TY - JOUR
T1 - Viremia copy-years and mortality among combination antiretroviral therapy-initiating HIV-positive individuals
T2 - How much viral load history is enough?
AU - Wang, Ruibin
AU - Haberlen, Sabina A.
AU - Palella, Frank J.
AU - Mugavero, Michael J.
AU - Margolick, Joseph B.
AU - Macatangay, Bernard J.C.
AU - Martinez-Maza, Otoniel
AU - Jacobson, Lisa P.
AU - Abraham, Alison G.
N1 - Funding Information:
Data in this article were collected by the Multicenter AIDS Cohort Study (MACS) with centers at Baltimore (U01-AI35042): The Johns Hopkins University Bloom-berg School of Public Health: J.B.M. (PI), Todd Brown (PI), Jay Bream, Adrian Dobs, Michelle Estrella, W. David Hardy, Lisette Johnson-Hill, Sean Leng, Anne Monroe, Cynthia Munro, Michael W. Plankey, Wendy Post, Ned Sacktor, Jennifer Schrack, Chloe Thio; Chicago (U01-AI35039): Feinberg School of Medicine, Northwestern University and Cook County Bureau of Health Services: Steven M. Wolinsky (PI), Sheila Badri, Dana Gabuzda, F.J.P., Sudhir Penugonda, John P. Phair, Susheel Reddy, Matthew Stephens, Linda Teplin; Los Angeles (U01-AI35040): University of California, UCLA Schools of Public Health and Medicine: Roger Detels (PI), O.M.-M. (PI), Otto Yang (Co-PI), Peter Anton, Robert Bolan, Elizabeth Breen, Anthony Butch, Shehnaz Hussain, Beth Jamieson, John Oishi, Harry Vinters, Dorothy Wiley, Mallory Witt, Stephen Young, Zuo Feng Zhang; Pittsburgh (U01-AI35041): University of Pittsburgh, Graduate School of Public Health: Charles R. Rinaldo (PI), Lawrence A. Kingsley (PI), Jeremy J. Martinson (PI), James T. Becker, Phalguni Gupta, Kenneth Ho, Susan Koletar, John W. Mellors, Anthony J. Silvestre, Ronald D. Stall; Data Coordinating Center (UM1-AI35043): The Johns Hopkins University Bloomberg School of Public Health: L.P.J. (PI), Gypsyamber D’Souza (PI), A.G.A, Keri Althoff, Michael Collaco, Priya Duggal, S.A.H., Eithne Keelaghan, Heather McKay, Alvaro Muñoz, Derek Ng, Anne Rostich, Eric C. Seaberg, Sol Su, Pamela Surkan, Nicholas Wada. Institute of Allergy and Infectious Diseases: Robin E. Huebner; National Cancer Institute: Geraldina Dominguez. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR or NCATS. The MACS website is located at http://aidscohortstudy.org/.
Funding Information:
This work was supported by grants U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, UM1-AI35043 from the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects in the MACS was provided by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH).
Publisher Copyright:
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Objective: Ongoing HIV replication while receiving combination antiretroviral therapy (cART) may reduce survival. Viremia copy-years (VCY) has shown improved mortality risk prediction over single time-point viral load measures. However, the timing of a patient s viral load history most associated with later mortality has not been studied. Here we determined the optimal duration and temporality of viral load history for predicting mortality. Design: Survival analysis among HIV-positive men who initiated cART in the Multicenter AIDS Cohort Study (1995 2015). Methods: VCY measures were derived from area-under-The-viral load-curve. The overall VCY based upon the complete post-cART viral load history was compared with 20 VCYs derived from viral loads assessed during different shorter time periods (the most recent 1 10 years and initial 1 10 years following cART initiation) for associations with mortality. Results: Each 10-fold increase in VCYs based on the most recent 3 8 years was significantly associated with 23 26% decrease in survival times, a magnitude of effect greater than that of the most recent viral load (16%). These associations were independent of CD4 cell count and single time-point viral loads. In addition, the degree of precART immunodeficiency did not affect the mortality prognostic value of VCY based on viral loads in the most recent 3 years. Conversely, the overall VCY and VCYs based on viral loads immediately following cART initiation were not independent predictors of mortality. Conclusion: Among cART-Treated men, VCY based upon viral loads in the recent 3 years (six viral loads) has a mortality prognostic value greater than that of the overall VCY and single time-point viral loads, making the former a more feasible measure for use.
AB - Objective: Ongoing HIV replication while receiving combination antiretroviral therapy (cART) may reduce survival. Viremia copy-years (VCY) has shown improved mortality risk prediction over single time-point viral load measures. However, the timing of a patient s viral load history most associated with later mortality has not been studied. Here we determined the optimal duration and temporality of viral load history for predicting mortality. Design: Survival analysis among HIV-positive men who initiated cART in the Multicenter AIDS Cohort Study (1995 2015). Methods: VCY measures were derived from area-under-The-viral load-curve. The overall VCY based upon the complete post-cART viral load history was compared with 20 VCYs derived from viral loads assessed during different shorter time periods (the most recent 1 10 years and initial 1 10 years following cART initiation) for associations with mortality. Results: Each 10-fold increase in VCYs based on the most recent 3 8 years was significantly associated with 23 26% decrease in survival times, a magnitude of effect greater than that of the most recent viral load (16%). These associations were independent of CD4 cell count and single time-point viral loads. In addition, the degree of precART immunodeficiency did not affect the mortality prognostic value of VCY based on viral loads in the most recent 3 years. Conversely, the overall VCY and VCYs based on viral loads immediately following cART initiation were not independent predictors of mortality. Conclusion: Among cART-Treated men, VCY based upon viral loads in the recent 3 years (six viral loads) has a mortality prognostic value greater than that of the overall VCY and single time-point viral loads, making the former a more feasible measure for use.
KW - HIV
KW - MSM
KW - all-cause mortality
KW - combination antiretroviral therapy
KW - viremia copy-years
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U2 - 10.1097/QAD.0000000000001986
DO - 10.1097/QAD.0000000000001986
M3 - Article
C2 - 30379686
AN - SCOPUS:85055796412
VL - 32
SP - 2547
EP - 2556
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 17
ER -