Five-Year Follow Up of Genotypic Resistance Patterns in HIV-1 Subtype C Infected Patients in Botswana after Failure of Thymidine Analogue-Based Regimens

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Five-Year Follow Up of Genotypic Resistance Patterns in HIV-1 Subtype C Infected Patients in Botswana after Failure of Thymidine Analogue-Based Regimens

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Title: Five-Year Follow Up of Genotypic Resistance Patterns in HIV-1 Subtype C Infected Patients in Botswana after Failure of Thymidine Analogue-Based Regimens
Author: Doualla-Bell, Florence; Avalos, Ava; Cloutier, Suzanne; Ndwapi, Ndwapi; Holcroft, Christina; Moffat, Howard; Dickinson, Diana; Essex, Max; Wainberg, Mark A; Mine, Madisa; Gaolathe, Tendani

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Citation: Doualla-Bell, Florence, Tendani Gaolathe, Ava Avalos, Suzanne Cloutier, Ndwapi Ndwapi, Christina Holcroft, Howard Moffat, et al. 2009. Five-year follow up of genotypic resistance patterns in HIV-1 subtype C infected patients in Botswana after failure of thymidine analogue-based regimens. Journal of the International AIDS Society 12:25.
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Abstract: Objective: Our objective was to establish genotypic resistance profiles among the 4% of Batswana patients who experienced virologic failure while being followed within Botswana's National Antiretroviral Treatment Program between 2002 and 2007. Methods: At the beginning of the national program in 2002, almost all patients received stavudine (d4T), together with didanosine (ddI), as part of their first nucleoside reverse transcriptase inhibitor (NRTI)-based regimen (Group 1). In contrast, the standard of care for all patients subsequently enrolled (2002-2007) included zidovudine/lamivudine (ZDV/3TC) (Group 2). Genotypes were analyzed in 26 patients from Group 1 and 37 patients from Group 2. Associations between mutations were determined using Pearson's correlation coefficient and Jaccard's coefficient of similarity. Results: Seventy-eight percent of genotyped patients possessed mutations associated with protease inhibitor (PI) resistance while 87% and 90%, respectively, exhibited mutations associated with NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The most frequent PI mutations involving resistance to NFV were L90M (25.2%) and D30N (16.2%), but mutations at positions K45Q and D30N were often observed in tandem (P = 60.5, J = 50; p = 0.002; Group 2) alongside Q61E in 42.8% of patients who received ZDV/3TC. Both major patterns of thymidine analogue mutations, TAM 1 (48%) and TAM 2 (59%), were represented in patients from Group 1 and 2, although M184V was higher among individuals who had initially received ddI (61% versus 40.5%). In contrast, L74V was more frequent among individuals from Group 2 (16.2% versus 7.7%). Differences in regard to NNRTI mutations were also observed between Group 1 and Group 2 patients. Conclusion: Despite a low rate of therapeutic failure (4%) among these patients, those who failed possessed high numbers of resistance mutations as well as novel resistance mutations and/or polymorphisms at sites within reverse transcriptase and protease.
Published Version: doi:10.1186/1758-2652-12-25
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2770537/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4551788
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