Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive patient.
The purpose of our study was to examine the emergence of the Y181C resistance mutation in an NNRTI-naive subject (index patient) at different time points. Phylogenetic trees in protease (PR) and partial reverse transcriptase (RT) regions were inferred by the maximum likelihood (ML) method. The Y181C mutation was detected for the first time when the patient was receiving d4T + ddI + LPV/r; the previous drug combination was 3TC + AZT + IDV. The particular mutation (Y181C) was not present at any time point during the treatment period with 3TC + AZT + IDV. Moreover, there was no evidence of resistance mutations in RT before the initiation of antiretroviral therapy. Phylogenetic analysis including sequences from the index patient and his spouse sampled at different time points, as well as control sequences belonging to the same HIV-1 subtype, revealed that there is no evidence of coinfection or reinfection with Y181C resistance strains, while the virus for both subjects was classified as subtype CRF14_BG. Overall, our findings suggest that the Y181C resistance mutation may be selected, not only by NNRTIs, but also by d4T. This may be of particular significance in developing countries where treatment with Triomune, a fixed combination of d4T, ddI, and nevirapine, is common. The genetic barrier against resistance of this combination may be lower than previously thought.
Magiorkinis
Emmanouil
E
Department of Hygiene and Epidemiology, University of Athens Medical School, GR-11527 Athens, Greece.
Paraskevis
Dimitrios
D
Sambatakou
Helen
H
Gargalianos
Panagiotis
P
Haida
Caterina
C
Vassilakis
Alexandros
A
Hatzakis
Angelos
A
D019943:Amino Acid Substitution / Q000235:genetics*; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D020125:Mutation, Missense; D010802:Phylogeny; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1