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

NCT01127204 | Completed Phase 2 DMC

• 2 other identifiers: ANRS 12206 MONODIP.2007.33011.002
• Study Type: interventional
• Target: 161
• Locations: 2 countries
• Sites: 4

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.

Conditions

HIV Infections

Keywords

HIV; Antiretroviral therapy; Infant; Sub Saharian Africa

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Virological success

  12 months

• Immunological response

  12 and 25 months

• Antiretroviral and cotrimoxazol pharmacokinetic parameters

  6, 19 and 25 months

• Tolerance

  12 and 25 month

• Adherence

  12 and 25 months

Study Arms (2)

arm 1 (reference strategy)

ACTIVE COMPARATOR

AZT-3TC-LPV/r twice a day

Drug: AZT-3TC-LPV/r twice a day

arm 2 (simplification strategy)

EXPERIMENTAL

ABC-3TC-EFV once a day

Drug: ABC-3TC-EFV once a day

Interventions

AZT-3TC-LPV/r twice a day DRUG

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

arm 1 (reference strategy)

ABC-3TC-EFV once a day DRUG

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

arm 2 (simplification strategy)

Eligibility Criteria

• Age: 3 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• age 24 months at most
• virological success define as 2 consecutive indetectable HIV RNA measured by RT PCR at least 3 months apart.
• virological failure after the first 12 months of antiretroviral treatment

Sponsors & Collaborators

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

Study Sites (4)

Service de maladies infectieuses - CHU Charles de Gaulle

Ouagadougou, Burkina Faso

Location

Service de pédiatrie - CHU Yalgado Ouedraogo

Ouagadougou, Burkina Faso

Location

CEPREF

Abidjan, Côte d’Ivoire

Location

FSU abobo-Avocatier

Abidjan, Côte d’Ivoire

Location

Related Publications (7)

• 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.

  PMID: 34723858 DERIVED

• 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.

  PMID: 31334298 DERIVED

• 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.

  PMID: 28800382 DERIVED

• 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.

  PMID: 28483965 DERIVED

• 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.

  PMID: 28453240 DERIVED

• 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.

  PMID: 28434406 DERIVED

• 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.

  PMID: 27015798 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Marguerite Timite-Konan

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

  PRINCIPAL INVESTIGATOR

• Jules Mugabo

  Center for Infectious Desease Control - Kigali, Rwanda

  PRINCIPAL INVESTIGATOR

• Nicolas Meda

  Université de Ouagadougou - Ouagadougou, Burkina Faso

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 20, 2010
• Study Start: June 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: July 12, 2016

Record last verified: 2016-07

Locations

CÔ (2); BU (2)