The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir.
OBJECTIVE
The overall prevalence of the K65R mutation in HIV-1 reverse transcriptase has increased in treatment-experienced patients, mostly attributed to the increasing use of tenofovir (TDF). A number of TDF-based regimens are associated with high rate of early virological failure. In this study, we evaluated the impact of these combinations on K65R selection over time.


METHODS
Treatment-experienced patients who had a genotypic resistance test at time of failure in the period 2002-2005 in a hospital in Lisbon were included. Incidence of K65R was calculated and compared with proportions of failing therapies in the respective year of sampling including TDF or didanosine plus stavudine and their respective frequency of K65R selection were analyzed using classical statistics and Bayesian Network Learning.


RESULTS
The overall rate of K65R in the database was consistent with earlier reports. The incidence of K65R increased in the period 2002-2004 but showed a sharp, significant decrease in 2005, despite a continuous increase of patients failing TDF-based regimens. The proportion of patients failing certain not-recommended regimens decreased sharply in 2005 and therefore correlated well with K65R incidence trend.


CONCLUSIONS
This study suggests that the use of certain TDF-based regimens caused the increase in K65R incidence over the last years.
Theys
Kristof
K
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium. kristof.theys@uz.kuleuven.ac.be
Vercauteren
Jurgen
J
Abecasis
Ana B
AB
Libin
Pieter
P
Deforche
Koen
K
Vandamme
Anne-Mieke
AM
Camacho
Ricardo
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001499:Bayes Theorem; D003627:Data Interpretation, Statistical; D030561:Databases, Nucleic Acid; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D011174:Portugal / Q000453:epidemiology; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000225:Adenine