Cumulative Viral Load Predicts All-Cause and AIDS-Related Mortality After Initiation of ART

Michael J Mugavero, Andrew O Westfall, M John Gill, M Saag, Sophie Abgrall, Gerd Fätkenheuer, Peter Reiss, Suzanne Ingle, Margaret May, Jonathan Sterne

Research output: Contribution to conferenceConference Posterpeer-review

Abstract

Background: The prognostic value of cross-sectional viral load (VL) measures for clinical events following ART initiation is well established but the best way to quantify their association with clinical events and death over time is unclear. Methodology: Treatment-naive patients starting ART between January 2000 and December 2009 in one of 17 cohorts participating in the ART Cohort Collaboration (ART-CC) were included. Time-updated viremia copy-years (VCY) following ART initiation (“baseline”). VCY estimates the cumulative plasma viral burden based on the area under the VL curve and was calculated daily for each patient. We assumed a lower limit of detection of 500 copies/ml: values <500 were set to 250 for calculation of VCY). Procedures for standardized coding of deaths were adapted from the CoDe protocol. We used Cox models to estimate associations (hazard ratio [HR], 95% CI) of baseline and time-updated viral load, and time-updated VCY, with all-cause, AIDS-related, and non-AIDS-related mortality. All models were adjusted for baseline age, sex, transmission risk group and cohort, and time-updated CD4 count. Results: Among 33563 patients (mean age 39 years, male 71%, mean baseline CD4 217 cells/μL), a mean 13 viral load measures were available during mean 3.2 years following ART initiation. 1341 patients died, including 503 AIDS-related deaths, 614 non-AIDS-related deaths, and 224 unclassifiable/ unknown deaths. All viral load measures predicted all-cause mortality, but time-updated VCY remained strongly predictive when adjusted for the other viral load measures. Similar patterns, with stronger associations, were observed for AIDS-related mortality. Associations with non-AIDS mortality were modest, with little evidence that any of the three VL measures independently predicts non-AIDS mortality. Conclusions: Cumulative plasma viral burden following ART initiation better predicts all-cause and AIDS-related mortality than most recent VL, independent of time-updated CD4 count. None of the VL measures considered was clearly associated with non-AIDS mortality.
Original languageEnglish
Publication statusPublished - 3 Mar 2014
EventConference on Retroviruses and Opportunistic Infections - Boston, United States
Duration: 3 Mar 20146 Mar 2014

Conference

ConferenceConference on Retroviruses and Opportunistic Infections
CountryUnited States
CityBoston
Period3/03/146/03/14

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