Context:Combination antiretroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV)-infected adults and children. Objectives:To estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART -between January 1,2001,and December 31,2004 -in HIV-infected infants,children,and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era. Design,Setting,and Participants:Ongoing,multicenter,prospective cohort study designed to examine long-term outcomes in HIV-infected children. The study population included 2767 children enrolled between September 15,2000,and December 31,2004,with information entered in the database up to August 1,2005,when data analysis was conducted. The pre-HAART era comparison population included 3331 children enrolled in 13 PACTG protocols from October 1988 to August 1998.Main Outcome Measures:First occurrence of each of the 29 targeted infections. Results:Seventy-five percent of the children were enrolled in 2000 and 2001,90%acquired HIV perinatally,52%were girls,and 59%were black. The median age was 8.2 years (range,6-13 years). The median duration of follow-up was 3.4 years.Overall,553 first episodes of a specific infection occurred among 395 (14%) of the study participants. The number of events for the 4 most common first-time infections and their incidence rates (IRs) per 100 person-years were 123 bacterial pneumonia (IR,2.15; 95%confidence interval CI ,1.79-2.56),77 herpes zoster (IR,1.11; 95%CI,0.88-1.39),57 dermatophyte infections (IR,0.88; 0.67-1.14),and 52 oral candidiasis (IR,0.93; 95%CI,0.70-1.22). Incidencerates of first bacteremia,Pneumocystis jeroveci pneumonia,disseminated Mycobacterium avium complex,lymphoid interstitial pneumonitis,systemic fungal infection,cytomegalovirus retinitis,and tuberculosis were all less than 0.50 per 100 person-years. There were no statistically significant linear trends in incidence for any of the 29 infections over the 4 calendar years. However,infection rates were significantly lower than those reported in the PACTG in the pre-HAART era. The pre-HAART IRs were as follows:for bacterial pneumonia,IR,11.1; 95%CI,10.3-12.0; bacteremia,IR,3.3; 95%CI,2.9-3.8; herpes zoster,IR,2.9; 95%CI,2.6-3.3; disseminated M avium complex,IR,1.8; 95%CI,1.5-2.1; P jeroveci,IR,1.3; 95%CI,1.1-1.6; oral candidiasis,IR,1.2;95%CI,1.0-1.5; cytomegalovirus retinitis,IR,0.5; 95%CI,0.3-0.6; and tuberculosis,IR,0.2; 95%CI,0.1-0.4.Conclusions:Opportunistic infections and other related infections are uncommon in children in the HAART era,and infection rates continue to be lower than those reported in the pre-HAART era. Continued surveillance is important to assess the long-term effect of HAART on the occurrence of opportunistic and other related in fections in children. Context: Combination antiretroviral therapy or highly active antiretroviral therapy (HAART) has resulted in a dramatic decline in the incidence of opportunistic and other infections in human immunodeficiency virus (HIV) -infected adults and children. Objectives: To estimate the incidence of 29 targeted opportunistic and other infections occurring in the era of HAART -between January 1,2001, and December 31, 2004 -in HIV-infected infants, children, and adolescents followed up in Pediatric AIDS Clinical Trials Group (PACTG) 219C; to compare incidence rates in the HAART era to those of the pre-HAART era; and to test for linear trends over time in the HAART era. Design, Setting, and Participants: Ongoing, multicenter, prospective cohort study designed to examine long-term outcomes in HIV-infected The study population included 2767 children enrolled between September 15, 2000, and December 31, 2004, with information entered in the database up to August 1,2005, when data analysis was conducted. pre-HAART era comparison included 3331 children enrolled in 13 PACTG protocols from October 1988 to August 1998. Main Outcome Measures: First occurrence of each of the 29 targeted infections. Results: Seventy-five percent of the children were enrolled in 2000 and 2001 The median age was 8.2 years (range, 6-13 years). The median duration of follow-up was 3.4 years. Overall, 553 first episodes of The number of events for the 4 most common first-time infections and their incidence rates (IRs) per 100 person-years were 123 bacterial pneumonia (IR, 2.15; 95 % confidence interval CI, 1.79-2.56), 77 herpes zoster (IR, 1.11; 95% CI 0.88-1.39), 57 dermatophyte infections (IR, 0.88; 0.67-1.14), and 52 oral candidiasis % CI, 0.70-1.22). Incidences of first bacteremia, Pneumocystis jeroveci pneumonia, disseminated Mycobacterium avium complex, lymphoid intersThere are no significant significant linear trends in incidence for any of the 29 infections over the 4 calendar years. However, infection rates were significantly lower than 0.50 per 100 person-years. lower than those reported in the PACTG in the pre-HAART era. The pre-HAART IRs were as follows: for bacterial pneumonia, IR, 11.1; 95% CI, 10.3-12.0; -3.8; herpes zoster, IR, 2.9; 95% CI, 2.6-3.3; disseminated M avium complex, IR, 1.8; 95% CI, 1.5-2.1; Pjeroveci, IR, 95% CI, 1.0-1.5; cytomegalovirus retinitis, IR; 0.5; 95% CI, 0.3-0.6; and tuberculosis, IR, 0.2; 95% CI, 0.1-0.4. Configs: Opportunistic infections and other related infections are uncommon in children in the HAART era, and infection rates continue to be lower than those reported in the pre-HAART era. Continued surveillance is important to assess the long-term effect of HAART on t he occurred of opportunistic and other related in fections in children.