Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population
Date
2012-12
Authors
Maseko Phiri, Thabiso
Journal Title
Journal ISSN
Volume Title
Publisher
Stellenbosch : Stellenbosch University
Abstract
Background: While Selection of reverse transcriptase (RT) mutation has been
reported frequently, protease (PR) mutations on antiretroviral therapy (ART) including
boosted Protease inhibitor (PI) have not been reported as much in Zambia. Affordable
in-house genotyping assays can been used to expand the number of patients receiving
drug resistance geno-typing, which can aid in determining prevalence of RT/PI
emerging mutations.
Methods: A previously published drug resistance genotyping assay was modified and
used to genotype RT and PR genes. 19 patients virologically failing first-line regimen
and 24 failing second-line regimen were studied to determine resistance patterns.
Virological failure was defined as failing to maintain <1000 copies/mL during ART.
Only major and minor RT and PR mutations (IAS-USA 2010) were considered for
analysis. The in-house assay was validated by comparing sequence data of 7 previously
ViroSeq tested samples and 5 randomly selected samples to determine reproducibility.
Results: The in-house assay efficiently amplified all 12 validation samples with the
lowest sample scoring 99.4% sequence homology. The most common RT mutation was
M184V (79% n=19) and (71% n=24) first and second-line respectively. No significant
differences were reported in all the other RT mutations between first-line and secondline
regimens. Drug resistant PI mutations (I54V, M46I and V82A all present 20.8%)
were only found in the second-line regimen and were insignificant, p= 0.0562.
Conclusion: The in-house assays can be used as alternatives for commercial kits to
genotype HIV-1C in Zambia without compromising test quality. The insignificant PI
drug resistant mutations which were found, despite virological failure in patients, could
indicate a possibility of other mutations within the HIV-1 genome that could reduce PI
susceptibility.
Description
Thesis (MSc)--Stellenbosch University, 2012.
Keywords
Antiretroviral therapy (ART), HIV infections -- Genetic aspects -- Zambia, Drug resistance geno-typing, Theses -- Physiology, Dissertations -- Physiology