Clinical trial NCT01255371: A Multicentre Trial of Second-line Antiretroviral Treatment Strategies in African Adults Using Atazanavir or Lopinavir/Ritonavir
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: HIV
Keywords: HIV
Second line antiretroviral treatment
Sub saharian Africa
Generic
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: Ludwig-Maximilians - University of Munich
name: Institute of Tropical Medicine, Belgium
name: Institut de Recherche pour le Developpement
name: Swiss National Science Foundation
name: University of Limpopo
name: NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania
First posted: 2010-12-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Virological response
timeFrame: 48 weeks
Secondary outcomes:
measure: Virological response
timeFrame: 12 and 24 weeks
measure: Viral resistance
timeFrame: 12, 24 and 48 weeks
measure: Clinical course of HIV infection
timeFrame: Up to 48 weeks
measure: Tolerance assessment
timeFrame: 24 and 48 weeks
measure: Adherence assessment
timeFrame: At each protocol visit : week 2, 4, 12, 24, 36 and 48
measure: Hepatitis B evaluation
timeFrame: At entry
measure: Immunologic response
timeFrame: 24 and 48 weeks
Other outcomes:
Locations:
city: Pretoria
country: South Africa
facility: Tshepang clinic, Limpopo University
city: Mbeya
country: Tanzania
facility: NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Eric Delaporte
role: PRINCIPAL_INVESTIGATOR
affiliation: NIMR-Mbeya Medical Research Program-Mbeya Referral Hospital, Tanzania
name: Issakwisa Mwakyula
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Limpopo
name: Mzileni O Mogiyana
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Geneva, Switzerland
name: Alexandra Calmy
role: PRINCIPAL_INVESTIGATOR
References: