594    

Background:  Recent studies have found increasing rates of triple-class antiretroviral drug failure. We aimed to examine the incidence, prevalence, and predictors for development of triple-class antiretroviral drug failure  in a complete nationwide cohort of HIV-infected individuals.

Methods:  The Danish HIV Cohort Study, a population-based observational cohort study, from which we enrolled 2722 patients initiating HAART. Antiretroviral drugs are provided free of charge in Denmark and distributed solely through 9 clinics, ensuring inclusion of all Danish HIV patients receiving antiretroviral therapy (ART). We calculated time from start of HAART to triple-class failure and summarized failure over time. We estimated triple-class antiretroviral drug failure incidence rates using person-years analysis. Cox´ regression analysis was used to find predictors of triple-class antiretroviral drug failure.

Results:  We observed 177 triple-class antiretroviral drug failures, yielding a crude incidence rate of 1.8 (95% CI 1.6 to 2.1) per 100 person-years. The annual incidence rate peaked in 2000 at 3.7 (95% CI 2.9 to 4.8), and then declined to 0.4 (95% CI 0.2 to 1.1) in 2003. For ART-experienced patients the incidence rate reached a maximum of 4.6 (95% CI 3.3 to 6.4) in the fourth year following HAART initiation, declining to 1.4 (95% CI 0.6 to 3.2) in the sixth year. For ART-naive patients the incidence rate remained stable between 0.9 and 1.6 with no clear trend. Then, 7 years after initiation of HAART, 12.4% (95% CI 10.4 to 14.8) of all patients, 17.2% (95% CI 14.5 to 20.5) of ART-experienced patients, but only 7.0% (95% CI 4.3 to 11.2) of ART-naive patients were estimated to have triple-class antiretroviral drug failure. The prevalence of triple-class antiretroviral drug failure among patients on HAART remained stable at < 7% after 2000, with a declining trend. In crude regression analyses, an earlier year of HAART initiation, having a high viral load or a CD4 count < 200 cells/µL at the time of HAART initiation, having had an AIDS-defining event, being ART-experienced, and being young were associated with a higher risk of triple-class antiretroviral drug failure. In the multivariate model, a high viral load at the time of HAART initiation was a predictor in ART-experienced, but not in ART-naive patients. The adjusted triple-class antiretroviral drug failure risk among ART-naive patients who initiated HAART after 1999 was one-eighth of that facing ART-naive patients with HAART initiation before 1999.

Conclusions:  The risk of triple-class antiretroviral drug failure is declining in Denmark and the prevalence remains stable. Importantly, this study provides the first evidence that high antiretroviral drug pressure at the population level does not inevitably result in increasing rates of drug failure.

Keywords: Treatment Failure; Cohort Studies; Antiretroviral Therapy, Highly Active