Rilpivirine resistance and the dangerous liaisons with substitutions at position 184 among patients infected with HIV-1: analysis from a national drug-resistance database (ARCA).
Rilpivirine (RPV) is a novel NNRTI with a mutational pattern different from first-generation drugs of the same class: 16 resistance-associated mutations (RAM) are listed, but the combination E138K + M184I seems to be the most important. Aims of the present study were to evaluate the prevalence of these RAMs in Italian HIV-1 infected patients and to assess if previous drug history could represent a risk to develop RPV-related RAMs. The analysis was performed using the ARCA database, which contains data on resistance and therapy from subjects throughout Italy. Prevalence of RPV-associated and first-generation NNRTI-associated RAMs was evaluated. Linear regression model, odds ratio and 95% Confidence Interval were used to assess factors associated with the development of RPV RAMs, substitutions at position 184 and their combinations. A total of 8,067 tests were selected within the database. In Italian HIV-positive HAART-naïve patients, prevalence of the main RAMs for RPV is low except for E138A (present in 5.1% of subjects). The combination E138K + M184I is absent in both naïve and experienced subjects. A previous exposure to NVP might increase the risk to develop RPV-associated RAMs. TDF, EFV, and possibly FTC may predispose to the selection for M184I. Among Italian patients the susceptibility to RPV is widespread since some severe substitutions (e.g., E138K are rare), whereas issues exist for others (i.e., E138A, Y181C) which are more frequent. Appropriate use of RPV within a therapeutic sequencing might be controversial.
Department of Infectious Diseases, "Niguarda Cà Granda" Hospital, Milan, Italy.
Roberto
R
Rossotti
Luigi
L
Fonte
Genny
G
Meini
Franco
F
Maggiolo
Maurizio
M
Zazzi
Stefano
S
Rusconi
D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D003430:Cross-Sectional Studies; D019992:Databases as Topic; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D015995:Prevalence; D011743:Pyrimidines / Q000494:pharmacology*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D000068696:Rilpivirine
D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine
HIV-1; NNRTI-related mutations; rilpivirine; transmitted drug-resistance mutations