25-hydroxyvitamin D, influenza vaccine response and healthcare encounters among a young adult population.

BACKGROUND: Influenza causes significant morbidity and mortality; the pandemic in 2009-2010 was a reminder of the potential for novel strains and antigenic changes. Studies have shown that vitamin D deficiency may be associated with poor vaccine immunogenicity, therefore we sought to determine if there was a correlation between 25-hydroxyvitamin D [25(OH)D] and influenza vaccine response. METHODS: A retrospective observational study was conducted among young, healthy military members to evaluate the association between total 25(OH)D levels with post influenza vaccination antibody titers and healthcare encounters during the 2009-10 influenza season. Univariate analyses were performed to evaluate whether 25(OH)D levels are associated with baseline characteristics and post-vaccination antibody responses. Multivariable logistic regression models were utilized to determine the associations between antibody responses and 25(OH)D levels adjusting for possible confounders. RESULTS: A total of 437 subjects were studied. Most participants were young adults (91% were 18-39 years of age), 50% were male, and 56% resided in the southern U.S. Overall, 152 (34.8%) were vitamin D deficient, 167 (38.2%) insufficient, and 118 (27.0%) with normal 25(OH)D levels. There were no demographic differences by 25(OH)D category. Only 224 (51.3%) demonstrated a seroprotective anti-influenza post-vaccination titer, which did not vary by categorical 25(OH)D levels [vitamin D deficient vs. normal: OR 1.10 (0.68-1.78) and insufficient vs. normal: OR 1.25 (0.78-2.01)] or continuous vitamin D levels [OR 0.98 (0.84-1.15)]. There were also no associations with increased influenza like illnesses, respiratory diagnoses and healthcare encounters between the vitamin D groups. CONCLUSION: Vitamin D insufficiency and deficiency were highly prevalent despite evaluating a young, healthy adult population. There were no significant associations between 25(OH)D levels and post-vaccination antibody titers to influenza vaccine. Further studies are required to discover strategies to improve vaccine efficacy as well as to determine the role of 25(OH)D in vaccine immunity.

Vitamin D levels and influenza vaccine immunogenicity among HIV-infected and HIV-uninfected adults.

BACKGROUND: Vaccination is the most important preventive strategy against influenza, however post-vaccination antibody responses are often inadequate especially among HIV-infected persons. Vitamin D deficiency has been suggested to adversely influence immune responses and is highly prevalent among HIV-infected adults. Therefore, we evaluated the association between 25-hydroxyvitamin D [25(OH)D] levels and post-influenza vaccination responses. METHODS: We conducted a prospective cohort study evaluating the immunogenicity of monovalent influenza A (H1N1) vaccination among both HIV-infected and HIV-uninfected adults (18-50years of age) during the 2009-2010 influenza season. Antibody titers were evaluated at baseline, day 28, and 6months post-vaccination using hemagluttination inhibition assays. Serum 25(OH)D levels were measured at day 28. Univariate and multivariate regression analyses examined the association between 25(OH)D levels [categorized as <20ng/ml (deficiency) vs. ⩾20ng/ml] with the primary outcome of seroconversion. Secondary outcomes included seroprotection; a ⩾4-fold increase in titers; and geometric mean titers post-vaccination. Analyses were repeated using 25(OH)D levels as a continuous variable. RESULTS: A total of 128 adults [64 HIV-infected (median CD4 count 580cells/mm(3)) and 64 HIV-uninfected] were included. Seroconversion at day 28 post-vaccination was achieved in fewer HIV-infected participants compared with HIV-uninfected participants (56% vs. 74%, p=0.03). Vitamin D deficiency was more prevalent among HIV-infected persons vs. HIV-uninfected persons (25% vs. 17%), although not significantly different (p=0.39). There were no associations found between lower 25(OH)D levels and poorer antibody responses at day 28 or 6months for any of the study outcomes among either HIV-infected or HIV-uninfected adults. CONCLUSION: Vitamin D deficiency was common among both HIV-infected and HIV-uninfected adults, but lower levels did not predict antibody responses after H1N1 (2009) influenza vaccination. Low 25(OH)D levels do not explain poorer post-vaccination responses among HIV-infected persons.

Treatment of high-level gentamicin-resistant Enterococcus faecalis endocarditis with daptomycin plus ceftaroline.

A recurrent case of left-sided endocarditis caused by high-level aminoglycoside-resistant Enterococcus faecalis was successfully treated with ceftaroline and daptomycin. This combination demonstrated excellent synergy in vitro. Mechanistically, ceftaroline enhanced binding of daptomycin to the cell membrane and sensitized E. faecalis to killing by human cathelicidin LL-37, a cationic innate host defense peptide. Daptomycin plus ceftaroline may be considered in salvage therapy in E. faecalis endovascular infections and requires further study.

High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial.

BACKGROUND: 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4-6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log(10) decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4(+) and CD8(+) T cells was used to measure immune activation. RESULTS: Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (-0.13 log(10) copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4(+) HLA-DR(+) (-2.5%; P = .02), CD8(+) HLA-DR(+) (-5%; P = .006), and CD8(+) HLA-DR(+) CD38(+) T cells (-3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol. CONCLUSIONS: Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes.