Curie University
University Paris 7 - Denis Diderot
Gilead Sciences
Abbott
Information provided by (Responsible Party):
Clumeck Nathan, Centre Hospitalier Universitaire Saint Pierre
ClinicalTrials.gov Identifier:
NCT01772940
First received: January 14, 2013
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: nevirapine
Drug: ritonavir-boosted Lopinavir
Drug: Tenofovir/emtricitabine
Drug: Zidovudine/lamivudine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Nevirapine vs Ritonavir-boosted Lopinavir in ART HIV-infected Adults in a Resource-limited Setting; a Randomized, Multicenter, Parallel Group Study

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Saint Pierre:

Primary Outcome Measures:
  • Incidence of therapeutic failure [ Time Frame: At week 48 with follow-up until week 96 ] [ Designated as safety issue: Yes ]

    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:
  • HIV-1 RNA viral load less than 50 copies/ml [ Time Frame: Through week 96 ] [ Designated as safety issue: No ]
    The percentage of patients with HIV-1 RNA < 50 copies/ml

  • Immunologic response [ Time Frame: Through week 96 ] [ Designated as safety issue: No ]
    Cluster of differentiation 4 (CD4) cell count change from baseline

  • HIV-1 resistance mutations [ Time Frame: At baseline and at the time of virologic failure ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Through week 96 ] [ Designated as safety issue: Yes ]
    Incidence of adverse events and laboratory abnormalities

  • Changes in laboratory parameters [ Time Frame: Through week 96 ] [ Designated as safety issue: No ]

Enrollment: 425
Study Start Date: December 2008
Study Completion Date: December 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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
Drug: nevirapine
Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks
Other Name: Viramune
Drug: Tenofovir/emtricitabine
tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks
Other Name: Truvada
Experimental: 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
Drug: ritonavir-boosted Lopinavir
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks
Other Name: Aluvia
Drug: Tenofovir/emtricitabine
tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks
Other Name: Truvada
Active Comparator: Nevirapine and zidovudine/lamivudine
nevirapine 200 mg/zidovudine 300 mg/lamivudine 150 mg (fixed-dose combination) twice daily, per os for 96 weeks
Drug: nevirapine
Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks
Other Name: Viramune
Drug: Zidovudine/lamivudine
zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks
Other Name: Zidolam,combivir
Experimental: 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
Drug: ritonavir-boosted Lopinavir
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks
Other Name: Aluvia
Drug: Zidovudine/lamivudine
zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks
Other Name: Zidolam,combivir

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772940

Locations
Congo
Cliniques Universitaires de Lubumbashi
Lubumbashi, Katanga, Congo
Sponsors and Collaborators
Centre Hospitalier Universitaire Saint Pierre
University Hospital of Liege
Ministry of Public Health, Democratic Republic of the Congo
Pierre and Marie Curie University
University Paris 7 - Denis Diderot
Gilead Sciences
Abbott
Investigators
Principal Investigator: Nathan Clumeck, MD, PhD Centre Hospitalier Universitaire Saint Pierre
  More Information

No publications provided by Centre Hospitalier Universitaire Saint Pierre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clumeck Nathan, Chief infectious diseases , Professor of Medicine, Centre Hospitalier Universitaire Saint Pierre
ClinicalTrials.gov Identifier: NCT01772940     History of Changes
Other Study ID Numbers: Lubumbashi trial
Study First Received: January 14, 2013
Last Updated: August 22, 2013
Health Authority: Belgium: Ministry of Social Affairs, Public Health and the Environment

Keywords provided by Centre Hospitalier Universitaire Saint Pierre:
First-line therapy
Protease inhibitor
Non-Nucleoside Reverse transcriptase Inhibitor
Resource-limited setting

Additional relevant MeSH terms:
Reverse Transcriptase Inhibitors
Nevirapine
Tenofovir
Tenofovir disoproxil
Lamivudine
Zidovudine
Emtricitabine
Lopinavir
Ritonavir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents
Antimetabolites

ClinicalTrials.gov processed this record on October 19, 2014