BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We analysed data from 22,217 treatment-naive HIV-1-infected adults who had started HAART and were followed up in one of 12 cohort studies. The probability of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to 32%. The median CD4 cell count when starting HAART increased from 170 cells per muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200 cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by 6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). INTERPRETATION: Virological response after starting HAART improved over calendar years, but such improvement has not translated into a decrease in mortality.