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Viremia copy-years and mortality among combination antiretroviral therapy-initiating HIV-positive individuals

how much viral load history is enough?

Wang, Ruibina; Haberlen, Sabina A.a; Palella, Frank J. Jrb; Mugavero, Michael J.c; Margolick, Joseph B.d; Macatangay, Bernard J.C.e; Martínez-Maza, Otonielf; Jacobson, Lisa P.a; Abraham, Alison G.g

doi: 10.1097/QAD.0000000000001986
Epidemiology and Social

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 pre-cART 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.

aDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

bDivision of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois

cDivision of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

dDepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

eDepartment of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania

fDepartment of Obstetrics & Gynecology, Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California

gDepartment of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Correspondence to Ruibin Wang, MHS, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 700 E. Pratt St., Suite 1000, Baltimore, MD 21202, USA. Tel: +1 410 223 1864; fax: +1 410 955 7581; e-mail:

Received 27 March, 2018

Accepted 16 July, 2018

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