Discrimination and Calibration of the Veterans Aging Cohort Study Index 2.0 for Predicting Mortality Among People With Human Immunodeficiency Virus in North America
Authors: McGinnis Kathleen A , Justice Amy C , Moore Richard D , Silverberg Michael J , Althoff Keri N , Karris Maile , Lima Viviane D , Crane Heidi M , Horberg Michael A , Klein Marina B , Gange Stephen J , Gebo Kelly A , Mayor Angel , Tate Janet P ,   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), Benson Constance A , Bosch Ronald J , Kirk Gregory D , Marconi Vincent , Colasanti Jonathan , Mayer Kenneth H , Grasso Chris , Hogg Robert S , Lima Viviane D , Montaner Julio S G , Sereda Paul , Salters Kate , Buchacz Kate , Li Jun , Gebo Kelly A , Moore Richard D , Moore Richard D , Jacobson Jeffrey M , Horberg Michael A , Silverberg Michael J , Thorne Jennifer E , Brown Todd , Tien Phyllis , D’Souza Gypsyamber , Smith Graham , Loutfy Mona , Gupta Meenakshi , Klein Marina B , Rabkin Charles , Kroch Abigail , Burchell Ann , Betts Adrian , Lindsay Joanne , Nijhawan Ank , Mayor Angel M , Gill M John , Martin Jeffrey N , Li Jun , Brooks John T , Saag Michael S , Mugavero Michael J , Willig James , Bamford Laura , Karris Maile , Eron Joseph J , Napravnik Sonia , Kitahata Mari M , Crane Heidi M , Sterling Timothy R , Haas David , Rebeiro Peter , Turner Megan , McGinnis Kathleen A , Justice Amy C , Moore Richard D , Althoff Keri N , Gange Stephen J , Kitahata Mari M , Lee Jennifer S , Saag Michael S , Horberg Michael A , Klein Marina B , McKaig Rosemary G , Freeman Aimee M , Moore Richard D , Althoff Keri N , Freeman Aimee M , Kitahata Mari M , Van Rompaey Stephen E , Crane Heidi M , Morton Liz , McReynolds Justin , Lober William B , Gange Stephen J , Lee Jennifer S , Hogan Brenna , You Bin , Humes Elizabeth , Gerace Lucas , Stewart Cameron , Coburn Sally 
Published: September 2021

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 &lt;50 or ≥50 years, race/ethnicity, HIV-1 RNA ≤500 or &gt;500 copies/mL, CD4 count &lt;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.