Sunday, December 2, 2012

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

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

Nov 2012


aInserm UMR-S 943; UPMC Univ Paris 06 UMR-S 943; INSERM-TRANSFERT; Paris, France bAP-HP, Hôpital Antoine Béclère, Service de médecine interne et d'immunologie clinique; Université Paris-Sud, Clamart, France cINSERM UMR-S 943; AP-HP, Groupe Hospitalier Cochin Hôtel-Dieu, Unité de biostatistique et épidémiologie; Université Paris Descartes, Paris, France dCentre Hospitalier de Tourcoing, Service universitaire des maladies infectieuses et du voyage, Tourcoing, France eAP-HP, Hôpital Saint Louis, Service des maladies infectieuses et tropicales, Paris, France fAP-HP, Hôpital Henri-Mondor, Service d'immunologie clinique, Créteil, France gAP-HP, Hôpital Saint Antoine, Service des maladies infectieuses et tropicales, Paris, France hHôpitaux Universitaires de Strasbourg, Le Trait d'Union - Centre de soins de l'infection par le VIH, Strasbourg, France iUniversité Paris Descartes; AP-HP, Hôpital Cochin, Paris, France jUniversité Denis Diderot Paris 7; AP-HP Hôpital Bichat-Claude Bernard, Service de Maladies infectieuses et Tropicales, Paris, France kHôpital l'Archet, Département de médecine interne; Université de Nice-Sophia Antipolis, Nice, France lHôpital Ambroise Paré, Service de médecine interne, Boulogne, France mCHU Pontchaillou, Service des Maladies Infectieuses et de Réanimation Médicale, Rennes, France nAP-HP, Hôpital Raymond Poincaré, Service de médecine aigue spécialisée, Garches, France oINSERM UMR-S 943; UPMC Univ Paris 06 UMR-S 943, Paris, France pDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD USA.


OBJECTIVE: Determine if incident AIDS-defining Kaposi sarcoma (KS) or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. 

DESIGN: Compare risk for KS and PJP by time on cART and CD4 reconstitution. 

METHODS: 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. 

RESULTS: 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/mm) or PJP (61/mm) within 3 months compared with those without (>250/mm). Notably, median CD4 change was +44 cells/month with incident KS within 3 months of cART initiation versus 0 cells/month with incident PJP . 

CONCLUSIONS: 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.

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