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

Lacombe, Jean-Marc; Boue, François; Grabar, Sophie; Viget, Nathalie; Gazaignes, Sandrine; Lascaux-Cametz, Anne-Sophie; Pacanowski, Jérome; Partisani, Marialuisa; Launay, Odile; Matheron, Sophie; Rosenthal, Eric; Rouveix, Elisabeth; Tattevin, Pierre; de Truchis, Pierre; Costagliola, Dominique; Goedert, James J.

doi: 10.1097/QAD.0b013e32835cba6c
Epidemiology and Social

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, 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).

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.

aInserm UMR-S 943, UPMC Univ Paris 06 UMR-S 943, INSERM-TRANSFERT, Paris

bAP-HP, Hôpital Antoine Béclère, Service de médecine interne et d’immunologie clinique, Université Paris-Sud, Clamart

cINSERM UMR-S 943, AP-HP, Groupe Hospitalier Cochin Hôtel-Dieu, Unité de biostatistique et épidémiologie, Université Paris Descartes, Paris

dCentre Hospitalier de Tourcoing, Service universitaire des maladies infectieuses et du voyage, Tourcoing

eAP-HP, Hôpital Saint Louis, Service des maladies infectieuses et tropicales, Paris

fAP-HP, Hôpital Henri-Mondor, Service d’immunologie clinique, Créteil

gAP-HP, Hôpital Saint Antoine, Service des maladies infectieuses et tropicales, Paris

hHôpitaux Universitaires de Strasbourg, Le Trait d’Union–Centre de soins de l’infection par le VIH, Strasbourg

iUniversité Paris Descartes, AP-HP, Hôpital Cochin

jUniversité Denis Diderot Paris 7, AP-HP Hôpital Bichat-Claude Bernard, Service de Maladies infectieuses et Tropicales, Paris

kHôpital l’Archet, Département de médecine interne, Université de Nice-Sophia Antipolis, Nice

lHôpital Ambroise Paré, Service de médecine interne, Boulogne

mCHU Pontchaillou, Service des Maladies Infectieuses et de Réanimation Médicale, Rennes

nAP-HP, Hôpital Raymond Poincaré, Service de médecine aigue spécialisée, Garches

oINSERM UMR-S 943, UPMC Univ Paris 06 UMR-S 943, Paris, France

pDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.

Correspondence to Dr James J. Goedert, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7068, Rockville, MD 20852, USA. E-mail: goedertj@mail.nih.gov

Received 26 September, 2012

Revised 5 November, 2012

Accepted 16 November, 2012

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