Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study

Abstract

To investigate the relationship between detection of HIV drug resistance by 2 years from starting antiretroviral therapy and the subsequent risk of progression to AIDS and death. Virological failure was defined as experiencing two consecutive viral loads of more than 400 copies/ml in the time window between 0.5 and 2 years from starting antiretroviral therapy (baseline). Patients were grouped according to evidence of virological failure and whether there was detection of the International AIDS Society resistance mutations to one, two or three drug classes in the time window. Standard survival analysis using Kaplan-Meier curves and Cox proportional hazards regression model with time-fixed covariates defined at baseline was employed. We studied 8229 patients in EuroSIDA who started antiretroviral therapy and who had at least 2 years of clinical follow-up. We observed 829 AIDS events and 571 deaths during 38,814 person-years of follow-up resulting in an overall incidence of new AIDS and death of 3.6 per 100 person-years of follow-up [95% confidence interval (CI):3.4-3.8]. By 96 months from baseline, the proportion of patients with a new AIDS diagnosis or death was 20.3% (95% CI:17.7-22.9) in patients with no evidence of virological failure and 53% (39.3-66.7) in those with virological failure and mutations to three drug classes (P = 0.0001). An almost two-fold difference in risk was confirmed in the multivariable analysis (adjusted relative hazard = 1.8, 95% CI:1.2-2.7, P = 0.005). Although this study shows an association between the detection of resistance at failure and risk of clinical progression, further research is needed to clarify whether resistance reflects poor adherence or directly increases the risk of clinical events via exhaustion of drug options.