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

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Phase 3 Trial to Evaluate Two Simplified Antiretroviral Treatment Strategies in HIV Infected Children, Treated by Antiretroviral Triple Therapy Before One Year of Age, in Virological Success in Africa (Burkina Faso, Côte d'Ivoire, Rwanda)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: AZT-3TC-LPV/r twice a day
* Drug: ABC-3TC-EFV once a day


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: arm 1 (reference strategy)<br>AZT-3TC-LPV/r twice a day | Drug: AZT-3TC-LPV/r twice a day<br>* 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<br>|
| Experimental: arm 2 (simplification strategy)<br>ABC-3TC-EFV once a day | Drug: ABC-3TC-EFV once a day<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial therapeutic cohort: Virological success | survival without virological failure (death or loss of follow-up or virologic failure, i.e. HIV-ARN ≥400 copies/mL on one consecutive sample), analysis of resistance profile. | 12 months | 
| Randomised simplification phase: Virological success | survival without virological failure (death or loss of follow-up or virologic failure (HIV-ARN ≥400 copies/mL ))from M13 to M25. | 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological success | HIV RNA < 400 copies / mL | 12 months | 
| Immunological response | CD4+ lymphocyte absolute count and percentage | 12 and 25 months | 
| Antiretroviral and cotrimoxazol pharmacokinetic parameters | 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. | 6, 19 and 25 months | 
| Tolerance | occurence of grade 3 and 4 adverse events related to the trial treatment, particularly occurence of immune reconstitution inflammatory syndrome | 12 and 25 month | 
| Adherence | measurement at each protocol visit of the three last days treatment intake to be corelated to the antiretroviral concentration and virological success | 12 and 25 months | 
| Resistance to antiretroviral | Genotyping to analyse resistance mutation when virological failure | 12 and 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Antiretroviral therapy, Infant, Sub Saharian Africa