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

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.

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