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

Nov 2012

Lacombe JM, Boue F, Grabar S, Viget N, Gazaignes S, Lascaux-Cametz AS, Pacanowski J, Partisani M, Launay O,Matheron S, Rosenthal E, Rouveix E, Tattevin P, de Truchis P, Costagliola D, Goedert JJ.

Source

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.

Abstract

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.

Lippincott Williams Wilkins