Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

Abstract

Objective: To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design: Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. Methods: 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. Results: The risk of Kaposi sarcoma was very high during months 1–3 on cART (N = 160, RR_Crude 3.94, 95% CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RR_Adj 1.25, 95% CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N = 84, RR_Crude 1.80, 95% CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RR_Adj 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). Conclusion: 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.