Time to Virological Failure of 3 Classes of Antiretrovirals after Initiation of Highly Active Antiretroviral Therapy: Results from the EuroSIDA Study Group

Objective. The purpose of the present study was to determine the prevalence and incidence of virological triple drug–class failure (TCF) and to summarize the clinical outcome for patients who started receiving highly active antiretroviral therapy (HAART). Methods. The present study is an observational longitudinal study of 3496 treatment-experienced (TE) and treatment-naive (TN) patients monitored from the time they started receiving HAART (baseline) until TCF occurred (as determined on the basis of viral loads), until AIDS was newly diagnosed, or until death. Results. Four hundred forty-five patients (12.7%) had TCF; 370 (16.6%) of 2230 patients were TE, and 75 (5.9%) of 1266 patients were TN. At 6 years after starting HAART, 21.4% of TE and 11.2% of TN patients had TCF ( ). The prevalence of TCF at or after 2002 was 15.5% in TE patients and 4.8% in TN patients. TN P ! .0001 patients had a 32% annual increase in the incidence of TCF (95% confidence interval [CI], 14%–54%; P ! ); at 5 years after starting HAART, the rate was comparable for TE and TN patients (3.3 and 3.4 cases/100 .0001 person-years of follow-up [PYFU], respectively). The incidence of new cases of AIDS or death was 2.7 cases/100 PYFU in patients who did not experience TCF and 5.0 cases/100 PYFU in patients who did experience TCF, an estimated 36% increase with each category of TCF (95% CI, 19%–56%; ). P ! .0001 Conclusion. The prevalence of TCF was low after patients started receiving HAART, particularly among TN patients. Despite the influx of patients who had started receiving HAART more recently, the prevalence of TCF increased over calendar time. Patients with TCF had a higher incidence of newly diagnosed AIDS or death. Treatment of patients with TCF deserves further investigation. One of the goals of highly active antiretroviral therapy (HAART) is to reduce the viral load to below the limit of detection, which reduces the chances of further viral evolution in response to therapeutic selection pressures. Despite an initial good response to HAART, the viral load may rebound in some patients. This phenomenon