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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

AZT-3TC-LPV/r twice a day

ABC-3TC-EFV once a day

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, Antiretroviral therapy, Infant, Sub Saharian Africa

Eligibility Criteria

3 Months - 12 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Service de maladies infectieuses - CHU Charles de Gaulle
Service de pédiatrie - CHU Yalgado Ouedraogo
CEPREF
FSU abobo-Avocatier

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

arm 1 (reference strategy)

arm 2 (simplification strategy)

Arm Description

AZT-3TC-LPV/r twice a day

ABC-3TC-EFV once a day

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Virological success

HIV RNA < 400 copies / mL

Immunological response

CD4+ lymphocyte absolute count and percentage

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.

Tolerance

occurence of grade 3 and 4 adverse events related to the trial treatment, particularly occurence of immune reconstitution inflammatory syndrome

Adherence

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

Genotyping to analyse resistance mutation when virological failure

Full Information

NCT ID

NCT01127204

First Posted

May 19, 2010

Last Updated

July 11, 2016

Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

European and Developing Countries Clinical Trials Partnership (EDCTP), Public Research Centre Health, Luxembourg, Ministry of Foreign Affairs, Luxembourg, University of Ouagadougou, Burkina Faso, Programme PAC-CI, Site ANRS-MIE de 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

1. Study Identification

Unique Protocol Identification Number

NCT01127204

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

June 2011 (undefined)

Primary Completion Date

April 2015 (Actual)

Study Completion Date

April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ANRS, Emerging Infectious Diseases

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

HIV, Antiretroviral therapy, Infant, Sub Saharian Africa

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

161 (Actual)

8. Arms, Groups, and Interventions

Arm Title

arm 1 (reference strategy)

Arm Type

Active Comparator

Arm Description

AZT-3TC-LPV/r twice a day

Arm Title

arm 2 (simplification strategy)

Arm Type

Experimental

Arm Description

ABC-3TC-EFV once a day

Intervention Type

Drug

Intervention Name(s)

AZT-3TC-LPV/r twice a day

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

ABC-3TC-EFV once a day

Intervention Description

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

Primary Outcome Measure Information:

Title

Initial therapeutic cohort: Virological success

Description

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.

Time Frame

12 months

Title

Randomised simplification phase: Virological success

Description

survival without virological failure (death or loss of follow-up or virologic failure (HIV-ARN ≥400 copies/mL ))from M13 to M25.

Time Frame

25 months

Secondary Outcome Measure Information:

Title

Virological success

Description

HIV RNA < 400 copies / mL

Time Frame

12 months

Title

Immunological response

Description

CD4+ lymphocyte absolute count and percentage

Time Frame

12 and 25 months

Title

Antiretroviral and cotrimoxazol pharmacokinetic parameters

Description

Time Frame

6, 19 and 25 months

Title

Tolerance

Description

occurence of grade 3 and 4 adverse events related to the trial treatment, particularly occurence of immune reconstitution inflammatory syndrome

Time Frame

12 and 25 month

Title

Adherence

Description

measurement at each protocol visit of the three last days treatment intake to be corelated to the antiretroviral concentration and virological success

Time Frame

12 and 25 months

Title

Resistance to antiretroviral

Description

Genotyping to analyse resistance mutation when virological failure

Time Frame

12 and 25 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Months

Maximum Age & Unit of Time

12 Months

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marguerite Timite-Konan

Organizational Affiliation

Service de pédiatrie - CHU Yopougon - Abidjan, Côte d'Ivoire

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jules Mugabo

Organizational Affiliation

Center for Infectious Desease Control - Kigali, Rwanda

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Nicolas Meda

Organizational Affiliation

Université de Ouagadougou - Ouagadougou, Burkina Faso

Official's Role

Principal Investigator

Facility Information:

Facility Name

Service de maladies infectieuses - CHU Charles de Gaulle

City

Ouagadougou

Country

Burkina Faso

Facility Name

Service de pédiatrie - CHU Yalgado Ouedraogo

City

Ouagadougou

Country

Burkina Faso

Facility Name

CEPREF

City

Abidjan

Country

Côte D'Ivoire

Facility Name

FSU abobo-Avocatier

City

Abidjan

Country

Côte D'Ivoire

12. IPD Sharing Statement

Citations:

PubMed Identifier

34723858

Citation

Pressiat C, Toni TD, Treluyer JM, Yonaba C, Dahourou DL, Malateste K, Seguin-Devaux C, Leroy V, Hirt D; MONOD ANRS Study Group. High nevirapine levels in breast milk and consequences in HIV-infected child when initiated on antiretroviral therapy. AIDS. 2021 Nov 15;35(14):2409-2410. doi: 10.1097/QAD.0000000000003043. No abstract available.

