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Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort

Sureshnee Pillay1, Ruth M Bland12, Richard J Lessells13, Justen Manasa1, Tulio de Oliveira14 and Sivapragashini Danaviah15*

Author Affiliations

1 Africa Centre for Health and Population Studies, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

2 Royal Hospital for Sick Children, Glasgow, UK

3 Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK

4 Research Department of Infection, University College of London (UCL), London, UK

5 Rm 135, 1st Floor, DDMRI, 719 Umbilo Road, Congella 4013, South Africa

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AIDS Research and Therapy 2014, 11:3  doi:10.1186/1742-6405-11-3

Published: 20 January 2014

Abstract

Background

Better understanding of drug resistance patterns in HIV-infected children on antiretroviral therapy (ART) is required to inform public health policies in high prevalence settings. The aim of this study was to characterise the acquired drug resistance in HIV-infected children failing first-line ART in a decentralised rural HIV programme.

Methods

Plasma samples were collected from 101 paediatric patients (≤15 yrs of age) identified as failing ART. RNA was extracted from the plasma, reverse transcribed and a 1.3 kb region of the pol gene was amplified and sequenced using Sanger sequencing protocols. Sequences were edited in Geneious and drug resistance mutations were identified using the RegaDB and the Stanford resistance algorithms. The prevalence and frequency of mutations were analysed together with selected clinical and demographic data in STATA v11.

Results

A total of 101 children were enrolled and 89 (88%) were successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the time of genotyping. The majority of patients on an NNRTI regimen (80%) had both nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 30.1% had one or more thymidine analogue mutation (TAM) and 6% had ≥3 TAMs. Only one child on a PI-based regimen harboured a major PI resistance mutation.

Conclusions

Whilst the patterns of resistance were largely predictable, the few complex resistance patterns seen with NNRTI-based regimens and the absence of major PI mutations in children failing PI-based regimens suggest the need for wider access to genotypic resistance testing in this setting.