{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:35:53Z","timestamp":1777451753861,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We aimed to characterize the molecular epidemiology of HIV type-1 (HIV-1) and the prevalence of drug- associated mutations prior to initiating highly active antiretroviral therapy (HAART) in the Free State province, South Africa. The Free State has a population of 3 million, an antenatal HIV prevalence of approximately 34% and a well established infrastucture for antiretroviral (ARV) provision.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HIV-1 polymerase genes were sequenced from 425 HAART-naive HIV-1-positive patients at voluntary primary healthcare HIV testing centres, who were subsequently attending district centres for assessment for commencing ARVs. Patients (&gt;18 years) were sampled randomly with no exclusion for gender or clinical criteria. Sequences were analysed according to phylogeny and drug resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phylogenetic clustering within the cohort was suggestive of multiple introductions of subtype C virus into the region. Drug resistance mutations (according to the International AIDS Society-USA classification) were distributed randomly across the cohort phylogeny with an overall prevalence of 2.3% in the sampled patients. When stratified according to CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count, the prevalence of resistance was 3.6%, 0.9% and 1.2% for CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts &lt;100, 200-350 and &gt;500 cells\/\u03bc l, respectively, and was most common for non-nucleoside reverse transcriptase inhibitor resistance (3.1% in patients with CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count &lt;100 cells\/\u03bc l). We surveyed all drug-selected mutations and found further significant clustering among patients with low CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts ( P=0.003), suggesting unrecognized exposure to ARVs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In the Free State population, there was a statistical association between low CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts and drug-associated viral polymorphisms. Our data advocate the benefit of detailed history taking from patients starting HAART at low CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts with close follow-up of the virological response.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp1416","type":"journal-article","created":{"date-parts":[[2009,11,11]],"date-time":"2009-11-11T12:18:00Z","timestamp":1257941880000},"page":"975-984","source":"Crossref","is-referenced-by-count":21,"title":["Prevalence of HIV type-1 drug-associated mutations in pre-therapy patients in the Free State, South Africa"],"prefix":"10.1177","volume":"14","author":[{"given":"Kuan-Hsiang Gary","family":"Huang","sequence":"first","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK"},{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Goedhals","sequence":"additional","affiliation":[{"name":"University of the Free State, Bloemfontein, South Africa"},{"name":"National Health Laboratory Services (NHLS), Bloemfontein, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Fryer","sequence":"additional","affiliation":[{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"},{"name":"Department of Zoology, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cloete","family":"van Vuuren","sequence":"additional","affiliation":[{"name":"University of the Free State, Bloemfontein, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aris","family":"Katzourakis","sequence":"additional","affiliation":[{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"},{"name":"Department of Zoology, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tulio De","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Africa Centre for Health and Population Studies, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, KwaZulu-Natal, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Brown","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK"},{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Cassol","sequence":"additional","affiliation":[{"name":"Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Seebregts","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Research Division, Medical Research Council, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"McLean","sequence":"additional","affiliation":[{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"},{"name":"Department of Zoology, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK"},{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney","family":"Phillips","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK"},{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Frater","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, Oxford University, Oxford, UK"},{"name":"Institute for Emergent Infections of Humans, James Martin 21st Century School, Oxford University, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Bloemfontein-Oxford Collaborative Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2009,10,1]]},"reference":[{"key":"bibr1-IMP1416","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31802bf109"},{"key":"bibr2-IMP1416","unstructured":"Department of Health (South Africa). Operational plan for comprehensive HIV and Aids care, management and treatment for South Africa, 19 November 2003. (Accessed 19 March 2009.) Available from http:\/\/www.hst.org.za\/uploads\/files\/aidsplan.pdf."