Albumin, white blood cell count, and body mass index improve discrimination of mortality in HIV-positive individuals

Objective: Despite viral suppression and immune response on antiretroviral therapy, people with HIV infection experience excess mortality compared with uninfected individuals. The Veterans Aging Cohort Study (VACS) Index incorporates clinical biomarkers of general health with age, CD4+ cell count, and HIV-1 RNA to discriminate mortality risk in a variety of HIV-positive populations. We asked whether additional biomarkers further enhance discrimination. Design and methods: Using patients from VACS for development and from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for validation, we obtained laboratory values from a randomly selected visit from 2000 to 2014, at least 1 year after antiretroviral therapy initiation. Patients were followed for 5-year, all-cause mortality through September 2016. We fitted Cox models with established predictors and added new predictors based on model fit and Harrell's c-statistic. We converted all variables to continuous functional forms and selected the best model (VACS Index 2.0) for validation in ART-CC patients. We compared discrimination using c-statistics and Kaplan–Meier plots. Results: Among 28 390 VACS patients and 12 109 ART-CC patients, 7293 and 722 died, respectively. Nadir CD4+, CD8+, and CD4+ : CD8+ ratio did not improve discrimination. Addition of albumin, white blood count, and BMI, improved c-statistics in VACS from 0.776 to 0.805 and in ART-CC from 0.800 to 0.831. Results were robust in all nine ART-CC cohorts, all lengths of follow-up and all subgroups. Conclusion: VACS Index 2.0, adding albumin, white blood count, and BMI to version 1.0 and using continuous variables, provides improved discrimination and is highly transportable to external settings.

• Publication year

  2019

• Venue

  AIDS (London)

• Publication date

  2019-04-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1097/QAD.0000000000002140PMID 30649058PMCID PMC6749990
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• VACS Index 2.0 uses continuous functional forms and extends the earlier VACS mortality risk index with additional biomarkers for people with HIV.

  Confidence 0.95

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• Nadir CD4+ count, CD8+ count, and the CD4+:CD8+ ratio did not improve discrimination beyond the established predictors.

  Confidence 0.91

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• Adding albumin, white blood count, and body mass index improved model discrimination for 5-year all-cause mortality in both the development and external validation cohorts.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

• albumin

  biomarker, laboratory value

  A routinely measured blood protein used as a clinical biomarker in the mortality prediction model.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• antiretroviral therapy cohort collaboration

  validation cohort, cohort collaboration

  An external multi-cohort HIV dataset used for validating the model beyond the development cohort.

  Aliases: ART-CC

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• body mass index

  biomarker, clinical measure

  A body-size measure calculated from weight and height, included as a clinical predictor in the model.

  Aliases: BMI

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• cd4+:cd8+ ratio

  clinical biomarker, ratio

  The ratio of CD4+ to CD8+ T-cell counts, used as an immune status marker.

  Aliases: CD4/CD8 ratio

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• cd8+ count

  clinical biomarker, laboratory value

  A laboratory measurement of CD8+ T-cell abundance used as a candidate immune marker.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• continuous functional forms

  modeling approach, statistical method

  A modeling approach that keeps predictor variables on a continuous scale rather than converting them to categories.

  Aliases: continuous variables

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• c-statistic

  evaluation metric, discrimination measure

  A summary metric used to quantify how well a model discriminates between outcomes.

  Aliases: Harrell's c-statistic, concordance statistic

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• discrimination

  model property, evaluation concept

  The ability of a prediction model to separate higher-risk from lower-risk patients.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• mortality risk index

  risk score, prediction model

  A composite clinical score designed to estimate the risk of death from available patient data.

  Aliases: mortality prediction score

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• nadir cd4+ count

  clinical biomarker, laboratory value

  The lowest recorded CD4+ T-cell count for a person over the course of HIV care.

  Aliases: lowest CD4+ count

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• vacs index 2.0

  risk score, prediction model

  An updated Veterans Aging Cohort Study mortality risk score for people with HIV that incorporates established variables and added biomarkers.

  Aliases: Veterans Aging Cohort Study Index 2.0, version 2.0 of the VACS Index

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• white blood count

  biomarker, laboratory value

  A blood test measuring the number of white blood cells, used here as a candidate mortality predictor.

  Aliases: WBC, white blood cell count

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

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