Commonly Prescribed Antiretroviral Therapy Regimens and Incidence of AIDS-Defining Neurological Conditions

Ellen C Caniglia, Andrew Phillips, Kholoud Porter, Caroline A Sabin, Alan Winston, Roger Logan, John Gill, Marie-Anne Vandenhende, Diana Barger, Sara Lodi, Santiago Moreno, José Ramón Arribas, Antonio Pacheco, Sandra W Cardoso, George Chrysos, Charalabos Gogos, Sophie Abgrall, Dominique Costagliola, Laurence Meyer, Remonie Seng, Ard van Sighem, Peter Reiss, Roberto Muga, Santiago Pérez Hoyos, Dominique Braun, Christoph Hauser, Pilar Barrufet, Maria Leyes, Janet Tate, Amy Justice, Miguel A Hernán

The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) 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 four 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. 26,172 individuals initiated efavirenz, 5,858 initiated atazanavir, 8,479 initiated lopinavir, and 4,799 initiated darunavir. Compared with efavirenz, the adjusted HIV dementia hazard ratios (95% CIs) were 1.72 (1.00, 2.96) for atazanavir, 2.21 (1.38, 3.54) for lopinavir, and 1.41 (0.61, 3.24) for darunavir. The respective hazard ratios (95% CIs) for the combined endpoint were 1.18 (0.74, 1.88) for atazanavir, 1.61 (1.14, 2.27) for lopinavir, and 1.36 (0.74, 2.48) for darunavir. The results varied in subsets defined by calendar year, NRTI backbone, and age. 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.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.