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Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population
Thesis (MSc)--Stellenbosch University, 2012.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2012
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| _version_ | 1867613933289865216 |
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| access_status_str | Open Access |
| author | Maseko Phiri, Thabiso |
| author2 | Smith, Carine |
| author_browse | Maseko Phiri, Thabiso Smith, Carine |
| author_facet | Smith, Carine Maseko Phiri, Thabiso |
| author_sort | Maseko Phiri, Thabiso |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2012. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/71845 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:44:01Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2012 |
| publishDateRange | 2012 |
| publishDateSort | 2012 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/71845 Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population Maseko Phiri, Thabiso Smith, Carine Smith, Rob Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Antiretroviral therapy (ART) HIV infections -- Genetic aspects -- Zambia Drug resistance geno-typing Theses -- Physiology Dissertations -- Physiology Thesis (MSc)--Stellenbosch University, 2012. 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. 2012-11-02T10:19:42Z 2012-12-12T08:14:04Z 2012-11-02T10:19:42Z 2012-12-12T08:14:04Z 2012-12 Thesis http://hdl.handle.net/10019.1/71845 en_ZA Stellenbosch University vii, 128 p. : ill. (some col.) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Antiretroviral therapy (ART) HIV infections -- Genetic aspects -- Zambia Drug resistance geno-typing Theses -- Physiology Dissertations -- Physiology Maseko Phiri, Thabiso Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title | Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title_full | Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title_fullStr | Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title_full_unstemmed | Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title_short | Predictive value of gene mutations as a diagnostic tool for ART resistance in a Zambian population |
| title_sort | predictive value of gene mutations as a diagnostic tool for art resistance in a zambian population |
| topic | Antiretroviral therapy (ART) HIV infections -- Genetic aspects -- Zambia Drug resistance geno-typing Theses -- Physiology Dissertations -- Physiology |
| url | http://hdl.handle.net/10019.1/71845 |
| work_keys_str_mv | AT masekophirithabiso predictivevalueofgenemutationsasadiagnostictoolforartresistanceinazambianpopulation |