Evaluation of Simplified Antiretroviral Treatment Strategies in HIV Infected Children Treated by Antiretroviral (ARV) Before One Year of Age

• Virological success [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  HIV RNA < 400 copies / mL
• Immunological response [ Time Frame: 12 and 25 months ] [ Designated as safety issue: No ]
  CD4+ lymphocyte absolute count and percentage
• Antiretroviral and cotrimoxazol pharmacokinetic parameters [ Time Frame: 6, 19 and 25 months ] [ Designated as safety issue: No ]
  The following parameters will be measured or calculated: maximal and minimal concentration (Cmax, Cmin), half life (t1/2), Aire Under the Curve (AUC), clearance and volume of distribution, for all antiretroviral (according to treatment arm : AZT, 3TC, LPV, ABC, EFV) and cotimoxazol.
• Tolerance [ Time Frame: 12 and 25 month ] [ Designated as safety issue: Yes ]
  occurence of grade 3 and 4 adverse events related to the trial treatment, particularly occurence of immune reconstitution inflammatory syndrom
• Adherence [ Time Frame: 12 and 25 months ] [ Designated as safety issue: Yes ]
  measurement at each protocol visit of the three last days treatment intake to be corelated to the antiretroviral concentration and virological success
• Resistance to antiretroviral [ Time Frame: 12 and 25 months ] [ Designated as safety issue: Yes ]
  Genotyping to analyse resistance mutation when virological failure

The MONOD trial aim to evaluate the implementation of early antiretroviral treatment strategies in HIV-infected infants and assess the feasibility and efficacy of simplifying the initial proposed regimen after a successful one year treatment. The initial treatment is AZT-3TC-LPV/r twice a day. After one year, the children will be randomized in one of the following : arm 1-reference AZT-3TC-LPV/r twice daily; arm 2-simplified ABC-3TC-EFV once daily.

The perspective of this project is to identify antiretroviral strategies to improve treatment access and adherence for children in sub-saharian Africa.

• Drug: AZT-3TC-LPV/r twice a day
  AZT sirup (10mg/ml): 4 mg/kg or 180 mg/m2 twice daily 3TC sirup (10mg/ml): 4 mg/kg twice daily LPV/r sirup (80/20 mg/ml): 12 mg/kg twice daily
• Drug: ABC-3TC-EFV once a day
  ABC sirup (20mg/ml): 16 mg/kg once daily in the morning 3TC sirup (10mg/ml): 8 mg/kg once daily in the morning EFV sirup (30mg/ml): 25 mg/kg once daily in the morning before food intake

• Active Comparator: arm 1 (reference strategy)
  AZT-3TC-LPV/r twice a day
  Intervention: Drug: AZT-3TC-LPV/r twice a day
• Experimental: arm 2 (simplification strategy)
  ABC-3TC-EFV once a day
  Intervention: Drug: ABC-3TC-EFV once a day

Inclusion Criteria for antiretroviral treatment initiation:

• infant follow-up in one of the trial site
• HIV-1 infection diagnose by RT PCR after 6 weeks of life
• age between 3 and 12 month at the antiretroviral treatment initiation
• naive of antiretrovirals except if received for the prevention of mother to child HIV transmission
• HB>=7 g/dl, neutrophiles>750/mm3, creatinin<3xULN, TGO and TGP<3xULN
• signed informed consent

Exclusion Criteria for antiretroviral treatment initiation:

• HIV-2 infection or HIV-1/HIV-2 co-infection
• Known intolerance to one of the trial treatment
• HB<7 g/dl, neutrophiles<750/mm3, creatinin>3xULN, TGO or TGP>3xULN

Inclusion Criteria for randomisation at 12 months in the simplification phase:

• age 24 months at most
• virological success define as 2 consecutive indetectable HIV RNA measured by RT PCR at least 3 months apart.

Exclusion Criteria for randomisation at 12 months in the simplification phase:

• virological failure after the first 12 months of antiretroviral treatment

• European and Developing Countries Clinical Trials Partnership (EDCTP)
• Public Research Centre Health, Luxembourg
• Ministry of Foreign Affairs, Luxembourg
• University of Ouagadougou, Burkina Faso
• Programme national,ANRS,Coopération française-Côte d'Ivoire (PAC-CI), Côte d'Ivoire
• Ministry of Health, Rwanda
• Institut National de la Santé Et de la Recherche Médicale, France
• University of Bordeaux
• Institut de Sante Publique, d'Epidémiologie et de Développement
• Université Montpellier
• University of Paris 5 - Rene Descartes
• Queen Fabiola Children's University Hospital