Low Vitamin D Predicts Death in HIV-Positive

Daniel M. Keller, PhD

November 19, 2013

BRUSSELS — Among patients infected with HIV, current levels of 25-hydroxyvitamin D are associated with the risk for death but not for other adverse events, a new study suggests.

"Earlier levels of 25-hydroxyvitamin D failed to predict death, suggesting the association diminishes with time," Jean-Paul Viard, MD, PhD, from the Hôtel-Dieu, Université Paris Descartes in France reported here at the 14th European AIDS Conference.

The study included patients from a previous study of the EuroSIDA cohort, in which severe vitamin D deficiency at baseline was associated with the risk for progression to death in a 5-year follow-up period.

The aim of the current study was to further assess the short- and long-term prognostic value of vitamin D deficiency for AIDS-defining and non-AIDS-defining events and death and to study the association of vitamin D deficiency with inflammatory markers.

The work used a 1:1 case-control design nested within the EuroSIDA cohort for each of the outcomes of AIDS events (n = 50 pairs), non-AIDS events (n = 63 pairs), and death (n = 42 pairs). Control individuals were matched with cases on the basis of age, sex, region of residence, CD4 count, and HIV RNA level at baseline and on the dates of the final samples.

Vitamin D was lower in cases of death than in controls, but only for the latest sample. Dr. Jean-Paul Viard

Measurements of vitamin D and inflammatory markers were done on stored plasma from the time of study entry, at the time of an event, and at a midpoint of follow-up, if available. The time from the first to last samples averaged 44.6 months (interquartile range, 22.7 - 72.3 months).

Of 50 deaths, 88% were from chronic conditions and 12% were sudden events such as heart attack, stroke, suicide, lung embolism, gastric hemorrhage, or violent death.

Although the odds of death were not associated with the baseline vitamin D level, they "decreased significantly by 46% for a 2-fold higher level of 25-hydroxyvitamin D," Dr. Viard reported. There was no association of the baseline, latest measurement, or annual percentage change in the level of vitamin D on AIDS-related or non-AIDS-related events.

"Vitamin D was lower in cases of death than in controls, but only for the latest sample, while interleukin-6 [IL-6] was higher in cases than in controls for all items," Dr. Viard said.

"Similarly, CRP [C-reactive protein] was higher in cases than in controls at the latest sample for AIDS-events and death, and it was also higher at baseline for people who were going to die. CD14 levels were higher in cases and in controls for AIDS events and death."

The percent change in the level of inflammatory biomarkers and the CD4 cell count reflected the vitamin D status. If patients were severely vitamin D deficient (<10 ng/mL), high-sensitivity IL-6, and high-sensitivity CRP increased by 4.66% per year and by 8.35% per year after adjustment for several variables, including season, sex, age, and region of residency. There was no change in these markers if patients had normal or moderately deficient vitamin D levels.

Soluble CD14 increased regardless of vitamin D status. CD4 counts increased by 7.00% per year for people deficient in vitamin D and by 11.14% per year for people nondeficient in vitamin D (both P < .01), but not at all for patients who were severely deficient.

Asked for perspective on these findings, session cochair Andrea Antinori, MD, from the National Institute for Infectious Disease in Rome, Italy, who was not involved with the study, told Medscape Medical News that he found the results interesting because "probably we don't have much information about the role of vitamin D, and more interestingly, not only its role in bone mineral density and fracture in the long term but even in immune activation inflammatory pathways" that can increase other risks, for example, for cardiovascular disease.

His recommendation is "monitoring vitamin D in all types of patients before treatment in the first phase of induction by drugs for long-term treatment," with eventual supplementation for patients found to be vitamin D deficient.

This study was supported by grants from the European Commission and the Swiss National Science Foundation and unrestricted grants from BMS, Janssen R&D, Merck, Pfizer, and GSK. Dr. Viard reports no relevant financial relationships. Dr. Antinori reports financial ties to BMS, Gilead, ViiV; Abbvie, BMS, Gilead, and Janssen-Cilag.

14th European AIDS Conference: Abstract BPD1/2. Presented October 17, 2013.


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