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.
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.
Authors: Alison G Abraham; Bryan Lau; Steven Deeks; Richard D Moore; Jinbing Zhang; Joseph Eron; Richard Harrigan; M John Gill; Mari Kitahata; Marina Klein; Sonia Napravnik; Anita Rachlis; Benigno Rodriguez; Sean Rourke; Constance Benson; Ron Bosch; Ann Collier; Kelly Gebo; James Goedert; Robert Hogg; Michael Horberg; Lisa Jacobson; Amy Justice; Greg Kirk; Jeff Martin; Rosemary McKaig; Michael Silverberg; Timothy Sterling; Jennifer Thorne; James Willig; Stephen J Gange Journal: Am J Epidemiol Date: 2011-08-03 Impact factor: 4.897
Authors: Ayesha De Costa; Anita Shet; Nagalingeswaran Kumarasamy; Per Ashorn; Bo Eriksson; Lennart Bogg; Vinod K Diwan Journal: BMC Med Res Methodol Date: 2010-03-26 Impact factor: 4.615
Authors: Steven G Deeks; Stephen J Gange; Mari M Kitahata; Michael S Saag; Amy C Justice; Robert S Hogg; Joseph J Eron; John T Brooks; Sean B Rourke; M John Gill; Ronald J Bosch; Constance A Benson; Ann C Collier; Jeffrey N Martin; Marina B Klein; Lisa P Jacobson; Benigno Rodriguez; Timothy R Sterling; Gregory D Kirk; Sonia Napravnik; Anita R Rachlis; Liviana M Calzavara; Michael A Horberg; Michael J Silverberg; Kelly A Gebo; Margot B Kushel; James J Goedert; Rosemary G McKaig; Richard D Moore Journal: Clin Infect Dis Date: 2009-11-15 Impact factor: 9.079
Authors: Marie Ballif; Bruno Ledergerber; Manuel Battegay; Matthias Cavassini; Enos Bernasconi; Patrick Schmid; Bernard Hirschel; Hansjakob Furrer; Martin Rickenbach; Milos Opravil; Rainer Weber Journal: PLoS One Date: 2009-12-14 Impact factor: 3.240