Biomarkers to monitor safety in people on art and risk of mortality

Abstract

Introduction: Though patients with HIV now have near normal life expectancies as a result of antiretroviral treatment, long-term adverse effects are of growing concern. Using time-updated laboratory measurements, we use several methods to derive a score that can be used to identify individuals at high risk of mortality.

Methods: Patients who started highly active antiretroviral therapy after 2000 and had ≥1 CD4 count, viral load, and laboratory marker recorded after the date of starting highly active antiretroviral therapy were included in the analyses. Laboratory markers were stratified into quintiles and associations between each marker and mortality was assessed using Poisson regression. The estimates of the final model were used to construct a score for predicting short-term mortality. Several methods, including multiple imputation, were used for analyzing records with missing measurements.

Results: Of the 7232 patients included in this analysis, 247 died over 24,796 person-years of follow-up, giving an overall mortality rate of 1.00 (95% confidence interval: 0.87 to 1.12) per 100 person-years. Regardless of which method was used to deal with missing data, albumin, alkaline phosphatase, and hemoglobin were independently associated with mortality. Alanine transaminase was independently associated with mortality when patients with missing measurements were assumed to have measurements within the normal range. The C-statistics for all models ranged from 0.76 to 0.78.

Conclusion: Measures of alanine transaminase, albumin, alkaline phosphatase, and hemoglobin in the normal range were predictive of mortality, and hence we suggest using a scoring system to predict mortality which relies on the raw values of these 4 laboratory markers.