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

HIV Infections Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01127204
• Other study ID #: ANRS 12206 MONOD
• Secondary ID: IP.2007.33011.00
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 19, 2010
• Last updated: July 11, 2016
• Start date: June 2011
• Est. completion date: April 2015

Study information

• Verified date: July 2016
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Burkina Faso: Ministry of HealthCote d'Ivoire: Ministry of Health and Public HygieneRwanda: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 12 Months

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

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
• 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

Locations

Country	Name	City	State
Burkina Faso	Service de maladies infectieuses - CHU Charles de Gaulle	Ouagadougou
Burkina Faso	Service de pédiatrie - CHU Yalgado Ouedraogo	Ouagadougou
Côte D'Ivoire	CEPREF	Abidjan
Côte D'Ivoire	FSU abobo-Avocatier	Abidjan

Sponsors (13)

Lead Sponsor

Collaborator

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

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

Countries where clinical trial is conducted

Burkina Faso,  Côte D'Ivoire, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	Virological success	HIV RNA < 400 copies / mL	12 months	No
Secondary	Immunological response	CD4+ lymphocyte absolute count and percentage	12 and 25 months	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	Resistance to antiretroviral	Genotyping to analyse resistance mutation when virological failure	12 and 25 months	Yes