Abstract
Background: Sex hormone-binding globulin (SHBG) is a glycoprotein that regulates the bioavailability of sex hormones, may directly affect glucose metabolism, and increases with age in the general population. SHBG concentrations are higher in people with HIV, a population in whom accelerated aging has been hypothesized. It is unclear whether age-related trajectories of SHBG differ by HIV serostatus. Methods: SHBG was measured in 182 men with HIV (MWH) and 267 men without HIV (MW/oH) from the Multicenter AIDS Cohort Study (MACS) in four U.S. cities, who had ≥2 samples over a 10 year period. Outcome measure: SHBG, log2SHBG. Multivariable linear mixed-effects regression models were used to evaluate whether SHBG (log2-transformed) and its rate of change differed by HIV serostatus after adjustment for covariates: age, race, BMI, smoking, education, hepatitis C virus infection, total testosterone concentrations, time of day of blood drawn and comorbidities (history of diabetes, kidney disease, liver disease, cancer, depression, hypertension) Results: At baseline, mean age among MWH was similar to MW/oH (51±5 vs 49±6 years). However, SHBG values were higher in MWH compared to MWo/H (65.6±48.8 nmol/L vs. 45.4±22 nmol/L, p<0.001). The rate of SHBG change with age was (1.021 (95% CI:1.010-1.028) or 2.1% per year in MWH and (1.014 nmol/L/year (95% CI:1.010-1.019) or 1.4% per year in MW/oH, p=0.05 for difference in slopes. Among MWH, higher SHBG levels were significantly associated with lower CD4+ T cell count (0.99 (5%CI:0.98-1.00), p<0.05), fewer cumulative years on zidovudine (0.98 nmol/L (95%CI:0.96,1.00), p<0.001) and greater cumulative years on non-nucleoside reverse transcriptase inhibitors drugs (1.02 (95%CI:1.00,1.04), p<0.05). Conclusion: Aging-related increases in SHBG were greater in magnitude among men with HIV and were related to poorer immunologic status and antiretroviral factors. The mechanisms and consequences of these findings require further investigation.
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