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Vitamin D Deficiency in EuroSIDA Linked to All-Cause Mortality and AIDS
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Analyzing almost 2000 cohort members, EuroSIDA investigators found a higher risk of a new AIDS diagnosis or death from any cause in people with lower vitamin D levels [1]. These associations held in analyses corrected for an array prognostic factors in people with HIV.
EuroSIDA researchers randomly selected 2000 cohort members older than 16 who had at least 1 month of follow-up and CD4 and viral load measurements within 6 months. A single laboratory measured 25OHD levels in 1985 samples, and the investigators divided them by level into lower, middle, and upper thirds (tertiles). The low tertile (25OHD below 12 ng/mL) included 714 people, the middle tertile (12.1 to 20 ng/mL) included 622, and the high tertile (above 20 ng/mL) included 649.
Median age was similar across tertiles (39.3 T1, 38.1 T2, and 38.0 T3, P = 0.19), as were CD4 count (356 T1, 376 T2, and 360 T3, P = 0.13) and viral load (2.5 log T1, 2.6 log T2, and 2.6 log T3, P = 0.36). Median month of sample collection was February 2002 in T1, November 2001 in T2, and September 1999 in T3 (P < 0.0001). The low tertile had a significantly lower proportion of whites (81.9% T1, 87.8% T2, and 90.6% T3, P < 0.001) and a significantly lower proportion of people infected during sex between men (35.3% T1, 44.4% T2, and 45.9% T3, P = 0.0022).
Multivariate analysis identified several factors independently associated with 25OHD levels in the low tertile, including nonwhite race (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.19 to 2.15, P = 0.0017), each additional 10 years of age (OR 1.12, 95% CI 1.01 to 1.24, P = 0.035), sample collection during spring (when vitamin D levels would be low after scanty winter sun exposure), and living in central or northern Europe rather than sunnier southern Europe. Compared with cohort members infected during sex between men, those infected during heterosexual sex had a 51% higher risk of being in the lowest tertile (OR 1.51, 95% CI 1.18 to 1.92, P = 0.001) and those infected by injecting drugs had a 65% higher risk (OR 1.65, 95% CI 1.26 to 2.15, P = 0.0003).
A multivariate model devised to predict the impact on low D levels on risk of progression to AIDS, non-AIDS disease, or death considered gender, ethnic origin, HIV risk group, region of Europe, HBV and HCV status, prior AIDS, antiretroviral exposure, age, CD4 count, nadir CD4 count, viral load, date of vitamin D sampling, season of sampling, and date of joining EuroSIDA. Compared with people in the low tertile, people in the middle and high tertile had an independently lower risk of death from any cause or new AIDS (but not new non-AIDS diseases) at the following incidence rate ratio (IRR):
New AIDS diagnosis
-- Middle tertile: IRR 0.58, P = 0.0086
-- High tertile: IRR 0.61, P = 0.020
Death from any cause
-- Middle tertile: IRR 0.68, P = 0045
-- High tertile: IRR 0.56, P = 0.0039
During follow-up, 48 people died from an AIDS-related cause and 112 died from non-AIDS causes. Repeating the multivariate analysis according to cause of death, the researchers found that people in the highest tertile had a 40% lower risk of a non-AIDS death than people in the lowest tertile (IRR 0.60, 95% CI 0.37 to 0.098, P = 0.043). But being in the high tertile had no significant impact on AIDS death. In this analysis, being in the middle tertile did not significantly affect the risk of AIDS death or non-AIDS death.
The EuroSIDA investigators noted that their analysis is limited by its observational nature and single vitamin D measurement, but a longitudinal study is under way. They called for "intervention studies on correction of vitamin D deficiency . . . to gain a better understanding of the pathophysioloigcal mechanisms behind these findings."
Reference
1. Viard JP, Souberbielle JC, Kirk O, et al. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O413.
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