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To characterize the impact of intermittent use of triple drug antiretroviral therapy on survival.Population-based analysis of 1282 antiretroviral therapy naive HIV-positive individuals aged 18 years and older in British Columbia who started triple-combination therapy between August 1996 and December 1999. Therapy use was estimated by dividing the number of months of medications dispensed by the number of months of follow-up. Intermittent therapy was defined as the participant having obtained less than 75% of their medication in the first 12 months.Cumulative all-cause mortality rates from the start of triple drug antiretroviral therapy to 30 September 2000.As of 30 September 2000, 106 subjects had died. Cumulative mortality was 3.9% (± 0.5%) at 12 months. In a multivariate model, after controlling for other variables that were significant in the univariate analyses each 100 cell decrement in baseline CD4 cell count and the intermittent use of antiretroviral drugs were associated with increased mortality with risk ratios of 1.31 [95% confidence interval (CI), 1.16–1.49;P < 0.001] and 2.90 (95% CI, 1.93–4.36;P < 0.001), respectively. In order to control for downward drift, intermittent use of therapy was measured over the first year whereas other factors were measured at the end of year 1. After adjusting for all other factors, those participants who used antiretroviral drugs intermittently were 2.97 times (95% CI, 1.33–6.62;P = 0.008) more likely to die.Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.