Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population

dc.contributor.advisorSmith, Carineen_ZA
dc.contributor.advisorSmith, Roben_ZA
dc.contributor.authorMaseko Phiri, Thabisoen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Physiological Sciences.en_ZA
dc.descriptionThesis (MSc)--Stellenbosch University, 2012.en_ZA
dc.description.abstractBackground: 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.en_ZA
dc.format.extentvii, 128 p. : ill. (some col.)
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.subjectAntiretroviral therapy (ART)en_ZA
dc.subjectHIV infections -- Genetic aspects -- Zambiaen_ZA
dc.subjectDrug resistance geno-typingen_ZA
dc.subjectTheses -- Physiologyen_ZA
dc.subjectDissertations -- Physiologyen_ZA
dc.titlePredictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian populationen_ZA
dc.rights.holderStellenbosch Universityen_ZA

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