Allison Ross Eckard

Few studies have evaluated habitual nutrient intake among HIV-infected youth in the United States, even though diet may influence disease progression and risk of comorbidities. This study determined habitual micronutrient and macronutrient intake in HIV-infected youth. HIV-infected subjects and healthy controls 1–25 years old were prospectively enrolled. Nutrient intake was assessed via 24-h dietary recalls performed every 3 months for 1 year and compared to recommended intake from the U.S. Dietary Reference Intakes (DRIs) and Acceptable Macronutrient Distribution Ranges (AMDRs). Subjects with two or more food recalls were analyzed (175 HIV ⁺ and 43 healthy controls). Groups were similar in age, race, sex, body mass index, and kilocalorie intake. In both groups, intake of several micronutrients was below the DRI. In addition, HIV ⁺ subjects had a lower percentage DRI than controls for vitamins A, D, E, pantothenic acid, magnesium, calcium, folate, and potassium. HIV ⁺ subjects' percentage caloric intake from fat was above the AMDR and was higher than controls. Caloric intake was negatively correlated with current and nadir CD4 count. Zinc, riboflavin, and magnesium percentage DRI were positively associated with current CD4 count. In HIV ⁺ subjects not on antiretroviral therapy, HIV-1 RNA levels were negatively correlated with protein intake. HIV ⁺ youth have an inadequate dietary intake of several essential nutrients and poorer dietary intake compared to controls. Intake of some nutrients was associated with important HIV-related factors. Further investigation is warranted to determine the impact of dietary intake of specific nutrients on HIV progression and chronic complication risk in this population.

Antimicrobial peptide LL-37 is produced in response to active vitamin D to exert immunomodulatory effects and inhibits HIV replication in vitro. To date, no studies have investigated LL-37 in HIV-infected patients. This study sought to investigate LL-37 and the relationship to 25-hydroxyvitamin D [25(OH)D] and HIV-related variables in this population. HIV-infected subjects and healthy controls ages 1-25 years old were prospectively enrolled in this cross-sectional study. Fasting plasma LL-37 and 25(OH)D concentrations were measured in duplicate with ELISA. HIV(+) subjects (36 antiretroviral therapy (ART)-experienced subjects; 27 ART-naïve subjects) and 31 healthy controls were enrolled. Overall, 93% were black and the median age was 20 years. There was no difference in median (interquartile range) LL-37 between the HIV-infected group and controls [58.3 (46.4,69.5) vs. 51.3 (40.8,98.2) ng/ml, respectively; p=0.57]; however, the ART-experienced group had higher concentrations than the ART-naive group [66.2 (55.4,77.0) vs. 48.9 (38.9,57.9) ng/ml, respectively; p<0.001]. LL-37 was positively correlated with 25(OH)D in controls, but not in HIV-infected groups, and was positively correlated with current CD4 and ΔCD4 (current-nadir) in the ART-experienced group. After adjustment for age, race, sex, and HIV duration, the association between LL-37 and CD4 remained significant. These findings suggest that HIV and/or HIV-related variables may alter the expected positive relationship between vitamin D and LL-37 and should be further investigated.

Although patients with HIV infection are living decades longer than before with the advent of combination antiretroviral therapy, they have an increased rate of co-morbidities associated with chronic HIV, such as osteoporosis, cardiovascular disease, and immune dysfunction. Many of these complications are known to be affected by vitamin D status in the general population. Thus, the high rate of vitamin D deficiency among HIV-infected patients is alarming. Many observational and cohort studies have demonstrated that vitamin D deficiency is associated with these HIV-related complications, but randomized, placebo-controlled trials are limited. This paper reviews recent data on vitamin D deficiency in HIV infection.

Vitamin D deficiency is common in HIV-infected populations. In resource-limited settings, vitamin D deficiency has been shown to affect HIV disease progression and mortality in pregnant women, and also increases mother-to-child HIV transmission and mortality in their infants. This study sought to investigate vitamin D status in HIV-infected women compared to healthy controls in a high-income country setting and determine variables associated with vitamin D deficiency. We prospectively enrolled 40 women/infant pairs (16 HIV-infected women/HIV-exposed infant pairs and 24 uninfected/unexposed pairs). In serum cord blood, 25-hydroxyvitamin D [25(OH)D] concentrations were suboptimal (<30 ng/ml) in 100% of subjects from both groups. White race, non-Hispanic ethnicity was the only variable associated with higher serum 25(OH)D concentrations. This high prevalence of vitamin D deficiency, especially among HIV-infected women and their infants, deserves further investigation, as it may have a negative impact on maternal and infant health.

