{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:42:25Z","timestamp":1787805745903,"version":"build-2784847793"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher\u2019s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation.<\/jats:p>","DOI":"10.3390\/v9110330","type":"journal-article","created":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T12:38:48Z","timestamp":1510144728000},"page":"330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals"],"prefix":"10.3390","volume":"9","author":[{"given":"Sinaye","family":"Ngcapu","sequence":"first","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"},{"name":"Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0242-7000","authenticated-orcid":false,"given":"Kristof","family":"Theys","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven\u2013University of Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-758X","authenticated-orcid":false,"given":"Pieter","family":"Libin","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven\u2013University of Leuven, 3000 Leuven, Belgium"},{"name":"Artificial Intelligence Lab, Department of Computer Science, Vrije Universiteit Brussel, Brussels, 1050 Elsene, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Marconi","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Sunpath","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-3992","authenticated-orcid":false,"given":"Thumbi","family":"Ndung\u2019u","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"},{"name":"Africa Health Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"},{"name":"Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA 01239, USA"},{"name":"Max Planck Institute for Infection Biology, Chariteplatz, D-10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Gordon","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,8]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2017, June 07). 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