Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir.
The mutation RT-K65R confers resistance to tenofovir (TDF). Although its prevalence is increasing with the use of this drug, clinical and genotypic correlates of K65R occurrence have yet to be fully identified. Clinical, virological and immunological and genotypic data of patients naïve for TDF who failed HAART regimens and underwent genotypic resistance test (GRT) during 1999-2003 were collected in a database and analyzed retrospectively. Out of 1392 GRT performed for 771 patients, 12 TDF-naïve patients had the K65R mutation with an overall prevalence of 1.6%. Previous AIDS, the use of abacavir, and treatment with efavirenz at GRT were independently associated with a greater risk of expressing K65R, while patients with longer exposure to lamivudine were less likely to present the mutation. Among genotypic correlates, the presence of M184V and NAMs seems to be protective for the emergence of K65R, while a strong positive correlation was found with the Q151M complex mutation. Moreover, the L100I mutation was independently associated with a higher probability of presenting K65R. The selection of mutation K65R in patients failing without TDF is rare. However, exposure to abacavir and/or efavirenz, presence of Q151M and/or L100I, and prior AIDS may favor the selection of this mutation. Conversely, long 3TC exposure, and the presence of M184V or NAMs seem to be protective.
Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy. trotta@inmi.it
Maria Paola
MP
Trotta
Sandro
S
Bonfigli
Francesca
F
Ceccherini-Silberstein
Rita
R
Bellagamba
Roberta
R
D'Arrigo
Fabio
F
Soldani
Mauro
M
Zaccarelli
Maria
M
Concetta Bellocchi
Patrizia
P
Lorenzini
Patrizia
P
Marconi
Evangelo
E
Boumis
Federica
F
Forbici
Ubaldo Visco
UV
Comandini
Valerio
V
Tozzi
Pasquale
P
Narciso
Carlo
C
Federico Perno
Andrea
A
Antinori
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068698:Tenofovir; D017211:Treatment Failure
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine