1.
Vitamin D status and associated factors among HIV-infected children and adolescents on antiretroviral therapy in Kampala, Uganda.
Piloya, TW, Bakeera-Kitaka, S, Kisitu, GP, Idro, R, Cusick, SE
PloS one. 2021;(6):e0253689
Abstract
BACKGROUND A high prevalence of suboptimal serum vitamin D has been reported among HIV infected children even in countries with high sunshine abundance throughout the year. Vitamin D is a potent immune modulator of innate and adaptive immune responses. Vitamin D regulates immune responses through the vitamin D receptor on CD4 cells. We aimed to determine the vitamin D status of HIV infected children and factors associated with suboptimal vitamin D. METHODS This was a cross sectional study. We enrolled children aged between 6 months and 12 years attending an outpatient paediatric HIV clinic. Serum 25-hydroxyvitamin D (25(OH)D) was measured using the electrochemoluminisence method. Suboptimal vitamin D was defined as 25(OH)D <30 ng/ml, vitamin D insufficiency and deficiency were 21-29 ng/ml and <20 ng/ml respectively. Anthropometry, physical exam and medical history were documented. Logistic regression was performed. RESULTS We enrolled 376 children with mean age (sd) 8.05 years (3.03), a median (IQR) duration of ART of 5.9 years (3.2-8.4). Majority of the children (64%) had been exposed to non nucleoside reverse transcriptase inhibitors (NNRTIs). A third were severely immunosuppressed (CD4% ≤15%) at ART initiation. At the time of the study, the majority (89%) were virologically suppressed (VL <1000 copies/ml). Prevalence of 25(OH)D <30 ng/ml was 49 (13%) of 375 participants and 11 (3%) had 25(OH)D <20 ng/ml. Lopinavir/ritonavir regimen was independently associated with 25(OH)D <30 ng/ml; OR 0.27 CI (0.13-0.57), p value-0.002. Serum 25(OH)D <20 ng/ml was associated with CD4 count ≤15% at ART initiation OR 6.55(1.30-32.9), p value-0.023 and use of NNRTIs; OR 10.9(1.22-96.2), p value-0.03. CONCLUSION We found a low prevalence of suboptimal vitamin D compared to earlier reports. Severe immunosuppression at ART initiation and use of NNRTIs increases odds of deficiency. Vitamin D supplementation should be considered in severely immunosuppressed children initiating ART.
2.
Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3.
Lathers, DM, Clark, JI, Achille, NJ, Young, MR
Cancer immunology, immunotherapy : CII. 2004;(5):422-30
Abstract
Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects. These defects are associated with a poor prognosis and are mediated, in part, by immune inhibitory CD34(+) progenitor cells, whose numbers are increased in the peripheral blood of HNSCC patients. Immune inhibitory CD34(+) cells are also present within HNSCC tumors. A phase IB clinical trial was conducted with HNSCC patients to determine if treatment with the differentiation-inducer 25-hydroxyvitamin D(3) could diminish CD34(+) cell levels and improve a panel of immune parameters. Here we present the results of treatment with orally administered escalating doses (20, 40, 60 microg) of 25-hydroxyvitamin D(3), with an emphasis on the six patients who received the maximum dosage of 60 microg per day. Peripheral blood was collected at 0, 1, 2, 4, and 6 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of this pilot study demonstrated that treatment of HNSCC patients with 25-hydroxyvitamin D(3 )reduces the number of immune suppressive CD34(+) cells, increases HLA-DR expression, increases plasma IL-12 and IFN-gamma levels, and improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D(3) treatment did not modulate plasma IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-beta levels.
3.
Phase IB study of 25-hydroxyvitamin D(3) treatment to diminish suppressor cells in head and neck cancer patients.
Lathers, DM, Clark, JI, Achille, NJ, Young, MR
Human immunology. 2001;(11):1282-93
Abstract
Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects. These defects are associated with a poor prognosis and are mediated, in part, by an increased number of immune inhibitory CD34(+) progenitor cells in their peripheral blood and tumor. The CD34(+) cells suppress autologous T-cell functions. Our prior work had shown that the differentiation inducer 1alpha,25-dihydroxyvitamin D(3) could drive the differentiation of CD34(+) cells isolated from HNSCC patients into dendritic cells. A phase IB clinical trial was initiated with HNSCC patients to determine if 25-hydroxyvitamin D(3) treatment could diminish CD34(+) cell levels and improve immune function. Six patients per treatment group were orally administered 20 or 40 microg/day 25-hydroxyvitamin D(3) for six weeks. Peripheral blood was collected at 0, 1, 2, 4, 6, and 8 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of these pilot studies showed that 25-hydroxyvitamin D(3) reduced the presence of immune suppressive CD34(+) cells and improved immune competence of HNSCC patients.