''Descriptive study of HIV drug resistance genotype testing in a public sector paediatric population in Johannesburg"

Ngabire, Phocas
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The introduction of combined antiretroviral treatment (cART) reduced HIV related mortality more than 70% and the rate of new infection in children continue to decrease considerably. However this benefit is threatened by the emergence of drug resistant strains of HIV. Studies exploring the patterns of drug resistance in the paediatric population are crucial for policy makers and for individual patients’ management. In sub-Saharan Africa where HIV-1 subtype C is more prevalent, there is a limited number of paediatric studies exploring the drug resistance patterns. To get more insight on this problem, we explored the drug resistance mutations (DRMs) patterns in a paediatric population attending a referral public paediatric HIV clinic. Methodology The study was a cross-sectional retrospective descriptive study. Convenience sampling method was used and all paediatric patients (0-14 years) who underwent genotypic HIV drug resistance testing at Empilweni Clinic between January 1st, 2004 and February 28th, 2012 were included. Demographic and clinical data were collected from the clinical electronic database and DRM frequencies related to treatment exposure were presented. Results During our study period, 63 patient samples were sent for HIV genotyping drug resistance testing. Eleven samples did not meet the inclusion criteria. Among the 52 patient samples retained, 44 patients (84.6%) had a successful HIV amplification and all were infected with HIV-1 subtype C. Ninety one percent (n=40) of the patients had at least one DRM isolated but in only 78% (n=34) did these mutations translate into genotypic drug resistance to at least one antiretroviral drug (ARV) used in South Africa. Nucleotide reverse transcriptase inhibitors (NRTI) mutations were the most commonly identified with M184V being the most prevalent (64.4%; n=29). This was associated with thymidine analogue mutations (TAMs) in 36.3% of the patients (n=16). TAMs were identified in 25% (n=11) of the patients. K65R and Q151M were rarely identified in our cohort. V106M and K103N were the most common non-nucleotide reverse transcriptase inhibitors (NNRTI) mutations and were both identified in 21.9% (n=7) of the patients exposed to NNRTI-based regimen. V82A was the most commonly identified protease gene (PR) mutation in 29.3% (n=12) of the cases. Forty eight percent of the patients (n=21) had a dual class resistance and 11.4% (n=5) had resistance to ARVs from all the three classes. Over a quarter (27.2%, n=12) of the patients in our cohort were still sensitive to all ARVs used in South Africa. The development of drug resistance was not associated with any clinical characteristic in our cohort. Conclusion The drug resistance mutations identified in paediatric patients failing cART show a complex pattern with some failing patients still sensitive to all ARVs while others harbour complex resistance mutations. Therefore, regular counselling to optimize adherence and regular viral load monitoring for early detection of failure may be important tools for continued cART success. Given the complexity of the DRMs patterns in paediatric patients, the HIV drug resistance test is warranted to guide the choice of appropriate cART regimens.
A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the field of Paediatrics. Johannesburg, 2015