Identifying individuals with virologic failure after initiating effective antiretroviral therapy: The surprising value of mean corpuscular hemoglobin in a cross-sectional study

We included individuals followed within the Johns Hopkins HIV Clinical Cohort who initiated antiretroviral therapy and had concurrent HIV RNA and biomarker measurements ≥4 months after HAART. A two tiered approach to determine whether clinical markers could improve prediction included: 1) identification of predictors of HIV RNA levels >500 copies/ml and 2) construction and validation of a prediction model.Three markers (mean corpuscular hemoglobin [MCH], CD4, and change in percent CD4 from pre-HAART levels) in addition to the change in MCH from pre-HAART levels contained the most predictive information for identifying an HIV RNA >500 copies/ml. However, MCH and change in MCH were the two most predictive followed by CD4 and change in percent CD4. The logistic prediction model in the validation data had an area under the receiver operating characteristic curve of 0.85, and a sensitivity and specificity of 0.74 (95% CI: 0.69-0.79) and 0.89 (95% CI: 0.86-0.91), respectively.Immunologic criteria have been shown to be a poor guideline for identifying individuals with high HIV RNA levels. MCH and change in MCH were the strongest predictors of HIV RNA levels >500. When combined with CD4 and percent CD4 as covariates in a model, a high level of discrimination between those with and without HIV RNA levels >500 was obtained. These data suggest an unexplored relationship between HIV RNA and MCH.Current World Health Organization guidelines recommend using CD4 counts to monitor treatment response to highly active antiretroviral therapy (HAART) in regions where HIV viral load testing is unavailable [1]. However, recent reports suggest that monitoring CD4 counts does not accurately classify individuals who have not successfully suppressed HIV RNA levels [2-4]. One study, from Uganda, examined whether CD4 counts and CD4 percentages could be used to classify individuals as above or below four thresholds of HIV RNA (50, 500, 1000, and 5000) and at three time points (6, 12, and 18 mont