Objectives: Thiazoledinediones increase limb fat in HIV+ patients with lipoatrophy. However, their use in the general population has been associated with bone loss and fracture. We sought to determine the effects of rosiglitazone on bone metabolism in HIV-infected patients. Methods: HIV+ patients with lipoatrophy were randomized to rosiglitazone versus placebo for 48 weeks in a double-blind, placebo-controlled trial. Limb fat, bone mineral density (BMD), bone formation markers (procollagen type 1 amino-terminal propeptide [P1NP], osteocalcin [OC]) and bone resorption markers (C-terminal telopeptide of type I collagen [CTX]) were measured, along with receptor activator for nuclear factor kappa β ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines. Results: Seventy-one subjects were randomized to rosiglitazone or placebo: 17% female and 51% white. Total BMD did not change significantly in either group. In the rosiglitazone group, P1NP showed statistically significant decreases at 24 and 48 weeks; however, changes compared to placebo were only significant at 24 weeks. OC decreased significantly in the rosiglitazone group at 24 weeks, but there were no between-group differences. CTX, RANKL, or OPG did not change for either group. Multivariable regression within the rosiglitazone arm showed P1NP changes were inversely associated with limb fat changes, protease inhibitors, and tenofovir use. Conclusion: Rosiglitazone use was associated with decreased bone formation, but it did not alter bone resorption or total BMD. The increase in limb fat that accompanies rosiglitazone use appears to be associated with decreased osteoblast activity. Further studies are needed to determine the effect of thiazoledinediones on bone health in HIV-infected persons.

HIV-infected patients are at increased risk of cardiovascular disease (CVD). This study assessed longitudinal changes in carotid intima-media thickness (cIMT) as a surrogate marker for CVD, and determined the relationship between cIMT and cardiovascular risk factors in HIV-infected children/young adults. This was a longitudinal, observational study comparing cIMT, fasting metabolic profile, and C-reactive protein in HIV-infected subjects 2 to 21 years old to matched controls at baseline and 48 weeks. Thirty-five HIV+ subjects and 37 controls were included in the analysis. Among HIV+ subjects, the median age was 10 years, body mass index was 18.7 kg/m2, 37% were male, CD4 count was 32%, 77% had HIV-RNA <400 copies/mL, and 86% were on antiretrovirals. At baseline, HIV+ had higher lipids and C-reactive protein. HIV-infected had higher internal carotid artery (ICA) and common carotid artery (CCA) IMT (mm) (ICA: HIV+, 0.90; controls, 0.78 [P = 0.01]; CCA: HIV+, 1.00; controls, 0.95 [P = 0.05]). At 48 weeks, CD4% increased and low-density lipoprotein decreased in HIV-infected subjects. ICA and CCA median changes for HIV-infected subjects were −0.23 and −0.15 mm, respectively (both P < 0.01). In controls, only CCA changed (P = 0.04). Between-group changes were not significant, except when only 31 perinatally infected HIV+ subjects and the controls were compared (CCA P = 0.04). In multiple regression analyses of HIV+ subjects, antiretroviral therapy duration and CD4% were associated with cIMT changes. Higher cIMT was found in HIV-infected subjects than in healthy controls, but at 48 weeks, cIMT was similar between groups. These data suggest that HIV-infected children/young adults are at high risk of CVD, but lipid control, immune restoration, and viral suppression with continuous antiretroviral therapy may prevent its worsening.

Background: Patients with HIV infection are at increased risk of cardiovascular disease (CVD). Vitamin D insufficiency has been associated with increased CVD risk in non-HIV populations. This study sought to determine the relationship between vitamin D status and markers of CVD and HIV-related factors in HIV-positive patients. Methods: Patients with HIV infection on antiretroviral therapy and healthy controls were prospectively enrolled. Fasting lipids, glucose, insulin, inflammatory markers (soluble tumour necrosis factor-α receptor I, interleukin-6 and high-sensitivity C-reactive protein) and endothelial markers (soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1) were measured. Fasting 25-hydroxyvitamin D (25(OH)D) was measured from stored serum samples. The internal carotid artery and common carotid artery (CCA) intima-media thickness (IMT) were measured in a subset of HIV-positive patients. Baseline cross-sectional data were analysed. Results: A total of 149 HIV-positive patients (56 with carotid IMT) and 34 controls were included. Controls had higher adjusted mean 25(OH)D levels than HIV-positive patients ( P=0.02). In multivariable linear regression among the HIV-positive patients, 25(OH)D was positively associated with CD4 ⁺ T-cell restoration after antiretroviral therapy (ΔCD4 = current - nadir CD4 ⁺ T-cell; P<0.01), but was not associated with inflammatory or endothelial markers. In multivariable logistic regression, odds of having CCA IMT above the median were more than 10x higher in those with lower 25(OH)D levels (OR=10.62, 95% CI 1.37-82.34; P<0.01). Conclusions: Vitamin D status in HIV-positive patients was positively associated with improved immune restoration after antiretroviral therapy and negatively associated with CCA IMT. These findings suggest that vitamin D may play a role in HIV-related CVD and in immune reconstitution after antiretroviral therapy.