Impact of Fixed-Dose Combinations of Antiretrovirals on Prevalence Trends of HIV Resistance: A 7 Year Follow-Up Study

Objectives: To determine the effectiveness of the introduction of fixed-dose combinations of antiretrovirals (FDCAs) in reducing resistance, and to describe trends of resistance-associated mutations (RAMs) in relation to drug exposure and the risk factors associated with multi-class drug resistance (MCDR) in Catalonia (Spain). Methods: Observational prospective study of HIV Resistance in Catalonia from 2002 to 2008. We included 2,718 HIV+ patients (≥16 years of age) with virological failure (Viral Load>1000 copies/ml). Differences between the Pre-FDCAs period (2002-2005) and the Post-FDCAs period (2005-2008) were assessed by multivariate logistic regressions. Prevalence of resistances and exposure to ARVs. trends were also assessed by test of trend Results: We observed a downward trend from 2002 to 2008 in all class-resistance mutations and RAMS (p<0.0001). This trend coincides with a reduction in exposure to older ARVs., and with an increase in exposure to newer drugs. Multivariate analyses showed the Post-FDCAs period as an independent protective factor for the presence of any resistance, for MCDR, and for major mutations of reverse transcriptase and protease, with Odds Ratios (95% CI) between 0.32 (0.26-0.39) and 0.67 (0.51-0.86). Male sex, sexual transmission group, older age, duration of HIV infection, number of treatment failures and exposure to three-class drugs are also risk factors for the presence of MCDR. Conclusions: There was an important reduction of the risk of class-resistances, MCDR and RAMs in the Post- FDCAs period independently of others factors. Reductions in specific mutations are related to changes in antiretroviral use. These results support the use of FDCAs for the treatment of HIV infection.