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

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: AZT-3TC-LPV/r twice a day; Drug: ABC-3TC-EFV once a day

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Burkina Faso
  • Ouagadougou, Burkina Faso
    • Service de maladies infectieuses - CHU Charles de Gaulle
  • Ouagadougou, Burkina Faso
    • Service de pédiatrie - CHU Yalgado Ouedraogo
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • CEPREF
  • Abidjan, Côte D'Ivoire
    • FSU abobo-Avocatier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: May 19, 2010
• First Submitted That Met QC Criteria: May 19, 2010
• First Posted (Estimate): May 20, 2010

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: HIV; Infant; Antiretroviral therapy; Sub Saharian Africa
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine
• Other Study ID Numbers: ANRS 12206 MONOD; IP.2007.33011.002 (Other Grant/Funding Number: EDCTP)