Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy.

BACKGROUND: A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is a naturally synthesized hormone, with important immunomodulatory functions. In the general population, its deficit has been associated with increased markers of inflammation. Vitamin D deficit may therefore play a role in the establishment of elevated systemic immune activation, which persists despite suppressive antiretroviral therapy (ART) in HIV-infected patients, and is predictive of disease progression; and vitamin D supplementation may be beneficial in this context. METHODS: We performed both a cross-sectional study (vitamin D deficit versus normal level) and a longitudinal study (upon vitamin D supplementation for 6 to 12 months) of HIV-1-infected patients receiving suppressive ART. The primary outcome measure was the percentage of activated memory CD8(+) T cells in blood, which is a robust marker associated with disease progression. Secondary outcomes included general T-lymphocyte and B-lymphocyte phenotype. RESULTS: Although vitamin D deficiency had no influence on T-cell and B-cell subset distribution, we found an association between vitamin D and immune activation levels in HIV-1-infected patients. Vitamin D supplementation in vitamin D-deficient patients resulted in reduced immune activation levels. CONCLUSION: The present data support the rationale of vitamin D supplementation in the routine clinical management of HIV-1-infected patients, in order to decrease immune activation levels and possibly improve long-term survival.

Role of vitamin D in acquired immune and autoimmune diseases.

Vitamin D has been attributed roles in the pathogenesis and prevention of several diseases such as cancer, cardiovascular disease, multiple sclerosis, diabetes, autism and autoimmune diseases. The concomitant expression of the 25-hydroxyvitamin D3-1α-hydroxylase and of the vitamin D3 receptor in animal and human tissues and organs other than bone supports this paradigm. Translated into the clinical field, meta-analyses and systematic reviews have also revealed an association between vitamin D insufficiency or deficiency and non-osseous diseases. Although relying on the large databases, they are diverse in nature and involve participants of varying age and evolving in different environments. Furthermore, they do not allow any analysis of a possible causal relationship between vitamin D supplementation and clinical outcomes. Following a brief historical account, this review addresses these caveats, and gives examples of randomized controlled trials conducted in the fields of acquired immune and autoimmune diseases.

HIV-1 DNA levels in peripheral blood mononuclear cells and cannabis use are associated with intermittent HIV shedding in semen of men who have sex with men on successful antiretroviral regimens.

BACKGROUND: Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. METHODS: HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. RESULTS: In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. CONCLUSION: We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART.

Prognostic value of vitamin D level for all-cause mortality, and association with inflammatory markers, in HIV-infected persons.

BACKGROUND: Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. METHODS: Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. RESULTS: In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). CONCLUSIONS: Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.

[Vitamin D and infectious diseases]. / Vitamine D et infections.

Vitamin D plays a role in the synthesis of antibacterial peptids and in autophagy. Several studies have shown that low levels of vitamin D are associated with the susceptibility and the severity of acute infections on one hand, and with an unfavorable outcome of some chronic infections (such as HIV infection). Vitamin D supplementation improves response to treatment of some viral (such as chronic hepatitis C infection) or bacterial infections (such as pulmonar tuberculosis). Vitamin D supplementation demonstrated no benefit in reducing the incidence of pulmonary infections. The target level of vitamin D to be reached after supplementation is not known yet.

Vitamin D3 supplementation scheme in HIV-infected patients based upon pharmacokinetic modelling of 25-hydroxycholecalciferol.

AIMS: Vitamin D deficiency is prevalent in HIV-infected patients and has been associated with osteopenia and HIV disease progression. Our aims were to investigate the pharmacokinetics of 25-hydroxycholecalciferol [25(OH)D], the effect of antiretroviral treatment (ARV) and others factors that may influence the pharmacokinetics, and to determine a vitamin D3 dosing scheme to reach the 30 ng ml(-1) threshold (defined as 25(OH)D sufficiency). METHODS: This monocentric retrospective study included 422 HIV-infected patients aged 16 to 85 years. A total of 723 25(OH)D concentrations were available for pharmacokinetic evaluation and a population pharmacokinetic model was developed with MONOLIX 3.2. RESULTS: Median 25(OH)D at baseline was 16 ng ml(-1) (interquartile range 11-23 ng ml(-1)) for the total population, 17% of patient had concentrations below 10 ng ml(-1), 68% between 10 and 30 ng ml(-1) and 15% above 30 ng ml(-1). 25(OH)D pharmacokinetics were best described by a one compartment model with an additional endogenous production. The effects of season and skin phototype were significant on production rate. The endogenous production was 20% lower in non-white skin phototype patients and was decreased by 16% during autumn, winter and spring. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs (ARV). To obtain concentrations between 30 and 80 ng ml(-1), the dosing recommendation was 100,000 IU every month. CONCLUSIONS: Season and skin phototype had an influence on the endogenous production of 25(OH)D. However no effect of ARV was found. A dosing scheme to reach sufficient 25(OH)D concentrations is proposed.

Selection of a rare resistance profile in an HIV-1-infected patient exhibiting a failure to an antiretroviral regimen including tenofovir DF.

The human immunodeficiency virus type 1 (HIV-1) resistance profile, K65R, K70E and M184V, on reverse transcriptase gene was associated with the virologic rebound consecutively to the switch of lopinavir/r to tenofovir DF in a stable regimen with nucleoside backbone of abacavir, lamivudine and didanosine. The high selective pressure on the same resistance pathway was probably associated with the loss of antiviral potency, even in well-controlled patient.