Open AccessFive‐year follow up of genotypic resistance patterns in HIV‐1 subtype C infected patients in Botswana after failure of thymidine analogue‐based regimens
Author(s) -
DouallaBell Florence,
Gaolathe Tendani,
Avalos Ava,
Cloutier Suzanne,
Ndwapi Ndwapi,
Holcroft Christina,
Moffat Howard,
Dickinson Diana,
Essex Max,
Wainberg Mark A,
Mine Madisa
Publication year - 2009
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.1186/1758-2652-12-25
Subject(s) - stavudine , didanosine , lamivudine , medicine , zidovudine , genotype , reverse transcriptase inhibitor , resistance mutation , regimen , nevirapine , reverse transcriptase , virology , gastroenterology , human immunodeficiency virus (hiv) , viral load , biology , virus , genetics , antiretroviral therapy , viral disease , polymerase chain reaction , hepatitis b virus , gene
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.