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