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      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

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          Abstract

          Introduction: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years.

          Methods: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent’s consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed.

          Result s: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation.

          Conclusions: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.

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          Antiretroviral treatment for children with peripartum nevirapine exposure.

          Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings, but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis. The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown. We conducted a randomized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age, in six African countries, who qualified for treatment according to World Health Organization (WHO) criteria. Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis. The primary end point was virologic failure or discontinuation of treatment by study week 24. Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board. A total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P=0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events. Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission, antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir resulted in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine. Since nevirapine is used for both treatment and perinatal prevention of HIV infection in resource-limited settings, alternative strategies for the prevention of HIV transmission from mother to child, as well as for the treatment of HIV infection, are urgently required. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00307151.).
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            Viral suppression after 12 months of antiretroviral therapy in low- and middle-income countries: a systematic review

            OBJECTIVE: To establish estimates of viral suppression in low- and middle-income countries (LMICs) in patients who received antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection. METHODS: Data on viral suppression after 12 months of ART in LMICs were collected from articles published in 2003 to 2011 and from abstracts of conferences held between 2009 and 2011. Pooled proportions for on-treatment and intention-to-treat populations were used as summary estimates. Random-effects models were used for heterogeneous groups of studies (I² > 75%). FINDINGS: Overall, 49 studies covering 48 cohorts and 30 016 individuals met the inclusion criteria. With thresholds for suppression between 300 and 500 copies of viral ribonucleic acid (RNA) per ml of plasma, 84.3% (95% confidence interval, CI: 80.4-87.9) of the pooled on-treatment population and 70.5% (95% CI: 65.2-75.6) of the intention-to-treat population showed suppression. Use of different viral RNA thresholds changed the proportions showing suppression: to 84% and 76% of the on-treatment population with thresholds set above 300 and at or below 200 RNA copies per ml, respectively, and to 78%, 71% and 63% of the intention-to-treat population at thresholds set at 1000, 300 to 500, and 200 or fewer copies per ml, respectively. CONCLUSION: The pooled estimates of viral suppression recorded after 12 months of ART in LMICs provide benchmarks that other ART programmes can use to set realistic goals and perform predictive modelling. Evidence from this review suggests that the current international target - i.e. viral suppression in > 70% of the intention-to-treat population, with a threshold of 1000 copies per ml - should be revised upwards.
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              Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration.

              We investigated 18-month incidence and determinants of death and loss to follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. HIV-infected children (positive polymerase chain reaction 6 months). Data on 13,611 children, from Asia (N = 1454), East Africa (N = 3114), Southern Africa (N = 6212), and West Africa (N = 2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East Africa, 5.4% in Asia, 5.7% in Southern Africa, and 7.4% in West Africa (P = 0.01). Age < 24 months, World Health Organization stage 4, CD4 < 10%, attending a private sector clinic, larger cohort size, and living in West Africa were independently associated with poorer survival. The adjusted risk of loss to follow-up was 4.1% in Asia, 9.0% in Southern Africa, 14.0% in East Africa, and 21.8% in West Africa (P < 0.01). Age < 12 months, nonnucleoside reverse transcriptase inhibitor I-based ART regimen, World Health Organization stage 4 at ART start, ART initiation after 2005, attending a public sector or a nonurban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East Africa or West Africa were significantly associated with higher loss to follow-up. Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at the program level.
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                Author and article information

                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                ZIAS
                zias20
                Journal of the International AIDS Society
                Taylor & Francis
                1758-2652
                2017
                25 April 2017
                : 20
                : 1
                : 21362
                Affiliations
                [ a ] PACCI Programme, Site ANRS, MONOD Project , Abidjan, Côte d’Ivoire
                [ b ] MONOD Project, ANRS 12206, Centre de Recherche Internationale pour la Santé , Ouagadougou, Burkina Faso
                [ c ] Clinical Research department, Centre Muraz , Bobo-Dioulasso, Burkina Faso
                [ d ] Inserm, Unité U1219, Université Bordeaux , Bordeaux, France
                [ e ] Pediatric Department, Centre Hospitalier Universitaire of Cocody , Abidjan, Côte d’Ivoire
                [ f ] Virology departement, Laboratory CeDReS , Abidjan, Côte d’Ivoire
                [ g ] Laboratory, Centre Hospitalier Universitaire de Ouagadougou , Ouagadougou, Burkina Faso
                [ h ] EA 7327, Laboratoire de Virologie, Université Paris Descartes , CHU Necker, France
                [ i ] CePReF-enfants , Abidjan, Côte d’Ivoire
                [ j ] Pediatric Department, Centre Hospitalier Universitaire Yalgado Ouédraogo , Ouagadougou, Burkina Faso
                [ k ] Pediatric Department, Centre Hospitalier Universitaire de Yopougon , Abidjan, Côte d’Ivoire
                [ l ] Pediatric Department, Centre Hospitalier Universitaire Charles de Gaulle , Ouagadougou, Burkina Faso
                [ m ] EA 8, Université-Paris Descartes , Paris, France
                [ n ] Immunology, Hematology, Rhumatologie Unit, Hopital Necker Enfants Malades-Assistance Publique Hopitaux de Paris , Paris, France
                [ o ] Public Health department, University of Ouagadougou , Ouagadougou, Burkina Faso
                [ p ] Department of Infection and Immunity, Luxembourg Institute of Health , Luxembourg
                [ q ] Inserm, UMR1027, Université Paul Sabatier Toulouse 3 , Toulouse, France
                Author notes
                [ § ] Corresponding author: Valériane LEROY, Inserm UMR 1027, Epidémiologie et analyses en santé publique: risques, maladies chroniques et handicaps, Equipe 2: Axe santé de l’enfant et de l’adolescent en Afrique, Université Paul Sabatier Toulouse 3 , 37 Allées Jules Guesde, 31073 Toulouse Cedex 7, France. Tel: +33 5 61 14 59 57/+33 6 72 43 26 36. ( Valeriane.Leroy@ 123456inserm.fr )
                [*]

                See MONOD Study Group in the Acknowledgement section.

                Article
                1318525
                10.7448/IAS.20.01.21362
                5515025
                28453240
                cd323637-b137-4a93-9421-8770fd883489
                © 2017 Amani-Bosse C et al; licensee International AIDS Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 July 2016
                : 9 April 2017
                Page count
                Figures: 1, Tables: 6, References: 46, Pages: 14
                Funding
                Funded by: Institut National de la Santé et de la Recherche Médicale 10.13039/501100001677
                Funded by: ANRS 10.13039/501100003323
                Award ID: 12206
                Funded by: European and Developing Countries Clinical Trials Partnership 10.13039/501100001713
                Award ID: IP.2007.33011.002
                Funded by: Fonds National de la Recherche Luxembourg 10.13039/501100001866
                Désiré Dahourou is a fellow funded by the ANRS [ANRS12206-B89]. Malik Coulibaly was funded by EDCTP-ANRS-LIH.
                Categories
                Article
                Research Article

                Infectious disease & Microbiology
                hiv,children,early antiretroviral treatment,lopinavir,treatment outcomes,cohort,west africa

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