Evaluation of three 2 nd Line Antiretroviral regimens in Africa (Dakar, Yaounde) « 2 LADY » ANRS project

Promotor : - ANRS (JF Delfraissy) P.I : - Sinata Koulla Shiro (Cameroun) - P. Salif Sow(Sénégal) - E. Delaporte (IRD&CHU,Montpellier,France) CO-PI: - A.Calmy (MSF/Cameroun &HCUG,Suisse) - P.M Girard IMEA, Paris Methodological center : - V. Le Moing (UMR 145, Montpellier)

Rationale (1) 2 million people are on ART (28% of those in need !) AZT or d4T + 3TC and 1 NNRTI predominate in first line To simplify second line therapy options (programatic level, cost,…)

Rationale (2) « Prioritizing second line ART within public health approach » (WHO 2006, 2007) Second line regimens have not been rigourosly evaluated in the context of limited resources Other option can be considered

NRTI componentPI component TDF+3TC ABC+ddI ATV/r RTV 1 LPV/r TDF+ddI 2 ddI+3TC TDF+ABC AZT+TDF AZT+3TC+TDF ABC+3TC SQV/r IDV/r AZT+ddI AZT+3TC AZT+3TC+ABC FPV/r 1 RTV was rated only as a pharmacolgical booster for other Pis. 2 The combinattion of TDF/ddI was rated with consideration of a dose reduction of ddi to mg OD according to body weight. Regimens when thymidine analogs are used in 1 st line therapy WHO 2007 Urgent HightImportant

Objectives of the study Main objective In case of virological failure to a first line ART To compare the virological response at week 48 of three different second line regimens :  FTC/3TC - TDF - Lopinavir/R WHO  Abacavir - ddi - Lopinavir/RPriorities and « Innovative strategy » with new ARV FTC-TDF-Darunavir/R

Secondary objectives : To compare :  Clinical progression  Virological response at week 24  Immunological response  Tolerance  Adherence

Design Methods : Randomised,unblinded, no inferiority comparative trial in HIV-1 infected patients with HIVRNA > 1000c/ml, on a first line ARV since at least 12 months with 2 NRTI and 1 NNRTI Number of patients : n = 150 x3

Feasability : Cameroun : Yaounde : Central Hospital (n= 5000) General Hospital (n= 1000) Douala : (MS F-CH project) n= 4000 patients under HAART Senegal : Dakar CHU Fann n= 1500

Calendar and Questions The protocol has been approved by ANRS and is funded TIBOTEC for darunavir (5years)AND TMC125 (salvage therapy) :contract to be finalized Protocol ready to be submitted for ethical/administrative clearences Begin expected end 2008

EDCTP 2 LADY plus Tanzania,South Africa,Germany,Belgium

Arm 1 TDF - 3TC - LPV n ≈ 120 Arm A TDF - 3TC - LPV n = 335 Arm 3 LPV monotherapy n ≈ 240 Arm B ABC - DDI - LPV n = 335 Arm 2 ABC - DDI - LPV n ≈ 120 Day 0 1 st randomization W52 2 nd randomization W48 1 st analysis W100 2 nd analysis Phase 2Phase 1