Effect of High-Dose Vitamin D3 in Smokers and Non-Smokers With and Without HIV

Effect of High-Dose Vitamin D3 on Alveolar Macrophage Function, LL-37, and Oxidative Stress in Smokers and Non-Smokers With and Without HIV

Supplementation with vitamin D improves HIV+ macrophages phagocytosis in vitro. There is evidence to suggest that administering vitamin D can in fact improve immune function in individuals. The study will evaluate the impact of high dose vitamin D in HIV+ smokers' and HIV- smokers' in vivo. The primary goal is to improve innate immune host response to infection in patients already at high risk by virtue of HIV and smoking status.

Tobacco smoke suppresses the lung's ability to fight infection. Smoking is three times more prevalent in the HIV+ compared to HIV- patients. Viral load was found to be significantly increased in HIV+ smokers compared to HIV+ non-smokers, suggesting that smoking enhances HIV-1 viral replication in macrophages, which contributes to disease progression. Vitamin D deficiency has been associated with increased mortality in HIV+ persons, but there is limited research on how this is impacting the health of these highest risk patients and if aggressive repletion with vitamin D can improve overall health.The study team hypothesizes that vitamin D administration will increase pathogen clearance and improve innate immune function. The proposed pre and post interventional study is designed to characterize alveolar macrophage function and lung immunity according to tobacco use and HIV status, and determine the impact of high dose oral vitamin D3 on AM phagocytic function and innate immunity.

Difference in alveolar macrophage (AM) phagocytic index between HIV+ smokers compared to HIV- non-smokers.

A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.

Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in phagocytosis percent positive between HIV+ smokers compared to HIV- non-smokers will be calculated.

A phagocytic index will be determined by challenging AM isolated from bronchoalveolar lavage (BAL) to Staph. Aureus in vitro.

Difference in total and free vitamin D (25(OH) D) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in total and free 25(OH) D between HIV+ smokers compared to HIV- non-smokers will be measure by ELISA (enzyme-linked immunosorbent assay) levels.

Difference in peptide LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in an antimicrobial and immunostimulating/-modulating peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.

Difference in tumor necrosis factor alpha (TNF-α) between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in tumor necrosis factor alpha (TNF-α) - cytokine involved in systemic inflammation - between HIV+ smokers compared to HIV- non-smokers will be calculated .

Difference in messenger ribonucleic acid (mRNA) expression of LL-37 between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in mRNA expression of antimicrobial peptide LL-37 between HIV+ smokers compared to HIV- non-smokers will be calculated.

Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers, prior to vitamin D administration.

Difference in alveolar oxidative stress between HIV+ smokers compared to HIV- non-smokers will be measured using AM isolated from bronchoalveolar lavage (BAL) .

Difference in total and free vitamin D (25(OH) D) will be measure by ELISA (enzyme-linked immunosorbent assay)

Difference in alveolar oxidative stress will be measured using AM isolated from bronchoalveolar lavage (BAL) .

Inclusion Criteria: Subjects living with HIV-1 infection who have been on anti-retroviral therapy (ART) for a minimum of 12 months and are followed longitudinally for their HIV healthcare; Ability to give informed consent. Exclusion Criteria: Age <18 yrs old; Known or possible pregnancy or breastfeeding; Documented history of cirrhosis or a direct bilirubin ≥ 2.0 mg/dL; Documentation of left ventricular ejection fraction < 40% or myocardial infarction within the past 6 months; End-stage renal disease requiring dialysis or a serum creatinine ≥ 2 mg/d; Spirometry with forced vital capacity (FVC) or forced expiratory volume (FEV1)< 70% of predicted value; Bleeding disorders such as thrombocytopenia or significant gastrointestinal bleeding within the past year; Inability to undergo bronchoscopy safely; High risk behaviors without known HIV status.