Clinical trial NCT01127204: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infections
Keywords: HIV
Antiretroviral therapy
Infant
Sub Saharian Africa
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: European and Developing Countries Clinical Trials Partnership (EDCTP)
name: Public Research Centre Health, Luxembourg
name: Ministry of Foreign Affairs, Luxembourg
name: University of Ouagadougou, Burkina Faso
name: Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire
name: Ministry of Health, Rwanda
name: Institut National de la Santé Et de la Recherche Médicale, France
name: University of Bordeaux
name: Institut de Sante Publique, d'Epidémiologie et de Développement
name: Université Montpellier
name: University of Paris 5 - Rene Descartes
name: Queen Fabiola Children's University Hospital
First posted: 2010-05-20
Enrollment: 161
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Initial therapeutic cohort: Virological success
timeFrame: 12 months
measure: Randomised simplification phase: Virological success
timeFrame: 25 months
Secondary outcomes:
measure: Virological success
timeFrame: 12 months
measure: Immunological response
timeFrame: 12 and 25 months
measure: Antiretroviral and cotrimoxazol pharmacokinetic parameters
timeFrame: 6, 19 and 25 months
measure: Tolerance
timeFrame: 12 and 25 month
measure: Adherence
timeFrame: 12 and 25 months
measure: Resistance to antiretroviral
timeFrame: 12 and 25 months
Other outcomes:
Locations:
city: Ouagadougou
country: Burkina Faso
facility: Service de maladies infectieuses - CHU Charles de Gaulle
city: Ouagadougou
country: Burkina Faso
facility: Service de pédiatrie - CHU Yalgado Ouedraogo
city: Abidjan
country: Côte D'Ivoire
facility: CEPREF
city: Abidjan
country: Côte D'Ivoire
facility: FSU abobo-Avocatier
Study officials:
affiliation: Service de pédiatrie - CHU Yopougon - Abidjan, Côte d'Ivoire
name: Marguerite Timite-Konan
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Infectious Desease Control - Kigali, Rwanda
name: Jules Mugabo
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Ouagadougou - Ouagadougou, Burkina Faso
name: Nicolas Meda
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.