Antiretroviral resistance patterns and factors associated with resistance in adult patients failing NNRTI-based regimens in the western cape, South Africa

Date
2011
Authors
van Zyl G.U.
van der Merwe L.
Claassen M.
Zeier M.
Preiser W.
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Abstract
Antiretroviral drug resistance in patients failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line combination antiretroviral treatment (ART) is influenced by: regimen choice, HIV-1 subtype, detection of and response to therapy failure. In order to describe resistance patterns by genotypic testing, at the time of first-line ART failure and to describe associations with having M184I/V, K65R, three or more thymidine analog mutations (TAMs) and etravirine (ETV) resistance, the prevalence of antiretroviral drug resistance associated mutations in a cross-sectional study, at two South African public health clinic settings, at the time of virologic failure (HIV-1 RNA load >400copies/ml) are described. Also reported are associations of therapy choice, prolonged virologic failure, and concurrent HIV viral load and CD4 count with the presence of M184I/V, TAMs, K65R, and resistance to ETV. Of 167 adult patients with virologic failure on first-line ART, 28 (17%) had no resistance, 137 (82%) had NNRTI resistance, 101 (60%) M184I/V, 20 (12%) TAMs, of which 4 had 3 or more TAMs, and 7 (4%) had K65R, of which 6 were on D4T and one on AZT. A prolonged estimated period of failure was associated with having ≥3 TAMs. Patients treated with nevirapine (NVP) were more likely to have ETV resistance than those treated with efavirenz (EFV). Major protease inhibitor mutations were not detected. A delayed response to ART failure may risk accumulation of TAMs in patients on an NNRTI-based regimen. The use of NVP rather than EFV was associated with ETV resistance. © 2011 Wiley-Liss, Inc..
Description
Keywords
Antiretroviral drug resistance, Etravirine associated mutations, HIV-1 subtype C, Nevirapine, Thymidine analog mutations, CD4 antigen, efavirenz, etravirine, lamivudine, nevirapine, nonnucleoside reverse transcriptase inhibitor, stavudine, tenofovir, thymidine, virus RNA, zidovudine, adult, article, CD4 lymphocyte count, cross resistance, cross-sectional study, female, genotype, highly active antiretroviral therapy, human, Human immunodeficiency virus 1, Human immunodeficiency virus 1 infection, major clinical study, male, nonhuman, South Africa, treatment failure, virus load, virus mutation, virus resistance, virus strain
Citation
Journal of Medical Virology
83
10
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