||BACKGROUND: The risk of Kaposi's sarcoma and non-Hodgkin's lymphoma is increased in people infected with the human immunodeficiency virus-1 (HIV). Highly active antiretroviral therapy (HAART) has been widely used by HIV-infected people in North America, Europe, and Australia since about 1997. Acquired immunodeficiency syndrome (AIDS) incidence and mortality rates have fallen markedly in association with the use of HAART, but its impact on the incidence of cancer in HIV-infected people is less clear. METHODS: Cancer incidence data from 23 prospective studies that included 47 936 HIV-seropositive individuals from North America, Europe, and Australia were collated, checked, and analyzed centrally. Adjusted incidence rates (expressed as number of cancers per 1000 person-years) for Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, cervical cancer, and 20 other cancer types or sites were calculated. Rate ratios were estimated, comparing incidence rates from 1997 through 1999 with rates from 1992 through 1996, after adjustment for study, age, sex, and HIV transmission group. All statistical tests were two-sided. RESULTS: For the period from 1992 through 1999, 2702 incident cancers were reported in 138 148 person-years of observation, and more than 90% of them were either Kaposi's sarcoma or non-Hodgkin's lymphoma. The adjusted incidence rate for Kaposi's sarcoma declined from 15.2 in 1992 through 1996 to 4.9 in 1997 through 1999 (rate ratio = 0.32; 99% confidence interval [CI] = 0.26-0.40; based on 1489 and 190 cases, respectively; P<.0001). The incidence rates for non-Hodgkin's lymphoma also declined, from 6.2 to 3.6 (rate ratio = 0.58; 99% CI = 0.45-0.74; based on 623 and 134 cases, respectively; P<.0001). Among the lymphomas, the rate ratios were 0.42 (99% CI = 0.24-0.75) for cerebral lymphoma, 0.57 (99% CI = 0.39-0.85) for immunoblastic lymphoma, and 1.18 (99% CI = 0.48-2.88) for Burkitt's lymphoma (chi(2)(2) for heterogeneity = 6.2; P: =.05). There was no statistically significant change in the incidence rates for Hodgkin's disease (rate ratio = 0.77; 99% CI = 0.32-1.85; based on 38 and 12 cases, respectively; P =.4) or for cervical cancer (rate ratio = 1.87; 99% CI = 0.77-4.56; based on 19 and 17 cases, respectively; P =.07). The adjusted incidence rate for all other cancers combined was 1.7 in each time period (rate ratio = 0.96; 99% CI = 0.62-1.47; based on 126 and 54 cases, respectively). CONCLUSIONS: Since the widespread use of HAART, there have been substantial reductions in the incidence Kaposi's sarcoma and non-Hodgkin's lymphoma in HIV-infected people but, so far, no substantial change in the incidence of other cancers.