Changes over time in risk of initial virological failure of combination antiretroviral therapy - A multicohort analysis, 1996 to 2002

Background: Triple-combination antiretroviral therapy ( CART) for human immunodeficiency virus infection has been in use for almost a decade, but the extent to which treatment success has changed is uncertain. We examined risk of initial virological failure of CART according to the year of starting therapy. Methods: We included subjects from 5 complete clinic cohorts in Europe and Canada who started CART without previous antiretroviral therapy from 1996 to 2002 with 1 or more pre-CART viral load(VL) measurement and CD4 count. Based on the first VL measurement from 6 to 12 months after CART initiation, virological failure was defined as a VL of more than 500 copies/mL. We used the following 3 inclusion strategies: ( 1) including all subjects, with missing VL measurement counted as virological failure (n= 3825; strategy A); ( 2) including all subjects with VL measurement ( n= 3120; strategy B); and ( 3) including all subjects receiving antiretroviral therapy at VL measurement ( n= 2890; strategy C). Results: From 1996 to 2002, risk of virological failure fell from 38.9% to 24.8% for strategy A, 28.4% to 12.0% for strategy B, and 22.8% to 8.2% for strategy C. Estimated relative reductions in risk (95% confidence interval) over the 7-year period, adjusted for cohort, demographic factors, pre-CART VL and CD4 count, and previous AIDS, were 48% (39%-56%), 64%(53%-73%), and 79%(69%-85%) for strategies A, B, and C, respectively. Reductions in risk were greatest from 1996 to 1999, with weaker trends subsequently. Trends remained but were attenuated after further adjustment for the starting regimen. Conclusions: Over a 7-year period of CART use in clinical practice, risk of initial virological failure of treatment has halved at least. These data suggest the trend is due to improvements in CART regimens and greater effectiveness of their use.