Evolution and predictors of HIV type-1 drug resistance in patients failing combination antiretroviral therapy in Italy.
BACKGROUND
This study aimed to examine the evolution of genotypic drug resistance prevalence in treatment-failing patients in the multicentre, Italian, Antiretroviral Resistance Cohort Analysis (ARCA).


METHODS
Patients with a drug resistance genotype test performed between 1999 and 2006 at failure of a combination antiretroviral therapy and with complete treatment history were selected. The prevalence of resistance was measured overall, per calendar year, per drug class and per treatment line at failure.


RESULTS
The overall resistance prevalence was 81%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) declined after 2002 (68% in 2006; chi(2) for trend P=0.004); resistance to non-NRTIs (NNRTIs) stabilized after 2004; and resistance to protease inhibitors (PIs) declined after 2001 (43% in 2006; P=0.004). In first-line failures, NRTI resistance decreased after 2002 (P=0.006), NNRTI resistance decreased after 2003 (P=0.001) and PI resistance decreased after 2001 (P<0.001). Independent predictors of resistance to any class were HIV type-1 transmission by heterosexual contacts as compared with injecting drug use, a higher number of experienced regimens, prior history of suboptimal therapy, higher viral load and CD4+ T-cell counts, more recent calendar year and viral subtype B carriage, whereas the use of PI-based versus NNRTI-based regimens at failure was associated with a reduced risk of resistance. There was an increase of type-1 thymidine analogue and of protease mutations L33F, I47A/V, I50V and I54L/M, whereas L90M decreased over calendar years.


CONCLUSIONS
During more recent years, emerging drug resistance has decreased, particularly in first-line failures. The prevalence continues to be high in multiregimen-failing patients.
Di Giambenedetto
Simona
S
Institute of Clinical Infectious Diseases, Catholic University, Rome, Italy. simona.digiambenedetto@rm.unicatt.it
Zazzi
Maurizio
M
Corsi
Paola
P
Gonnelli
Angela
A
Di Pietro
Massimo
M
Giacometti
Andrea
A
Almi
Paolo
P
Trezzi
Michele
M
Boeri
Enzo
E
Gianotti
Nicola
N
Menzo
Stefano
S
Del Gobbo
Romana
R
Francisci
Daniela
D
Nerli
Alessandro
A
Galli
Luisa
L
De Luca
Andrea
A
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D020010:Heterosexuality; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D012307:Risk Factors; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D016333:HIV Protease