Hugues Melliez1,2, Murielle Mary-Krause1, Laurence Bocket3, Marguerite Guiguet1, Sophie Abgrall1,4, Pierre De Truchis5, Christine Katlama1,6, Guillaume Martin-Blondel7,8, Aurelia Henn9, Matthieu Revest10, Olivier Robineau2, Marie-Aude Khuong-Josses11, Anna Canestri12, Nathalie De Castro13, Véronique Joly14, Saadia Mokhtari15, Karine Risso16, Jacques Gasnault17, Dominique Costagliola1. 1. Sorbonne Universités, UPMC Université Paris, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique. 2. Service Universitaire des Maladies Infectieuses et du Voyageur, Hopital Gustave Dron, Tourcoing. 3. Centre de Pathologies-Biologie, Centre Hospitalier Regional et Universitaire, Lille. 4. Service de Médecine Interne et Immunologie Clinique, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris (AP-HP), Clamart. 5. Unité d'Infectiologie, Hôpital Raymond Poincaré, AP-HP, Garches. 6. Département des Maladies Infectieuses et Tropicales, Hôpital Pitié Salpêtrière, AP-HP, Paris. 7. Service des Maladies Infectieuses et Tropicales, CHU de Toulouse. 8. Centre de Physiopathologie de Toulouse Purpan, INSERM UMR. 9. Service d'Immunologie Clinique et Maladies Infectieuses, Hôpital Henri Mondor, AP-HP, Créteil. 10. Service de Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Rennes. 11. Service de Maladies Infectieuses et Tropicales, Hôpital Delafontaine, Saint-Denis. 12. Service des Maladies infectieuses et tropicales, Hôpital Tenon. 13. Hôpital Saint-Louis. 14. Hôpital Bichat, Service des Maladies Infectieuses et Tropicales, AP-HP, Paris. 15. Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Marseille. 16. Service d'Infectiologie, Hôpital de l'Archet, Nice. 17. Service de Médecine Interne, Hôpital Bicêtre, AP-HP, Le Kremlin-Bicêtre, France.
Abstract
Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). Methods: We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. Results: PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95). Conclusions: Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.
Background: Risk factors for progressive multifocal leukoencephalopathy (PML) in individuals with human immunodeficiency virus (HIV) infection are poorly documented in the era of combination antiretroviral therapy (cART). Methods: We studied HIV-1-infected individuals aged ≥15 years who had no history of PML and were prospectively followed up between 1997 and 2011 in the French Hospital Database on HIV (FHDH-ANRS CO4) cohort. Cox models were used to calculate adjusted hazard ratios (HRs), focusing on sub-Saharan origin, suggested to be protective, and recent cART initiation, potentially associated with an increased risk of PML. Results: PML developed in 555 individuals, in 57 during the first 6 months of cART. From 1997-2000 to 2009-2011, the incidence fell from 1.15 (95% confidence interval [CI], .98-1.31) to 0.49 (.37-.61) per 1000 person-years. Sub-Saharan African origin had no clear influence (HR, 0.80; 95% CI, .58-1.11). Compared with men who have sex with men, injection drug users (IDUs) were at higher risk (HR, 1.80 [95% CI, 1.32-2.45] for male and 1.68 [1.13-2.48] for female IDUs). When IDUs were excluded, hepatitis C virus seropositivity was associated with an increased risk (HR, 1.40; 95% CI, 1.02-1.93). Compared with no cART initiation, initiation <6 months previously was associated with PML onset (HR, 4.91; 95% CI, 2.42-9.95). Conclusions: Recent cART initiation is associated with an increased risk of PML, as are injection drug use and hepatitis C virus seropositivity. Sub-Saharan African origin had no protective effect.