Ellen C Caniglia1, Andrew Phillips2, Kholoud Porter2, Caroline A Sabin2, Alan Winston3, Roger Logan1, John Gill4, Marie-Anne Vandenhende5, Diana Barger6, Sara Lodi1, Santiago Moreno7, José Ramón Arribas8, Antonio Pacheco9, Sandra W Cardoso10, George Chrysos11, Charalabos Gogos12, Sophie Abgrall13,14, Dominique Costagliola13, Laurence Meyer15,16, Remonie Seng15,16, Ard van Sighem17, Peter Reiss17,18,19, Roberto Muga20, Santiago Pérez Hoyos21, Dominique Braun22, Christoph Hauser23, Pilar Barrufet24, Maria Leyes25, Janet Tate26, Amy Justice27, Miguel A Hernán1,28,29. 1. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 2. University College London, London, United Kingdom. 3. Imperial College, London, United Kingdom. 4. Southern Alberta HIV Clinic, University of Calgary, Calgary, Alberta, Canada. 5. MCU-PH Service Médecine Interne et Maladies Infectieuses-Pr Bonnet Hôpital Saint-André CHU Bordeaux, Bordeaux, France. 6. Université de Bordeaux, Bordeaux, France. 7. Ramón y Cajal Hospital, IRYCIS, University of Alcalá de Henares, Madrid, Spain Madrid, Spain. 8. Hospital La Paz, Spain. 9. Programa de Computação Científica, FIOCRUZ, Rio de Janeiro, Madrid, Brazil. 10. INI-Fiocruz, Rio de Janeiro, Brazil. 11. Infectious Diseases Unit, "Tzaneion" General Hospital of Piraeus, Athens, Greece. 12. University of Patras, Athens, Greece. 13. INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Sorbonne Universités, UPMC Univ Paris 06, Paris, France. 14. Service de Médecine Interne, Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Antoine Béclère, Clamart, France. 15. Université Paris Sud, INSERM CESP U1018, Paris, France. 16. Service de Santé Publique, AP-HP, Hopital de Bicêtre, le Kremlin Bicêtre, France. 17. Stichting HIV Monitoring, Amsterdam, the Netherlands. 18. Division of Infectious Diseases, Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 19. Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands. 20. Servei de Medicina Interna, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain. 21. Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. 22. Universitätsspital Zürich, Zürich, Switzerland. 23. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. 24. Hospital de Mataró Mataró, Barcelona, Spain. 25. HUSE (Son Espases Universitary Hospital), Palma de Mallorca, Spain. 26. Yale University School of Medicine, New Haven, CT. 27. Yale University, New Haven, CT. 28. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA. 29. Harvard-MIT Division of Health Sciences and Technology, Boston, MA.
Abstract
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest. We evaluated 4 neuroAIDS conditions: HIV dementia and the opportunistic infections toxoplasmosis, cryptococcal meningitis, and progressive multifocal leukoencephalopathy. For each outcome, we estimated hazard ratios for atazanavir, lopinavir, and darunavir compared with efavirenz via a pooled logistic model. Our models were adjusted for baseline demographic and clinical characteristics. RESULTS: Twenty six thousand one hundred seventy-two individuals initiated efavirenz, 5858 initiated atazanavir, 8479 initiated lopinavir, and 4799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% confidence intervals) were 1.72 (1.00 to 2.96) for atazanavir, 2.21 (1.38 to 3.54) for lopinavir, and 1.41 (0.61 to 3.24) for darunavir. The respective hazard ratios (95% confidence intervals) for the combined end point were 1.18 (0.74 to 1.88) for atazanavir, 1.61 (1.14 to 2.27) for lopinavir, and 1.36 (0.74 to 2.48) for darunavir. The results varied in subsets defined by calendar year, nucleoside reverse transcriptase inhibitor backbone, and age. CONCLUSION: Our results are consistent with an increased risk of neuroAIDS after initiating lopinavir compared with efavirenz, but temporal changes in prescribing trends and confounding by indication could explain our findings.
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