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Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-up

Hogg, Robert S.a,b; Heath, Katherinea,b; Bangsberg, Davidc; Yip, Benitaa; Press, Natashaa; O'Shaughnessy, Michael V.a,d; Montaner, Julio S. G.a,e

Epidemiology & Social

Objective: To characterize the impact of intermittent use of triple drug antiretroviral therapy on survival.

Design, setting and participants: 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.

Main outcome measure: Cumulative all-cause mortality rates from the start of triple drug antiretroviral therapy to 30 September 2000.

Results: 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.

Conclusion: Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.

From the aBC Centre for Excellence in HIV/AIDS, the bDepartment of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, the cEpidemiology and Prevention Interventions Center, Division of Infectious Diseases and the Positive Health Program, San Francisco General Hospital, California, USA, the dDepartment of Pathology and Laboratory Medicine, and the eDepartment of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Requests for reprints to: R. Hogg, Division of Epidemiology and Population Health, BC Centre for Excellence in HIV/AIDS, 608-1081 Burrard Street, Vancouver, B.C. V6Z 1Y6, Canada.

Received: 12 July 2001;

revised: 20 December 2001; accepted: 7 January 2002.

© 2002 Lippincott Williams & Wilkins, Inc.