Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery

Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustaine...

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Published in:	Clinical infectious diseases Vol. 58; no. 9; p. 1312
Main Authors:	Engsig, Frederik N, Zangerle, Robert, Katsarou, Olga, Dabis, Francois, Reiss, Peter, Gill, John, Porter, Kholoud, Sabin, Caroline, Riordan, Andrew, Fätkenheuer, Gerd, Gutiérrez, Félix, Raffi, Francois, Kirk, Ole, Mary-Krause, Murielle, Stephan, Christoph, de Olalla, Patricia Garcia, Guest, Jodie, Samji, Hasina, Castagna, Antonella, d'Arminio Monforte, Antonella, Skaletz-Rorowski, Adriane, Ramos, Jose, Lapadula, Giuseppe, Mussini, Cristina, Force, Lluís, Meyer, Laurence, Lampe, Fiona, Boufassa, Faroudy, Bucher, Heiner C, De Wit, Stéphane, Burkholder, Greer A, Teira, Ramon, Justice, Amy C, Sterling, Tim R, M Crane, Heidi, Gerstoft, Jan, Grarup, Jesper, May, Margaret, Chêne, Geneviève, Ingle, Suzanne M, Sterne, Jonathan, Obel, Niels
Format:	Journal Article
Language:	English
Published:	United States 01.05.2014
Subjects:	Adult Anti-HIV Agents - therapeutic use Cause of Death CD4 Lymphocyte Count Cohort Studies Female Heterosexuality HIV Infections - drug therapy HIV Infections - mortality HIV Infections - transmission Humans Logistic Models Male Middle Aged Risk Factors Substance-Related Disorders - complications Viral Load mortality CD4 cell recovery risk factors sustained viral suppression HIV
ISSN:	1537-6591, 1537-6591
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Abstract	Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.
AbstractList	Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.BACKGROUNDSome human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality.We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality.METHODSWe included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality.Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death.RESULTSOf 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death.Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.CONCLUSIONSVirally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.
Author	Porter, Kholoud Riordan, Andrew Reiss, Peter Skaletz-Rorowski, Adriane De Wit, Stéphane Chêne, Geneviève Engsig, Frederik N Castagna, Antonella Ramos, Jose Boufassa, Faroudy Force, Lluís Burkholder, Greer A May, Margaret Katsarou, Olga Bucher, Heiner C Sabin, Caroline Sterling, Tim R Samji, Hasina d'Arminio Monforte, Antonella Meyer, Laurence de Olalla, Patricia Garcia Sterne, Jonathan Fätkenheuer, Gerd Gill, John Gerstoft, Jan Teira, Ramon Dabis, Francois Stephan, Christoph Guest, Jodie Justice, Amy C Lampe, Fiona Ingle, Suzanne M M Crane, Heidi Zangerle, Robert Raffi, Francois Lapadula, Giuseppe Mary-Krause, Murielle Grarup, Jesper Obel, Niels Kirk, Ole Gutiérrez, Félix Mussini, Cristina
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24457342$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Contributor	Battegay, Manuel Justice, Amy R Sterling, Tim Porter, Kholoud Riordan, Andrew Burkholder, Greer Saag, Michael Reiss, Peter Skaletz-Rorowski, Adriane Engsig, Frederik N Ramos, Jose Touloumi, Giota Boufassa, Faroudy Del Amo, Julia Ramos, José Costagliola, Dominique Gibb, Diana Bucher, Heiner C Van Sighem, Ard Sabin, Caroline Thorne, Claire Ingle, Suzanne Williams, Matthew Krause, Murielle Mary Mocroft, Amanda Wit, Ferdinand Sterne, Jonathan Fätkenheuer, Gerd Gill, John Gerstoft, Jan Teira, Ramon Dabis, Francois Guest, Jodie Lampe, Fiona Zangerle, Robert Raffi, Francois Mary-Krause, Murielle Hogg, Robert Grarup, Jesper Obel, Niels Pérez-Hoyos, Santiago Kirk, Ole Gutiérrez, Félix Mussini, Cristina Casabona, Jordi Brockmeyer, Norbert Ghosn, Jade De Wit, Stéphane Chêne, Geneviève Gussenheimer-Bartmeyer, Barbara Castagna, Antonella Crane, Heidi M Noguera-Julian, Antoni Antinori, Andrea Force, Lluís Leport, Catherine Kitahata, Mari May, Margaret Katsarou, Olga Sterling, Tim R Hamouda, Osamah Samji, Hasina Brodt, Hans-Reinhard d'Arminio Monforte, Antonella
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CorporateAuthor	Antiretroviral Therapy Cohort Collaboration (ART-CC) and the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord
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Keywords	mortality CD4 cell recovery risk factors sustained viral suppression HIV
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PublicationTitle	Clinical infectious diseases
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Snippet	Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression...
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SubjectTerms	Adult Anti-HIV Agents - therapeutic use Cause of Death CD4 Lymphocyte Count Cohort Studies Female Heterosexuality HIV Infections - drug therapy HIV Infections - mortality HIV Infections - transmission Humans Logistic Models Male Middle Aged Risk Factors Substance-Related Disorders - complications Viral Load
Title	Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery
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