Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.


BACKGROUND
This trial is registered at The Brazilian Clinical Trials Registry (U1111-1165-2537).
Instituto Nacional de Infectologia Evandro Chagas (INI), FIOCRUZ, Av Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. lara.coelho@ini.fiocruz.br.
Lara
L
Coelho
Instituto Nacional de Infectologia Evandro Chagas (INI), FIOCRUZ, Av Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. sandra.wagner@ini.fiocruz.br.
Sandra W
SW
Cardoso
Instituto Nacional de Infectologia Evandro Chagas (INI), FIOCRUZ, Av Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. paula.luz@ini.fiocruz.br.
Paula M
PM
Luz
University of California, Los Angeles, Los Angeles, CA, USA. rhoffman@mednet.ucla.edu.
Risa M
RM
Hoffman
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. laura.mendonca@uol.com.br.
Laura
L
Mendonça
Instituto Nacional de Infectologia Evandro Chagas (INI), FIOCRUZ, Av Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. valdilea.veloso@ini.fiocruz.br.
Valdilea G
VG
Veloso
University of California, Los Angeles, Los Angeles, CA, USA. jscurrier@mednet.ucla.edu.
Judith S
JS
Currier
Instituto Nacional de Infectologia Evandro Chagas (INI), FIOCRUZ, Av Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. gbeatriz@ini.fiocruz.br.
Beatriz
B
Grinsztejn
University of California, Los Angeles, Los Angeles, CA, USA. JLake@mednet.ucla.edu.
Jordan E
JE
Lake
D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D048588:Benzoxazines / Q000627:therapeutic use; D001938:Brazil; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000097:blood; D003521:Cyclopropanes; D019587:Dietary Supplements; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D012959:Socioeconomic Factors; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy / Q000209:etiology
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D002762:Cholecalciferol; C098320:efavirenz