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The inflammatory context of HIV infection has been posited to contribute to the higher comorbidity risk noted in HIV-infected populations. One possible pathway may involve 1,25-dihydroxyvitamin D [1,25(OH)(2)D], which plays a wide biologic role in many tissues. We sought to investigate whether inflammation was associated with vitamin D metabolites in a cohort of HIV-infected (HIV+) men receiving treatment and HIV-uninfected (HIV−) men. Vitamin D metabolites, including 25-hydroxyvitamin D [25(OH)D] and 1,25(OH)(2)D, were measured along with 24 inflammatory markers among Multicenter AIDS Cohort Study participants. Exploratory factor analysis reduced inflammatory marker data to a smaller set of inflammatory processes (IPs). Multivariate linear regression was used to evaluate associations between vitamin D metabolites and IPs. There were 466 HIV+ and 100 HIV− men, who contributed 658 stored samples from 1998 to 2008. We found three IPs with IP 1 characterized by sTNF-R2, sIL-2Rα, sCD27, BAFF, sgp130, sCD14, CXCL10 (IP-10), and sIL-6R. While none of the three IPs was associated with 25(OH)D levels in either HIV+ or HIV−, higher levels of IP 1 were significantly associated with the reduced levels of 1,25(OH)(2)D in HIV+, and a similar although nonsignificant trend was seen in HIV−. The association between 1,25(OH)(2)D and inflammation found among HIV-infected men suggests a possible mechanism whereby inflammation leads to the increased comorbidity risk noted among HIV-infected individuals.

Vitamin D may play an important role in a range of disease processes. In the general population, lower vitamin D levels have been associated with kidney dysfunction. HIV-infected populations have a higher risk of chronic kidney disease. Few studies have examined the link between lower vitamin D levels and kidney function decline among HIV-infected persons. We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] with kidney function decline in a cohort of HIV-infected white and black men under highly active antiretroviral therapy treatment in the vitamin D ancillary study of the Multicenter AIDS Cohort Study. The associations of 25(OH)D and 1,25(OH)2D with annual change in estimated glomerular filtration rate (eGFR) were evaluated using linear mixed effects models. This study included 187 whites and 86 blacks with vitamin D measures and eGFR ≥60 ml/min/1.73 m2 at baseline. Over a median follow-up of 8.0 years, lower 25(OH)D levels were significantly associated with faster eGFR decline in whites (adjusted annual change in eGFR, tertile 1: -2.06 ml/min/1.73 m2 vs. tertile 3: -1.23 ml/min/1.73 m2, p trend .03), while no significant association was detected in blacks. Lower 1,25(OH)2D was associated with faster kidney function decline in both whites and blacks, although the estimates were not statistically significant. In conclusion, lower 25(OH)D levels were significantly associated with faster eGFR decline in a cohort of HIV-infected white men, but not in those with black ancestry. Further research is warranted to investigate the association of 25(OH)D and 1,25(OH)2D with kidney function decline in larger and ethnically diverse populations.

Treating cardiovascular disease (CVD) risk factors, including dyslipidemia, is important in HIV care. Low-density lipoprotein cholesterol (LDL-c) target achievement is a readily available benchmark for dyslipidemia control, although use of this target is not uniformly endorsed by professional societies. We examined whether HIV serostatus is associated with not achieving LDL-c target. Among Multicenter AIDS Cohort Study (MACS) participants completing visit 56 (10/1/2011–3/31/2012), we categorized each man as on or off statin therapy and used NCEP ATP III guidelines to determine if each man was at LDL-c target or not at target. We compared proportions of men not at target and determined predictors using multivariate logistic regression. Sixty of 543 (11.1%) HIV-infected men and 87 of 585 (14.9%) HIV-uninfected men not receiving statin therapy were not at target (p=0.07), while 31 of 230 (13.5%) HIV-infected and 29 of 204 (14.2%) HIV-uninfected men receiving statin therapy were not at target (p=0.82). Factors associated with not being at target (among men not receiving statin therapy) included current smoking (OR=2.31, 95% CI 1.31, 4.06) and a diagnosis of hypertension (OR=4.69, 95% CI 2.68, 8.21). Factors associated with not being at target (among men receiving statin therapy) included current smoking (OR=2.72, 95% CI 1.30, 5.67) and diabetes (OR=5.31, 95% CI 2.47, 11.42). HIV-infected and HIV-uninfected men receiving statin therapy demonstrated similar nonachievement of LDL-c targets. Comorbidities (e.g., diabetes) lowered targets and may explain why goals were less likely to be met.

Body fat changes in HIV-infected persons are associated with increased systemic inflammation and increased mortality. It is unknown whether lipodystrophy is also associated with declines in physical function. Between 2001 and 2003, 33 HIV-infected men with evidence of lipodystrophy (LIPO⁺), 23 HIV-infected men without lipodystrophy (LIPO⁻), and 33 seronegative men were recruited from the Multicenter AIDS Cohort Study (MACS) for the Body Composition substudy. Visceral adipose tissue (VAT) was assessed by quantitative computed tomography. Lean body mass (LBM) and extremity fat were measured by dual-energy x-ray absorptiometry. Insulin resistance was estimated by Homeostatic Model Assessment (HOMA). Serum interleukin (IL)-6, soluble tumor necrosis factor (TNF)-α receptors I and II (sTNFRI and sTNFRII), and highly sensitive C-reactive protein (hs-CRP) concentrations were quantified from archived serum samples. These measurements were correlated with grip strength measured in 2007 using linear regression. At the substudy visit, the LIPO⁺ group had higher HOMA, sTNFRI, sTNFRII, and IL-6 levels than the LIPO⁻ group. In 2007, the LIPO⁺ group had lower median grip strength than the LIPO⁻ group (34.4 vs. 42.7 kg, p=0.002). Multivariable analysis of HIV⁺ men showed older age, lower LBM, higher sTNFRII concentrations, and LIPO⁺ status [adjusted mean difference -4.9 kg (p=0.045)] at the substudy visit were independently associated with lower subsequent grip strength. Inflammation, lower LBM, and lipodystrophy in HIV-infected men were associated with lower subsequent grip strength. These findings suggest that inflammation may contribute to declines in functional performance, independent of age.

Chronic kidney disease and HIV infection both independently increase the risk of anemia. It is not known if individuals with both HIV infection and kidney dysfunction are at greater than expected risk of anemia resulting from the combined effect of these factors. Men from the Multicenter AIDS Cohort Study with AIDS-free time after 1996 were included in the analysis if they had an initial hemoglobin value greater than 13 g/dl and available serum creatinine measurements for the estimation of glomerular filtration rate. Hemoglobin data were fit parametrically using a linear mixed effects model and effects of medication use on hemoglobin levels were removed using censoring methods. The effect of both HIV infection and glomerular filtration rate less than 60 ml/min/1.73 m(2) on the mean hemoglobin value was assessed. The risk of having anemia (hemoglobin level falling below 13 g/dl) was estimated. There were 862 HIV-infected and 1,214 HIV-uninfected men who contributed to the analysis. Hemoglobin values across all 17,341 person-visits, adjusting for age, were generally lower in HIV-infected AIDS-free men with impaired kidney function by -0.22 g/dl (95% CI: -0.42, -0.03) compared to men with either HIV infection or impaired kidney function, but not both. HIV-infected AIDS-free men with impaired kidney function have a higher risk of anemia by 1.2% compared to HIV-uninfected men with normal kidney function. Comorbid conditions and medication use did not explain this increase in risk. HIV infection and impaired kidney function have a combined impact on lowering hemoglobin levels, resulting in a higher risk of anemia.