1. Short-Term Efficacy and Tolerance of ddI, 3TC, EFV regimen Once-Daily in HIV-1–Infected African Children: ANRS 12103 (Burkiname). Operational lessons from a clinical trial in children MSELLATI P 1, BARRO M 2, SOME J, 2 FOULONGNE V 3, DIASSO Y 2, ZOURE E 2, HIEN H 4, ROUET F 5, SEGONDY M 3, DRABO A 4, TAMBOURA H 2, OUIMINGA A 4, DIAGBOUGA S 4, HIEN A 2, YAMEOGO S 2, VAN de PERRE P 3, NACRO B 2. 1 UMI 233, IRD/UCAD/UM1/UY1, 2 CHU Bobo Dioulasso, Burkina Faso, 3 U INSERM 1058, Montpellier France, 4 Centre Muraz, Bobo Dioulasso, 5 CIRMF, Franceville, Gabon ANRS Symposium satellite, ICASA 2011, Addis Ababa

2. Context Access to antiretroviral therapy (ART) and routine laboratory monitoring are limited for HIV-1 infected children living in sub-Saharan Africa. A once a day intake of antiretrovirals could be an alternative to HAART current administration in children. A trial was conducted in Bobo-Dioulasso, Burkina Faso, to study the biological efficacy, tolerance and complinace of the combination of Didanosine (ddI), Lamivudine (3TC), Efavirenz (EFV) in once daily administration among HIV-1 infected children. ANRS Symposium satellite, ICASA 2011, Addis Ababa

3. Methods February 2006 to November 2007, – 51 HIV-1 infected children – from 30 months to 15 years and eligible for ART were enrolled in a phase II open clinical trial – follow up visits every three months. HIV-1 genotype testing was performed in children with PVL >1000 copies/ml after ART initiation. ANRS Symposium satellite, ICASA 2011, Addis Ababa

4. Results Children were followed for a median of 13.4 months (Inter quartile range [IQR] 12.8-14.2). At enrolment, – median CD4 count was 8% (IQR = 4.5-12). – median VL : 5.53 Log10 (IQR= 5.11 – 5.88) copies/mL. At 12 months – median CD4 increased significantly by +15% (p<10 -3 ), – median PVL decreases significantly by 5.46 Log copies/mL (p<10 -4 ). – Hemoglobin and platelets counts increased significantly by +1.05 g/dl (p<10 -5 ) and 108,500 cells/ml (p<10 -3 ), respectively. – Based on pill count, mean yearly adherence was 97.3% and 48% of the children had an adherence rate ≥ 95% at the four quarterly visits. Adherence was better for girls than for boys independently of other socio-demographic variables or markers of HIV disease progression. – Drug-resistance mutations were found in 11 children (21.6%). ANRS Symposium satellite, ICASA 2011, Addis Ababa

5. Conclusion of the trial This once daily drug combination is associated with a good virological efficacy, immune reconstitution and adherence. However the high prevalence of drug resistance mutations is a matter of concern and impairs the results of the study. ANRS Symposium satellite, ICASA 2011, Addis Ababa

6. What do we learned from an operational point of view (1) They were no lost to follow-up – Community support, Home visits, Middle size town We were able to do pharmacokinetics studies and we miss desperately such studies in children in Africa – When needed, we offered hospitalization to mother and child to allow the blood sampling Compliance tools we used were not really appropriate ANRS Symposium satellite, ICASA 2011, Addis Ababa

7. What do we learned from an operational point of view (2) This regimen is interesting in children who go to school or for families where parents are both working. When using such a drug regimen, you must be sure of an excellent compliance. During the time we realized this trial, fixed dose combinations and one intake a day regimen were produced. ANRS Symposium satellite, ICASA 2011, Addis Ababa