P24-19. Prevalence of ARV resistance in Ugandan children, at treatment start and after six months of treatment

Sandra Soeria-Atmadja [1], Pauline Amuge [2], Johanna Rubin[1], Jaran Erikssen [3], Sarah Nanzigu [4], Adeodata Kekitiinwa [2] , Celestino Obua [5], Lars L Gustafsson [3], Lars Navér[1]
Affiliates: [1] Clinical Science, Intervention and Technology, Karolinska Institutet, [2] Baylor College of Medicine Childrens Foundation Uganda, [3] Department of Laboratory Science, Division of Clinical Pharmacology, Karolinska Institutet, [4] Department of Clinical Pharmacology, Makerere University College of Health Sciences, [5] Mbarara University of science and technology.

Background
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.

Methods
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.

Results
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.

Conclusion
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