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

A Multicenter Phase III Trial of Second-line Antiretroviral Treatment Strategies in African Adults (Tanzania Ans South Africa) Using Atazanavir or Lopinavir/Ritonavir

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.

Study Overview

• Status: Withdrawn
• Conditions: HIV
• Intervention / Treatment: Drug: Lopinavir; Drug: Atazanavir

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Pretoria, South Africa
    • Tshepang clinic, Limpopo University
• Tanzania
  • Mbeya, Tanzania
    • NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A : Lopinavir; Emtricitabine/tenofovir : TDF300mg.FTC200mg (Fixed Dose Combination); 1 tablet per day Lopinavir/ritonavir : LPV200mg/RTV50mg; 2 tablets twice a day	Drug: Lopinavir; Evaluation of second line antiretroviral regimen including boosted lopinavir
Experimental: Arm B : Atazanavir; Lamivudine/tenofovir : 3TC300mg/TDF300mg (Fixed Dose Combination); 1 tablet per day Atazanavir/ritonavir : ATV300mg/RTV100mg; 2 tablets once a day	Drug: Atazanavir; Evaluation of second line antiretroviral regimen including boosted atazanavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological response	Proportion of patients with plasma HIV RNA < 50 copies/mL	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological response	Proportion of patients with plasma HIV RNA < 400 copies/mL	12 and 24 weeks
Viral resistance	Incidence of resistance mutations after treatment failure (HIV RNA < 1000 copies/mL)	12, 24 and 48 weeks
Clinical course of HIV infection	Mortality, occurence of clinical events stage 3 or 4 (WHO classification), immune reconstitution sundrome, non-AIDS clinical events including bacterial infections	Up to 48 weeks
Tolerance assessment	Proportion of adverse events related to antiretroviral treatment, proportion of treatement discontinuations due to antiretroviral side effect, variation of biological parameters and metabolic markers between second line antiretroviral initiation and 24/48 weeks.	24 and 48 weeks
Adherence assessment	Measurement of pills consumption at each visit, face-to-face questionnaire with the pharmacist	At each protocol visit : week 2, 4, 12, 24, 36 and 48
Hepatitis B evaluation	Prevalence of HBs AG, HBe Ag, HBV viremia, and HBV asociated drug resistance mutations at baseline	At entry
Immunologic response	Variation of circulating total and CD4+ lymphocyte count between second line treatment initiation and 24 weeks/48 weeks	24 and 48 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: November 29, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (Estimate): December 7, 2010

Study Record Updates

• Last Update Posted (Estimate): November 8, 2012
• Last Update Submitted That Met QC Criteria: November 7, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: HIV; Second line antiretroviral treatment; Sub saharian Africa; Generic
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Lopinavir; Atazanavir Sulfate
• Other Study ID Numbers: ANRS 12221 ALISA; IP.07.33011.004 (Other Grant/Funding Number: EDCTP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No