Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Sara Lodi, Julia Del Amo, Santiago Moreno, Heiner C. Bucher, Hansjakob Furrer, Roger Logan, Jonathan Sterne, Santiago Pérez-Hoyos, Inma Jarrín, Andrew Phillips, Ashley Olson, Ard Van Sighem, Peter Reiss, Caroline Sabin, Sophie Jose, Amy Justice, Joseph Goulet, José M. Miró, Elena Ferrer, Laurence MeyerRémonie Seng, Georgia Vourli, Anastasia Antoniadou, Francois Dabis, Mari-Anne Vandenhede, Dominique Costagliola, Sophie Abgrall, Miguel A. Hernán, Miguel Hernan, L. Bansi, T. Hill, C. Sabin, J. Anderson, M. Johnson, T.W. Kuijpers, J.T.M. Van Der Meer, J. Veenstra, K.D. Lettinga, M.J.H. Pronk, H.G. Sprenger, R. Doedens, E.H. Scholvinck, S. Van Assen, W.F.W. Bierman, L.J. Bont, M. Van Den Berge, F. Montolio, J. Lim, A.M. Saeed, F. Wallis, The HIV-CAUSAL Collaboration

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Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+cell count and HIV-RNA via inverse probability weighting.Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.
Original languageEnglish
Pages (from-to)2461-2473
Number of pages13
Issue number16
Publication statusPublished - 23-Oct-2014


  • HIV
  • Immune reconstitution inflammatory syndrome
  • Incidence
  • Inverse probability weighting
  • Unmasking
  • antiretrovirus agent
  • acquired immune deficiency syndrome
  • adult
  • article
  • candidiasis
  • CD4 lymphocyte count
  • cryptococcosis
  • Cytomegalovirus retinitis
  • female
  • follow up
  • Herpes simplex virus
  • highly active antiretroviral therapy
  • human
  • immune reconstitution inflammatory syndrome
  • incidence
  • Kaposi sarcoma
  • major clinical study
  • male
  • nonhodgkin lymphoma
  • opportunistic infection
  • outcome assessment
  • progressive multifocal leukoencephalopathy
  • tuberculosis
  • virus infection

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