Results Reference

derived

PubMed Identifier

31334298

Citation

Desmonde S, Frank SC, Coovadia A, Dahourou DL, Hou T, Abrams EJ, Amorissani-Folquet M, Walensky RP, Strehlau R, Penazzato M, Freedberg KA, Kuhn L, Leroy V, Ciaranello AL. Cost-Effectiveness of Preemptive Switching to Efavirenz-Based Antiretroviral Therapy for Children With Human Immunodeficiency Virus. Open Forum Infect Dis. 2019 Jun 11;6(7):ofz276. doi: 10.1093/ofid/ofz276. eCollection 2019 Jul.

Results Reference

derived

PubMed Identifier

28800382

Citation

Pressiat C, Mea-Assande V, Yonaba C, Treluyer JM, Dahourou DL, Amorissani-Folquet M, Blanche S, Eboua F, Ye D, Lui G, Malateste K, Zheng Y, Leroy V, Hirt D; MONOD Study Group. Suboptimal cotrimoxazole prophylactic concentrations in HIV-infected children according to the WHO guidelines. Br J Clin Pharmacol. 2017 Dec;83(12):2729-2740. doi: 10.1111/bcp.13397. Epub 2017 Sep 20.

Results Reference

derived

PubMed Identifier

28483965

Citation

Pressiat C, Amorissani-Folquet M, Yonaba C, Treluyer JM, Dahourou DL, Eboua F, Blanche S, Mea-Assande V, Bouazza N, Foissac F, Malateste K, Ouedraogo S, Lui G, Leroy V, Hirt D. Pharmacokinetics of Efavirenz at a High Dose of 25 Milligrams per Kilogram per Day in Children 2 to 3 Years Old. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e00297-17. doi: 10.1128/AAC.00297-17. Print 2017 Jul.

Results Reference

derived

PubMed Identifier

28453240

Citation

Amani-Bosse C, Dahourou DL, Malateste K, Amorissani-Folquet M, Coulibaly M, Dattez S, Emieme A, Barry M, Rouzioux C, N'gbeche S, Yonaba C, Timite-Konan M, Mea V, Ouedraogo S, Blanche S, Meda N, Seguin-Devaux C, Leroy V. Virological response and resistances over 12 months among HIV-infected children less than two years receiving first-line lopinavir/ritonavir-based antiretroviral therapy in Cote d'Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort. J Int AIDS Soc. 2017 Apr 25;20(1):21362. doi: 10.7448/IAS.20.01.21362.

Results Reference

derived

PubMed Identifier

28434406

Citation

Dahourou DL, Amorissani-Folquet M, Malateste K, Amani-Bosse C, Coulibaly M, Seguin-Devaux C, Toni T, Ouedraogo R, Blanche S, Yonaba C, Eboua F, Lepage P, Avit D, Ouedraogo S, Van de Perre P, N'Gbeche S, Kalmogho A, Salamon R, Meda N, Timite-Konan M, Leroy V; MONOD Study Group. Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and Cote d'Ivoire: the MONOD ANRS 12206 non-inferiority randomised trial. BMC Med. 2017 Apr 24;15(1):85. doi: 10.1186/s12916-017-0842-4.

Results Reference

derived

PubMed Identifier

27015798

Citation

Dahourou DL, Amorissani-Folquet M, Coulibaly M, Avit-Edi D, Meda N, Timite-Konan M, Arendt V, Ye D, Amani-Bosse C, Salamon R, Lepage P, Leroy V; Monod Anrs 12206 Study Group. Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013. J Int AIDS Soc. 2016 Mar 23;19(1):20601. doi: 10.7448/IAS.19.1.20601. eCollection 2016.

Results Reference

derived

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

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