cholecalciferol and efavirenz

HIV infection and antiretroviral therapy (ART) may create unique risk factors for vitamin D insufficiency, including alterations of vitamin D metabolism by ART. We prospectively compared demographic and clinical parameters between vitamin D sufficient and insufficient HIV-infected (HIV+) adults, and assessed changes in these parameters among insufficient participants following standardized vitamin D supplementation.. HIV+ adults (≥ 18 years old) with HIV-1 RNA <50 copies/mL on ART were enrolled. Vitamin D sufficiency and insufficiency were defined as 25-hydroxyvitamin D (25(OH)D) ≥ 30 or <30 ng/mL, respectively. Insufficient participants received open-label vitamin D3 50,000 IU twice weekly for 5 weeks, then 8000 IU twice weekly to complete 24 weeks. The primary endpoint was success or failure to achieve 25(OH)D ≥ 30 ng/mL at week 24.. Ninety-seven participants enrolled (34 vitamin D sufficient, 63 insufficient); 32% female, 47% non-White, median age 46 years, ART duration 5 years, CD4+ T lymphocyte count (CD4) 673 cells/mm(3). 25(OH)D repletion was 83% (95% CI 71%-90%) successful. 25(OH)D levels correlated with both CD4 (r = 0.44, p = 0.01) and time on protease inhibitor (r = -0.35, p = 0.01). After adjusting for age, sex, race, nadir CD4 and baseline 25(OH)D: 1) current use of efavirenz exposure was associated with a 21.1 ng/mL higher week 24 25(OH)D level (p = 0.007), 2) per year use of zidovudine was associated with 7.1 ng/mL reduction in week 24 serum 25(OH)D (p = 0.05) and 3) every 1 ng/mL 25(OH)D increase was associated with a 3.3 cell/mm(3) CD4 increase (p = 0.06).. Vitamin D3 supplementation was effective in repleting 25(OH)D levels after 24 weeks. Current efavirenz use was positively associated with post-repletion 25(OH)D levels, while greater time on zidovudine was associated with lower post-repletion 25(OH)D levels. The association between improved CD4 recovery and vitamin D repletion suggests a potential benefit of vitamin D supplementation on immunologic recovery during HIV treatment.. This trial is registered at The Brazilian Clinical Trials Registry (U1111-1165-2537).

Topics: Adult; Alkynes; Antiretroviral Therapy, Highly Active; Benzoxazines; Brazil; Cholecalciferol; Cyclopropanes; Dietary Supplements; Female; HIV Infections; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Socioeconomic Factors; Vitamin D Deficiency

Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catabolic reactions (CYP24A1). The cells produced both 25-hydroxyvitamin D

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adolescent; Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Calcifediol; Calcitriol; Cells, Cultured; Cholecalciferol; Cholestanetriol 26-Monooxygenase; Cyclopropanes; Cytochrome P450 Family 2; Dermis; Female; Gene Expression Regulation, Enzymologic; Humans; Male; Reproducibility of Results; Ritonavir; RNA, Messenger; Stavudine; Vitamin D3 24-Hydroxylase; Young Adult

Tenofovir-containing antiviral therapy might result in acute renal failure and is able to induce tubular dysfunction with hypocalcemia. On the other hand, hypercalcemia induced by intoxication with colecalciferol has been described to induce renal failure in HIV-positive individuals as well. Here, the authors describe the unusual case of reversible renal failure due to hypercalcemia in a patient with low-dose colecalciferol substitution treated with tenofovir.. A 31-year-old HIV-positive female, CDC stage C3, was admitted to the authors' hospital with progressive renal failure and hypercalcemia. Antiretroviral therapy consisted of tenofovir and emtricitabine in combination with efavirenz. Additionally, she was on low-dose vitamin D(3) substitution (25 microg/d) and calcium supplementation (500 mg/d) due to systemic steroid treatment.. Additionally to regular control of renal function, serologic level of calcium should be supervised in patients concomitantly treated with tenofovir and colecalciferol.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Adenine; Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Calcium; Cholecalciferol; Cyclopropanes; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Emtricitabine; Female; Humans; Hypercalcemia; Immune Reconstitution Inflammatory Syndrome; Kidney Function Tests; Mycobacterium avium-intracellulare Infection; Organophosphonates; Osteoporosis; Tenofovir