Determine if incident AIDS-defining Kaposi sarcoma (KS) or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation.
Compare risk for KS and PJP by time on cART and CD4 reconstitution.
In the FHDH-ANRS CO4 cohort (N=66,369), KS (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 (CI) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 counts were compared by Wilcoxon rank sum tests.
KS risk was very high during months 1–3 on cART (N=160, RRCrude 3.94, CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 count (RRAdj 1.25, CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N=84, RRCrude 1.80, 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 KS (82/mm3) or PJP (61/mm3) within 3 months compared with those without (>250/mm3). Notably, median CD4 change was +44 cells/month with incident KS within 3 months of cART initiation versus 0 cells/month with incident PJP (P=0.0003).
Failure of CD4 reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional KS cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining KS.