Analysis of selection pressure and mutational pattern of HIV type 1 reverse transcriptase region among treated and nontreated patients.
Variation of the HIV-1 subtype C reverse transcriptase region (RT) resulting in response to the selective pressures of drug therapy remains poorly characterized. Here, we compared the genetic variation resulting in the presence and absence of antiretroviral drug selective pressures on HIV-1 subtype C RT among nontreated and treated patients. The nucleotide variability, nonsynonymous and synonymous ratio, and the positively selected mutations were determined by comparing the RT sequences isolated at two time points among nontreated (baseline and follow-up) and treated patients (baseline and treatment failure). Compared to the nontreated patients, the intrapatient nucleotide variability, the number of nonsynonymous and synonymous substitutions was significantly higher among the treated patients. Among the mutations positively selected, the frequency of D121Y, I135R, and Q207E increased and the frequency of mutation S48T decreased significantly during treatment failure. Further studies are essential to discover the role of these mutations during treatment in HIV-1 subtype C.
Shanmugasundaram
Uma
U
YRG Centre for AIDS Research and Education (YRG CARE), Voluntary Health Services Hospital Campus, Taramani, Chennai, India.
Solomon
Suniti
S
Madhavan
Vidya
V
Kailapuri
Murugavel G
MG
Nagalingeswaran
Kumarasamy
K
Solomon
Sunil Suhas
SS
Mayer
Kenneth H
KH
Pachamuthu
Balakrishnan
B
D000328:Adult; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012641:Selection, Genetic
D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase