Jean-Christophe Beghin1, Jean Ruelle2, Patrick Goubau3, Dimitri Van der Linden4. 1. Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles (ULB), Pediatric Pulmonology, Brussels, Belgium; Université Catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium; Université Catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium. Electronic address: jean-christophe.beghin@huderf.be. 2. Université Catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium; Cliniques Universitaires St Luc, Laboratories Department, Brussels, Belgium. Electronic address: jean.ruelle@uclouvain.be. 3. Université Catholique de Louvain, AIDS Reference Laboratory, Brussels, Belgium; Université Catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium. Electronic address: patrick.goubau@uclouvain.be. 4. Université Catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium; Cliniques Universitaires St Luc, Pediatric Infectious Diseases, General Pediatrics, Pediatric Department, Brussels, Belgium. Electronic address: dimitri.vanderlinden@uclouvain.be.
Abstract
INTRODUCTION: Management of antiretroviral-drug resistance in HIV-infected children is a global health concern. We compared the long-term virological outcomes of two cohorts of children living in a rural setting of South Africa. The first cohort initiated treatment before one year and the second after two years of age. The aim of this study was to describe the long-term consequences of early treatment initiation in terms of viral load and drug-resistance. METHODS: This retrospective study was conducted at the Edendale Hospital located in a peri-urban area of KwaZulu-Natal. Children were included during their planned appointment. Drug resistance was assessed genotypically on proviral DNA. RESULTS: From the 161 children included in this study, 93 samples were successfully genotyped. Both cohorts had comparable viral loads, but children treated early more often presented NRTI or NNRTI mutations, while there was no difference for PI mutations rates. CONCLUSIONS: Treatment was highly effective when comparing virological outcomes in both early- and late-treated cohorts. The persistence of NNRTI mutations could lead to treatment failures in children older than 3 years initiating their therapy with a NNRTI, or for those switching from a PI to NNRTI based regimen. The accumulation of NRTI mutations may lead to a functional PI monotherapy and consequently to viral escape. To promote access to HIV genotyping in resource-limited settings is challenging but essential to avoid inappropriate therapy switches in case of virological failure, and to adapt national treatment guidelines in line with the epidemiology of resistance.
INTRODUCTION: Management of antiretroviral-drug resistance in HIV-infectedchildren is a global health concern. We compared the long-term virological outcomes of two cohorts of children living in a rural setting of South Africa. The first cohort initiated treatment before one year and the second after two years of age. The aim of this study was to describe the long-term consequences of early treatment initiation in terms of viral load and drug-resistance. METHODS: This retrospective study was conducted at the Edendale Hospital located in a peri-urban area of KwaZulu-Natal. Children were included during their planned appointment. Drug resistance was assessed genotypically on proviral DNA. RESULTS: From the 161 children included in this study, 93 samples were successfully genotyped. Both cohorts had comparable viral loads, but children treated early more often presented NRTI or NNRTI mutations, while there was no difference for PI mutations rates. CONCLUSIONS: Treatment was highly effective when comparing virological outcomes in both early- and late-treated cohorts. The persistence of NNRTI mutations could lead to treatment failures in children older than 3 years initiating their therapy with a NNRTI, or for those switching from a PI to NNRTI based regimen. The accumulation of NRTI mutations may lead to a functional PI monotherapy and consequently to viral escape. To promote access to HIV genotyping in resource-limited settings is challenging but essential to avoid inappropriate therapy switches in case of virological failure, and to adapt national treatment guidelines in line with the epidemiology of resistance.