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Gait speed declines at a faster rate in persons with HIV (PWH) than in the general population but the risk factors associated with this decline are not well understood. In the AIDS Clinical Trials Group (ACTG) A5322 (HAILO, HIV Infection, Aging, and Immune Function Long-term Observational Study), an observational cohort study of PWH ≥40 years of age, those who developed slow gait during the first 3 years of follow-up were compared with persons who maintained normal speed. Associations with demographic and clinical covariates were assessed using multivariable logistic regression. Of 929 participants, 81% were men, 31% Black, and 20% Hispanic. Median age was 51 years [interquartile range (IQR) = 46-56]. At study entry, 92% had plasma HIV RNA <50 copies/mL with median CD4 count 631 cells/mm 3 (IQR = 458-840). At study entry, 7% of participants had slow gait, 16% had neurocognitive impairment (NCI), and 12% had diabetes. Over 3 years, 87% maintained normal gait speed, 3% maintained a slow gait, 6% developed a slow gait, and 4% improved from slow to normal gait speed. In multivariable models, hemoglobin A1C (HbA1C) percentage, per one unit increase [odds ratio (OR) = 1.36; 95% confidence interval (CI) = 1.03-1.81; p  = .033], NCI (OR = 3.47; 95% CI = 1.57-7.69 p  = .002), and black versus white race (OR = 2.45; 95% CI = 1.08-5.59; p  = .032) at entry were significantly associated with development of slow gait compared with those maintaining normal gait speed. The association between baseline HbA1C and development of slow gait speed highlights an intervenable target to prevent progression of physical function limitations.

HIV-infected men have increased rates of osteoporosis and fracture compared to HIV-uninfected men. Testosterone use among HIV-infected men is common. In HIV-uninfected men, testosterone increases bone mineral density (BMD), but its effects have not been evaluated in HIV-infected men. In a substudy of Multicenter AIDS Cohort Study (MACS), the Bone Strength Substudy (BOSS) enrolled 202 HIV-infected and 201 HIV-uninfected men aged between 50 and 69 years. Study participants underwent dual-energy X-ray absorptiometry (DXA) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and detailed assessment of osteoporosis risk factors. We used multivariable linear regression to determine associations and 95% confidence intervals (CIs) between self-reported testosterone use and T-scores at the LS, TH, and FN after adjustment for demographics, behavioral covariates, comorbidities, and other traditional osteoporosis risk factors. HIV-infected men reported more frequent testosterone use (22% vs. 4%; p < .001) and had lower median BMD T-score at TH than HIV-uninfected men (0.0 vs. 0.3; p = .045) but similar T-scores at LS and FN. In the overall study population, testosterone use was associated with significantly greater BMD T-score at LS (0.68; 95% CI: 0.22-1.13). In HIV-infected men with virologic suppression, testosterone was significantly associated with higher BMD T-score at LS (0.95; 95% CI: 0.36-1.54) and TH (0.45; 95% CI: 0.04-0.86). Current testosterone use is common in HIV-infected men and was associated with higher BMD, compared to those not taking testosterone. Testosterone's role in reducing fracture risk in HIV-infected men should be investigated.

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.

Maximizing the rates of virologic suppression (VS) among gay, bisexual, and other men who have sex with men (MSM) is essential to limiting HIV morbidity and sexual transmission of HIV in the United States. We analyzed data for MSM of non-Hispanic white (white), non-Hispanic black (black), or Hispanic/Latino race/ethnicity in the HIV Outpatient Study (HOPS) at nine U.S. HIV clinics. VS (HIV RNA <50 copies/ml) was measured closest to January 1, 2015. We modeled factors associated with VS among persons prescribed antiretroviral therapy (ART) for ≥6 months and assessed VS for a subset of participants with behavioral interview data. Among 1,303 MSM studied, 24% were black and 11% were Hispanic/Latino. Fewer black than white or Hispanic/Latino MSM had any documented ART use history (92% vs. 99% and 94%, respectively), and fewer had VS (72% vs. 91% and 81%), p  < .001. In analyses of MSM prescribed ART, which adjusted for insurance type, duration of ART use, and CD4 + cell count, blacks had lower prevalence of VS than whites [adjusted prevalence ratio (PR) 0.87, confidence interval (95% CI) 0.81-0.93] and Hispanics/Latinos did not (PR 0.95, 95% CI 0.88-1.02). Among 331 MSM with interview data, 6% had no VS, but reported anal sex without a condom with an HIV-uninfected or unknown HIV serostatus male partner in the past 6 months. In this study of HIV-infected MSM, blacks had a significantly lower prevalence of VS than white men. Optimizing HIV care and prevention among all MSM will require addressing underlying risk factors and social determinants of health that contribute to racial/ethnic disparities in HIV outcomes.

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) 2 D] 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) 2 D 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 m 2 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 m 2 vs. tertile 3: -1.23 ml/min/1.73 m 2 , p trend .03), while no significant association was detected in blacks. Lower 1,25(OH) 2 D 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) 2 D with kidney function decline in larger and ethnically diverse populations.

We evaluated associations of serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) levels in a cohort of HIV-infected and HIV-uninfected men at risk for infection in the United States. Stored samples collected between 1999 and 2008 were tested for vitamin D metabolites between 2014 and 2015. Vitamin D deficiency was defined as a serum concentration of 25[OH]D <20 ng/ml. Multivariate models were used to assess associations of various demographic and clinical factors with vitamin D status. HIV-infected men on effective antiretroviral therapy (n = 640) and HIV-uninfected men (n = 99) had comparable levels of 25[OH]D and 1,25[OH] 2 D, and prevalences of vitamin D deficiency were 41% in HIV-infected and 44% in HIV-uninfected men, respectively. Self-reported black or other non-white race, obesity, and normal kidney function were significant predictors of vitamin D deficiency regardless of HIV serostatus. Lower CD4 + T cell count was associated with vitamin D deficiency in HIV-infected men, while current ritonavir use was protective. Self-reported black race was the only factor significantly associated with higher levels of 1,25[OH] 2 D (vs. whites; β = 4.85 pg/ml, p = .003). Levels of 1,25[OH] 2 D and 25[OH]D were positively correlated in HIV-infected men (β = 0.32 pg/ml, p < .001), but not in uninfected men (β = -0.09 pg/ml, p = .623; p < .05 for interaction). Vitamin D deficiency was prevalent regardless of HIV serostatus in this cohort, suggesting that HIV infection did not confer additional risk of deficiency in this cohort of well-treated HIV-infected men. However, HIV infection and race may have implications for vitamin D metabolism and 1,25[OH] 2 D levels.

HIV is a pandemic disease, and many cellular and systemic factors are known to alter its infectivity and replication. Earlier studies had suggested that anemia is common in HIV-infected patients; however, higher iron was also observed in AIDS patients prior to the introduction of antiretroviral therapy (ART). Therefore, the relationship between iron and viral infection is not well delineated. To address this issue, we altered the levels of cellular iron in primary CD4(+) T cells and showed that higher iron is associated with increased HIV infection and replication. In addition, HIV infection alone leads to increased cellular iron, and several ART drugs increase cellular iron independent of HIV infection. Finally, HIV infection is associated with increased serum iron in HIV-positive patients regardless of treatment with ART. These results establish a relationship between iron and HIV infection and suggest that iron homeostasis may be a viable therapeutic target for HIV.