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

Phase 3

Withdrawn

• Conditions: HIV
• Interventions: Drug: Lopinavir; Drug: Atazanavir

• Registration Number: NCT01255371
• Lead Sponsor: ANRS, Emerging Infectious Diseases

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-11-29
• Study First Submitted QC: 2010-12-06
• Study First Posted: 2010-12-07
• Study Start: 2012-03
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-07
• Last Update Posted: 2012-11-08
• Primary Completion: 2013-05
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A : Lopinavir	Lopinavir	Emtricitabine/tenofovir : * TDF300mg.FTC200mg (Fixed Dose Combination) * 1 tablet per day Lopinavir/ritonavir : * LPV200mg/RTV50mg * 2 tablets twice a day
Arm B : Atazanavir	Atazanavir	Lamivudine/tenofovir : * 3TC300mg/TDF300mg (Fixed Dose Combination) * 1 tablet per day Atazanavir/ritonavir : * ATV300mg/RTV100mg * 2 tablets once a day

Primary Outcome Measures

Name	Time	Method
Virological response	48 weeks	Proportion of patients with plasma HIV RNA \< 50 copies/mL

Secondary Outcome Measures

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

Trial Locations

Locations (2)

NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital; 🇹🇿 Mbeya, Tanzania

Tshepang clinic, Limpopo University; 🇿🇦 Pretoria, South Africa