Once-daily Highly Active Antiretroviral Treatment Regimen Administration in HIV-1 Infected Children in Burkina Faso (ANRS 12103 BURKINAME)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to try a known antiretroviral combination in HIV- infected children with only one intake a day, in order to simplify the prescription and improve adherence to treatment. This is what is called a phase II clinical trial, only recruiting and following a small number of children (50) during one year to evaluate the quantity of drug in the blood just before it is taken and one to three hours after it is taken. The other important objective is to study the tolerance of drugs in that mode of prescription of the triple combination.

Detailed Description
-----------------
The data relating to pharmacology tolerance and efficacy of the once-daily combination of 3TC + ddI + EFV have never been studied. This regimen may lead to a better treatment of the HIV-1 infected children in developing countries, as well as in Europe. Because of its simplicity it would facilitate observance that is one of the essential parameters of efficacy of treatments. The main objectives are those of a phase II clinical trial: Assess the virological and immunological efficacy of a once daily HAART regimen comprising lamivudine (3TC) + didanosine (ddI) + efavirenz (EFV) [pediatric reference]; Analyse the pharmacological characteristics of this combination in children; Assess the tolerance; Study the appearance of resistance; Evaluate the observance to treatment. 50 HIV-1 infected children aged 30 months to 15 years whose clinical and immunological state (stage B or C) requires antiretroviral treatment, will be included in the study. They should be naive of any ARV treatment (except the treatment received in the framework of PMTCT (Prevention of Mother to Child Transmission). Data Collection and Development of the Study: Monthly clinical examination; RNA HIV-1 and CD4 counts; Pharmacological dosages; Haematology and biochemistry surveillance; Genotypic resistance at inclusion; and, in case of unsuccess or failure, Assessment of observance according to alternate methods. Laboratory examinations will be carried out at Centre Muraz except for genotyping and for pharmacological tests sent to Montpellier Teaching Hospital (France).

Official Title
-----------------
HAART Regimen Comprising 3TC + ddI + EFV in Once-daily Administration in HIV-1 Infected Children in Burkina Faso

Conditions
-----------------
HIV Infections, AIDS

Intervention / Treatment
-----------------
* Drug: Efavirenz (EFV)
* Drug: Lamivudine (3TC)
* Drug: Didanosine (ddI)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV-1 infected children Weight over 12 kgs Age over 30 months Clinical stage requiring HAART Naive to antiretroviral treatment (except PMTCT prophylaxis) Mother's or tutor's informed consent signed Exclusion Criteria: HIV-2 or dual HIV infection Previous antiretroviral therapy Children unable to swallow pills Known resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI)

Ages Eligible for Study
-----------------
Minimum Age: 30 Months
Maximum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Efavirenz (EFV)|nan|
|Drug: Lamivudine (3TC)|nan|
|Drug: Didanosine (ddI)|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with HIV RNA less than 400 copies per ml and less than 50 copies per ml at month 12 (M12) |  | 12 and 24 months | 
| Cmin and Cmax for the three drugs |  | 15 days | 
| Grade 3 or 4 undesirable effects frequency |  | through out the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with CD4 greater than 25 percent at M12 and M24 |  | 12 and 24 months | 
| Amplitude of viral load reduction |  | 12 and 24 months | 
| Slope of CD4 compared with the initial values |  | 12 and 24 months | 
| Percentage of patients lost to follow-up |  | 12 and 24 months | 
| Percentage of deaths and of B or C classing events |  | Through out the trial | 
| Percentage of treatment interruption |  | Through out the trial | 
| Percentage and type of resistance mutations |  | 12 and 24 months | 
| Percentage of patients forgetting more than one pill within the last three days |  | Through out the trial | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HAART, once-daily, child, africa, HIV, AIDS, Treatment Naive