A Multicentre Trial of Second-line Antiretroviral Treatment Strategies in African Adults Using Atazanavir or Lopinavir/Ritonavir

NCT01255371 | Withdrawn Phase 3 DMC

• 2 other identifiers: ANRS 12221 ALISAIP.07.33011.004
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

In the well recognized context of HIV infection chronicity, it is now crucial to identify and evaluate effective, well tolerated and affordable second line regimen in resources limited countries where patients often change treatment after a long period of viral replication while on first line regimen. This multicentre international, randomized, non-blinded phase III trial aim to demonstrate the non-inferiority of a generic lamivudine-tenofovir-atazanavir/ritonavir regimen (daily intake) as compared to a standard emtricitabine-tenofovir-lopinavir/ritonavir (twice daily intake)regimen for second line HIV-1 treatment. by stratifying on the viral load level (between 1000 and 5000 copies/mL versus \> 5000 copies/mL) at inclusion, this trial will also allow to evaluate the optimum moment for instituting the second-line treatment.

Conditions

HIV

Keywords

HIV; Second line antiretroviral treatment; Sub saharian Africa; Generic

Outcome Measures

Primary Outcomes (1)

• Virological response

  Proportion of patients with plasma HIV RNA \< 50 copies/mL

  48 weeks

Secondary Outcomes (7)

• Virological response

  12 and 24 weeks

• Viral resistance

  12, 24 and 48 weeks

• Clinical course of HIV infection

  Up to 48 weeks

• Tolerance assessment

  24 and 48 weeks

• Adherence assessment

  At each protocol visit : week 2, 4, 12, 24, 36 and 48

Study Arms (2)

Arm A : Lopinavir

ACTIVE COMPARATOR

Emtricitabine/tenofovir : * TDF300mg.FTC200mg (Fixed Dose Combination) * 1 tablet per day Lopinavir/ritonavir : * LPV200mg/RTV50mg * 2 tablets twice a day

Drug: Lopinavir

Arm B : Atazanavir

EXPERIMENTAL

Lamivudine/tenofovir : * 3TC300mg/TDF300mg (Fixed Dose Combination) * 1 tablet per day Atazanavir/ritonavir : * ATV300mg/RTV100mg * 2 tablets once a day

Drug: Atazanavir

Interventions

Lopinavir DRUG

Evaluation of second line antiretroviral regimen including boosted lopinavir

Arm A : Lopinavir

Atazanavir DRUG

Evaluation of second line antiretroviral regimen including boosted atazanavir

Arm B : Atazanavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18 and above
• out patient
• documented HIV-1 infection
• first line treatment failure:
• after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors
• two measurements of plasma HIV RNA levels \> 1000 copies/mL after at least 6 months of uninterrupted treatment or without any major modification
• satisfactory compliance (\>80%) to 1st line antiretroviral treatment
• signed informed consent
• agreement for contraception for women of childbearing age

You may not qualify if:

• HIV-2 infection or HIV-1/HIV-2 coinfection
• uncontrolled, ongoing opportunistic infection or of any severe or progressive disease including active TB
• first line antiretroviral treatment with a protease inhibitor or tenofovir
• ongoing treatment with rifampicin
• severe hepatic insufficiency (PT \< 50%)
• ALT \< 3 times the upper limit of normal
• creatinine clearance calculated by Cockcroft's formula \< 50 mL/min
• Hb \<=8 g/dL; platelets \< 50,000 cells/mm3; neutrophils \< 500 cells/mm3
• pregnancy and lactation

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Ludwig-Maximilians - University of Munich: collaborator
• Institute of Tropical Medicine, Belgium: collaborator
• Institut de Recherche pour le Developpement: collaborator
• Swiss National Science Foundation: collaborator
• University of Limpopo: collaborator
• NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania: collaborator

Study Sites (2)

Tshepang clinic, Limpopo University

Pretoria, South Africa

Location

NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital

Mbeya, Tanzania

Location

MeSH Terms

Interventions

Lopinavir; Atazanavir Sulfate

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Eric Delaporte

  Institut de Recherche pour le Developpement

  PRINCIPAL INVESTIGATOR

• Issakwisa Mwakyula

  NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital, Tanzania

  PRINCIPAL INVESTIGATOR

• Mzileni O Mogiyana

  University of Limpopo

  PRINCIPAL INVESTIGATOR

• Alexandra Calmy

  University of Geneva, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2010
• First Posted: December 7, 2010
• Study Start: March 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2014
• Last Updated: November 8, 2012

Record last verified: 2012-11

Locations

ZA (1); TA (1)