},{"key":"bibr3-IMP1416","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199803263381301"},{"key":"bibr4-IMP1416","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200205240-00007"},{"key":"bibr5-IMP1416","first-page":"1","volume":"156","author":"Shekelle P.","year":"2007","journal-title":"Evid Rep Technol Assess (Full Rep)"},{"key":"bibr6-IMP1416","doi-asserted-by":"publisher","DOI":"10.1089\/088922202753747950"},{"key":"bibr7-IMP1416","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2006.22.1306"},{"key":"bibr8-IMP1416","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.4.2587-2599.2003"},{"key":"bibr9-IMP1416","unstructured":"Dorrington R.E., Bradshaw D., Johnson L., Daniel T. The demographic impact of HIV\/AIDS in South Africa: national and provincial indicators for 2006. Cape Town: Centre for Acturial Research, South African Medical Research Council, Actuarial Society of South Africa 2006; pp. 1\u2013116."},{"key":"bibr10-IMP1416","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2007.10"},{"key":"bibr11-IMP1416","first-page":"138","volume":"16","author":"Johnson V.A.","year":"2008","journal-title":"Top HIV Med"},{"key":"bibr12-IMP1416","unstructured":"Stanford University. HIV drug resistance database. (Accessed 19 March 2009.) Available from http:\/\/hivdb.stanford.edu\/."},{"key":"bibr13-IMP1416","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328011e691"},{"key":"bibr14-IMP1416","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004724"},{"key":"bibr15-IMP1416","unstructured":"World Health Organization. Team HIV Drug Resistance Surveillance. Guidelines for surveillance of HIV drug resistance 2003. (Accessed 19 March 2009.) Available from www.who.int\/3by5\/publications\/guidelines\/en\/execsumm.pdf."},{"key":"bibr16-IMP1416","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69158-7"},{"key":"bibr17-IMP1416","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn374"},{"key":"bibr18-IMP1416","unstructured":"Seebregts C.J., van Vuuren C., Goedhals D. Baseline characterization and resistance genotyping of HIV from the public sector antiretroviral treatment program in the Free State Province of South Africa.\n                      3rd South African AIDS Conference\n                      . 5\u20138 June 2007, Durban, South Africa. Poster 743."},{"key":"bibr19-IMP1416","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00022-07"},{"key":"bibr20-IMP1416","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti607"},{"key":"bibr21-IMP1416","unstructured":"de Oliveira T., Cassol S. South African National Bioinformatics Institute. BioAfrica, HIV bioinformatics in Africa. (Accessed 13 March 2009.) Available from http:\/\/www.bioafrica.net."},{"key":"bibr22-IMP1416","doi-asserted-by":"publisher","DOI":"10.1080\/10635150390235520"},{"key":"bibr23-IMP1416","unstructured":"Los Alamos National Laboratory. HIV Databases 2007. (Accessed 19 March 2009.) Available from www.hiv.lanl.gov\/content\/index."},{"key":"bibr24-IMP1416","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00889-07"},{"key":"bibr25-IMP1416","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1177\/135965350801302S04","volume":"13","author":"Bennett D.E.","year":"2008","journal-title":"Antivir Ther"},{"key":"bibr26-IMP1416","doi-asserted-by":"publisher","DOI":"10.1086\/426592"},{"key":"bibr27-IMP1416","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm159"},{"key":"bibr28-IMP1416","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000131310.52526.c7"},{"key":"bibr29-IMP1416","unstructured":"Wallis C., Bell C., Boulme R. Emerging ART drug resistance in subtype C: experience from 2 clinics in Johannesburg, South Africa.\n                      14th Conference on Retroviruses and Opportunistic Infections\n                      . 25\u201328 February 2007, Los Angeles, CA, USA. Poster 661."},{"key":"bibr30-IMP1416","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041305"},{"key":"bibr31-IMP1416","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200404090-00008"},{"key":"bibr32-IMP1416","unstructured":"Uy J., Armon C., Buchacz K., Brooks J., Investigators H. Initiation of HAART at CD4 cell counts \u2265350 cells\/mm\n                      3\n                      is associated with a lower prevalence of antiretroviral resistance mutations at virologic failure.\n                      4th IAS Conference on HIV Pathogenesis, Treatment and Prevention\n                      . 22\u201325 July 2007, Sydney, Australia. Abstract WEPEB017."},{"key":"bibr33-IMP1416","doi-asserted-by":"publisher","DOI":"10.1086\/427212"},{"key":"bibr34-IMP1416","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-8-63"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1416","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:49:09Z","timestamp":1777380549000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,10]]}},"alternative-id":["10.3851\/IMP1416"],"URL":"https:\/\/doi.org\/10.3851\/imp1416","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10]]}}}