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. 2022 Aug 25;75(2):297-304.
doi: 10.1093/cid/ciab883.

Discrimination and Calibration of the Veterans Aging Cohort Study Index 2.0 for Predicting Mortality Among People With Human Immunodeficiency Virus in North America

Kathleen A McGinnis  1 , Amy C Justice  1   2 , Richard D Moore  3 , Michael J Silverberg  4 , Keri N Althoff  3 , Maile Karris  5 , Viviane D Lima  6 , Heidi M Crane  7 , Michael A Horberg  8 , Marina B Klein  9 , Stephen J Gange  3 , Kelly A Gebo  3 , Angel Mayor  10 , Janet P Tate  1   11 ; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)a of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) and Veterans Aging Cohort Study (VACS)
Collaborators, Affiliations

Discrimination and Calibration of the Veterans Aging Cohort Study Index 2.0 for Predicting Mortality Among People With Human Immunodeficiency Virus in North America

Kathleen A McGinnis et al. Clin Infect Dis. .

Abstract

Background: The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality.

Methods: Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age <50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or >500 copies/mL, CD4 count <350 or ≥350 cells/µL, and years 1999-2009 or 2010-2018. Because mortality rates have decreased over time, the final model was limited to 2010-2018.

Results: Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830-.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809-.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups.

Conclusions: Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Keywords: HIV; VACS Index 2.0; calibration; mortality.

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Conflict of interest statement

Potential conflicts of interest. K. N. A. reports receiving fees as a consultant from the All of Us Research Program (NIH) and received fees as a scientific advisory board member from Trio Health. M. K. reports grants or contracts from Gilead Sciences and ViiV Healthcare outside the submitted work; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from ViiV Healthcare for Medscape, APLA Health for DKBMed, and SAGE; and a leadership or fiduciary role for Being Alive San Diego. H. M. C. reports grants or contracts from AHRQ and ViiV paid to her institution outside the submitted work, and participation on the NIH Office of AIDS Research Advisory Board. M. J. S. reports a past grant paid to his institution from Gilead Sciences outside the submitted work. V. D. L. has received a grant from the CIHR, unrelated to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Discrimination of 5-year all-cause mortality for Veterans Aging Cohort Study (VACS) Index 1.0 (circles on the left) and VACS Index 2.0 (triangles on the right), in combined VACS and North American AIDS Cohort Collaboration data, by subgroup (n=45291), 1999–2018. Abbreviations: HIV, human immunodeficiency virus; NA-ACCORD, North American AIDS Cohort Collaboration.
Figure 2.
Figure 2.
Five-year all-cause mortality rates by Veterans Aging Cohort Study (VACS) Index 2.0 for important subgroups, 1999–2018. Observed 5-year mortality is shown with 95% confidence intervals. Solid lines reflect predicted mortality calculated using combined VACS and North American AIDS Cohort Collaboration subset (n=45291). Abbreviations: HIV, human immunodeficiency virus; NA-ACCORD, North American AIDS Cohort Collaboration.
Figure 3.
Figure 3.
Distribution of combined Veterans Aging Cohort Study (VACS) and North American AIDS Cohort Collaboration subset for 2010–2018 by VACS Index 2.0 (n=23614).
Figure 4.
Figure 4.
Predicted 1-, 2-, and 5-year all-cause mortality by Veterans Aging Cohort Study (VACS) Index 2.0 for 2010–2018, calculated using combined VACS and North American AIDS Cohort Collaboration (NA-ACCORD) subset (n=23614).
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