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

HIV Clinical Trial

— ALISA  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01255371
• Other study ID #: ANRS 12221 ALISA
• Secondary ID: IP.07.33011.004
• Status: Withdrawn
• Phase: Phase 3
• First received: November 29, 2010
• Last updated: November 7, 2012
• Start date: March 2012
• Est. completion date: December 2014

Study information

• Verified date: November 2012
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Tanzania: Ministry of HealthSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2014
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Lopinavir
Evaluation of second line antiretroviral regimen including boosted lopinavir
• Atazanavir
Evaluation of second line antiretroviral regimen including boosted atazanavir

Locations

Country	Name	City	State
South Africa	Tshepang clinic, Limpopo University	Pretoria
Tanzania	NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital	Mbeya

Sponsors (8)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	European and Developing Countries Clinical Trials Partnership (EDCTP), Institut de Recherche pour le Developpement, France, Institute of Tropical Medicine, Belgium, Ludwig-Maximilians - University of Munich, NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania, Swiss National Science Foundation, University of Limpopo

Countries where clinical trial is conducted

South Africa,  Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virological response	Proportion of patients with plasma HIV RNA < 50 copies/mL	48 weeks	No
Secondary	Virological response	Proportion of patients with plasma HIV RNA < 400 copies/mL	12 and 24 weeks	No
Secondary	Viral resistance	Incidence of resistance mutations after treatment failure (HIV RNA < 1000 copies/mL)	12, 24 and 48 weeks	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	Hepatitis B evaluation	Prevalence of HBs AG, HBe Ag, HBV viremia, and HBV asociated drug resistance mutations at baseline	At entry	No
Secondary	Immunologic response	Variation of circulating total and CD4+ lymphocyte count between second line treatment initiation and 24 weeks/48 weeks	24 and 48 weeks	No