Anemia and HIV in the Antiretroviral Era: Potential Significance of Testosterone.
Authors: Behler Caroline M. , Shade Starley B. , Gregory Kellan , Abrams Donald I. , Volberding Paul A. 
Published: October 2019

Abstract
BACKGROUND: Anemia remains the most common hematologic disorder in human immunodeficiency virus (HIV) infection despite the use of effective antiretroviral therapy, and is associated with decreased quality of life and survival. Hypogonadism is prevalent in advanced HIV disease, however low testosterone levels have not been customarily implicated in HIV-associated anemia. This study was undertaken to determine whether there is a relationship between testosterone levels and androgen use with anemia in HIV, and to characterize other clinical correlates of HIV-associated anemia.
METHODS: This cross-sectional study examined the clinical characteristics of 200 HIV positive patients at a public hospital HIV clinic and clinical features associated with anemia. A written questionnaire detailed previous and current medication use, opportunistic infections and malignancies. Hematologic and virologic parameters, testosterone and erythropoietin levels were measured; CD4 count and viral load nadir and peak levels were obtained from the computerized medical record. Anemia was defined as hemoglobin <13.5 g/dL in men and <11.6 g/dL in women.
RESULTS: Anemia was present in 24% of women and 28% of men. Anemia was negatively associated with female sex (adjusted OR 0.30, 95% CI 0.11–0.85), current antiretroviral therapy (adjusted OR 0.43, 95% CI 0.20–0.95), current androgen use (adjusted OR 0.20, 95% CI 0.05–0.84) and macrocytosis (adjusted OR 0.23, 95% CI 0.09–0.61). Anemia was positively associated with lymphopenia (adjusted OR 4.0, 95% CI 1.36–11.80), high erythropoieitin levels (adjusted OR 7.73, 95% CI 2.92–20.48) and low testosterone levels (adjusted OR 3.27, 95% CI 1.01–10.60).
CONCLUSIONS: Low testosterone levels may have a positive association, and supplemental androgens a negative association with anemia in HIV disease.
Predictors of Anemia
Unadjusted odds ratios and 95% confidence intervals obtained by logistic regression. Variables that achieved a p-value of <0.1 in tests of interaction were included in a multivariable logistic regression model, which was used to obtain adjusted odds ratios and 95% confidence intervals.
N % Anemic Unadjusted OR (95% CI) Adjusted OR (95% CI) Female 38 23.7 0.78 (0.34, 1.78) 0.30 (0.11, 0.85) Male/MTF Transgender 162 28.4 Lymphopenia (<1.0x109/L) 19 57.9 3.05 (1.24, 7.51) 4.00 (1.36, 11.80) Normal Lymphocyte Count 178 24.7 Macrocytosis (MCV>100fL) 71 14.1 0.34 (0.16, 0.74) 0.23 (0.09, 0.61) Normal MCV 117 32.5 Microcytosis (MCV<80fL) 11 63.6 2.91 (0.87, 9.77) 2.02 (0.50, 8.13) Current Antiretroviral Therapy 139 20.1 0.32 (0.17, 0.61) 0.43 (0.20, 0.95) No current Antiretroviral Therapy 61 44.3 Current Androgen Use 23 13.0 0.36 (0.10, 1.27) 0.20 (0.05, 0.84) No Current Androgen Use 171 28.7 EPO x Testosterone Interaction High EPO-High/nl Testosterone 46 41.3 2.50 (1.23, 5.11) 7.73 (2.92, 20.48) Low/nl EPO-Low Testosterone 24 37.5 2.39 (0.89, 6.39) 3.27 (1.01, 10.60) High EPO-Low Testosterone 11 27.3 0.33 (0.04, 2.50) 0.17 (0.012, 2.36) Low/nl EPO-High/nl Testosterone 115 20.9