Sandra Soeria-Atmadja , Pauline Amuge , Johanna Rubin, Jaran Erikssen , Sarah Nanzigu , Adeodata Kekitiinwa  , Celestino Obua , Lars L Gustafsson , Lars Navér
Affiliates:  Clinical Science, Intervention and Technology, Karolinska Institutet,  Baylor College of Medicine Childrens Foundation Uganda,  Department of Laboratory Science, Division of Clinical Pharmacology, Karolinska Institutet,  Department of Clinical Pharmacology, Makerere University College of Health Sciences,  Mbarara University of science and technology.
Pre-treatment HIV drug resistance is an emerging problem in Sub-Saharan Africa and children are particularly at risk, due to exposure to antiretroviral drugs used for prevention of mother-to-child transmission (PMTCT ). Recent studies indicate that the prevalence of pre-treatment HIV drug resistance is increasing also in newly diagnosed children without history of exposure to PMTCT.
109 HIV-positive, treatment naïve Ugandan children aged 3-12 years, were enrolled for a 24 weeks follow-up, after initiating efavirenz based therapy during 2015-2016. At baseline and after 24 weeks, viral load (VL) was assessed and genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTI) and nucleoside reverse transcriptase inhibitors (NRTI) was analysed if VL> 500 copies/mL. Self reported history of PMTCT exposure was recorded. Undetectable VL was defined as VL<40 copies/mL. Stanford algorithm (http://hivdb.stanford.edu/) was used to obtain drug resistance profiles.
Median age was 6 years at treatment start. Only 1/109 children reported exposure to PMTCT. 105/109 children had no or unknown PMTCT history and for 3 children there was no data. Baseline HIV drug resistance results were available in 95 cases and drug resistance associated mutations were detected in 19/95 (20%) children. 5/95 (5 %) had any NRTI mutations and 17/95 (18%) had any NNRTI mutations before treatment start. High level pre-treatment drug resistance against efavirenz and nevirapine was present in 7/95 (7%) respectively 10/95 (11%) of cases.
After 24 weeks 73/91 (80%) children had undetectable VL and 18/91 (20%) had VL above 40. In 11/12 children with VL exceeding 500 copies, NRTI and/or NNRTI associated mutations were detected. 10 children acquired new resistance mutations compared to baseline results.
In a treatment naïve group of Ugandan children aged 3-12 years, the prevalence of NRTI/NNRTI associated pre-treatment drug resistance was 20% eventhough the majority of children reported no or unknown history of PMTCT exposure. Eleven percent (10/91) acquired resistance mutations after six months of treatment