NCT01772940

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
425

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Dec 2008

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2008

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2011

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

January 14, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 21, 2013

Completed
Last Updated

August 26, 2013

Status Verified

August 1, 2013

Enrollment Period

2.8 years

First QC Date

January 14, 2013

Last Update Submit

August 22, 2013

Conditions

Keywords

First-line therapyProtease inhibitorNon-Nucleoside Reverse transcriptase InhibitorResource-limited setting

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • 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

  • Changes in laboratory parameters

    Through week 96

Study Arms (4)

nevirapine and tenofovir/emtricitabine

ACTIVE COMPARATOR

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

Drug: nevirapineDrug: Tenofovir/emtricitabine

lopinavir/r and tenofovir/emtricitabine

EXPERIMENTAL

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 LopinavirDrug: Tenofovir/emtricitabine

Nevirapine and zidovudine/lamivudine

ACTIVE COMPARATOR

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

Drug: nevirapineDrug: Zidovudine/lamivudine

Lopinavir/r and zidovudine/lamivudine

EXPERIMENTAL

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 LopinavirDrug: Zidovudine/lamivudine

Interventions

Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks

Also known as: Viramune
Nevirapine and zidovudine/lamivudinenevirapine and tenofovir/emtricitabine

ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks

Also known as: Aluvia
Lopinavir/r and zidovudine/lamivudinelopinavir/r and tenofovir/emtricitabine

tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks

Also known as: Truvada
lopinavir/r and tenofovir/emtricitabinenevirapine and tenofovir/emtricitabine

zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks

Also known as: Zidolam,combivir
Lopinavir/r and zidovudine/lamivudineNevirapine and zidovudine/lamivudine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cliniques Universitaires de Lubumbashi

Lubumbashi, Katanga, Republic of the Congo

Location

Related Publications (1)

  • Clumeck N, Mwamba C, Kabeya K, Matanda S, Vaira D, Necsoi C, Kadiebwe D, Delforge M, Kasamba E, Milolo C, Ilunga J, Kapend L. First-line antiretroviral therapy with nevirapine versus lopinavir-ritonavir based regimens in a resource-limited setting. AIDS. 2014 May 15;28(8):1143-53. doi: 10.1097/QAD.0000000000000214.

MeSH Terms

Interventions

Nevirapinelopinavir-ritonavir drug combinationTenofovirEmtricitabineEmtricitabine, Tenofovir Disoproxil Fumarate Drug Combinationlamivudine, zidovudine drug combination

Intervention Hierarchy (Ancestors)

PyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDrug CombinationsPharmaceutical Preparations

Study Officials

  • Nathan Clumeck, MD, PhD

    Centre Hospitalier Universitaire Saint Pierre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief infectious diseases , Professor of Medicine

Study Record Dates

First Submitted

January 14, 2013

First Posted

January 21, 2013

Study Start

December 1, 2008

Primary Completion

October 1, 2011

Study Completion

December 1, 2011

Last Updated

August 26, 2013

Record last verified: 2013-08

Locations