TY - JOUR
T1 - Genotypic HIV-1 Drug Resistance among Patients Failing Tenofovir-Based First-Line HAART in South India
AU - Dinesha, Thongadi Ramesh
AU - Gomathi, Selvamurthi
AU - Boobalan, Jayaseelan
AU - Sivamalar, Sathasivam
AU - Solomon, Sunil S.
AU - Pradeep, Ambrose
AU - Poongulali, Selvamuthu
AU - Solomon, Suniti
AU - Balakrishnan, Pachamuthu
AU - Saravanan, Shanmugam
N1 - Publisher Copyright:
© Copyright 2016, Mary Ann Liebert, Inc. 2016.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.
AB - According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.
KW - K65R
KW - NRTI
KW - TDF
KW - first-line
KW - immunological failure
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U2 - 10.1089/aid.2016.0110
DO - 10.1089/aid.2016.0110
M3 - Article
C2 - 27334566
AN - SCOPUS:85006010327
SN - 0889-2229
VL - 32
SP - 1234
EP - 1236
JO - AIDS research and human retroviruses
JF - AIDS research and human retroviruses
IS - 12
ER -