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To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation.Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution.In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests.The risk of Kaposi sarcoma was very high during months 1–3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/μl) or PJP (61 cells/μl) within 3 months than in those who did not develop these conditions (>250 cells/μl). Notably, median CD4 cell count change was +44 cells/μl per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/μl per month with incident PJP (P = 0.0003).Failure of CD4 cell count reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.