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

• ClinicalTrials.gov Identifier: NCT01127204
• Recruitment Status: Completed
• First Posted: May 20, 2010
• Last Update Posted: July 12, 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
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: AZT-3TC-LPV/r twice a day; Drug: ABC-3TC-EFV once a day	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: June 2011
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: April 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Initial therapeutic cohort: Virological success [ Time Frame: 12 months ]
   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.
2. Randomised simplification phase: Virological success [ Time Frame: 25 months ]
   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 :

1. Virological success [ Time Frame: 12 months ]
   HIV RNA < 400 copies / mL
2. Immunological response [ Time Frame: 12 and 25 months ]
   CD4+ lymphocyte absolute count and percentage
3. Antiretroviral and cotrimoxazol pharmacokinetic parameters [ Time Frame: 6, 19 and 25 months ]
   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.
4. Tolerance [ Time Frame: 12 and 25 month ]
   occurence of grade 3 and 4 adverse events related to the trial treatment, particularly occurence of immune reconstitution inflammatory syndrome
5. Adherence [ Time Frame: 12 and 25 months ]
   measurement at each protocol visit of the three last days treatment intake to be corelated to the antiretroviral concentration and virological success
6. Resistance to antiretroviral [ Time Frame: 12 and 25 months ]
   Genotyping to analyse resistance mutation when virological failure

Eligibility Criteria

• Ages Eligible for Study: 3 Months to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Burkina Faso

Service de maladies infectieuses - CHU Charles de Gaulle

Ouagadougou, Burkina Faso

Service de pédiatrie - CHU Yalgado Ouedraogo

Ouagadougou, Burkina Faso

Côte D'Ivoire

CEPREF

Abidjan, Côte D'Ivoire

FSU abobo-Avocatier

Abidjan, Côte D'Ivoire

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

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

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT01127204
• Other Study ID Numbers: ANRS 12206 MONOD; IP.2007.33011.002 ( Other Grant/Funding Number: EDCTP )
• First Posted: May 20, 2010
• Last Update Posted: July 12, 2016
• Last Verified: July 2016

Keywords provided by ANRS, Emerging Infectious Diseases:

HIV; Antiretroviral therapy; Infant; Sub Saharian Africa

Additional relevant MeSH terms:

HIV Infections; 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; Lamivudine; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; Anti-Retroviral Agents