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IAS 2009: Vitamin D Deficiency is Common among HIV Positive People and Is Associated with NNRTI Use, Black Race, and Smoking

Two research teams presented study findings at the recent 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) in Cape Town, South Africa, showing that inadequate vitamin D levels are highly prevalent among people with HIV, and individuals taking efavirenz (Sustiva) are at particularly high risk

U.K. Study

Tanya Welz from King's College Hospital and colleagues evaluated serum 25(OH)D, or circulating vitamin D levels, in a cross-sectional study of 1077 HIV positive adults seen on an outpatient basis in London during 2008.

About 60% were men, the median age was 41 years, 61% were black, and about one-third were white. Participants had relatively well-controlled HIV disease with a media CD4 count of 456 cells/mm³, but the average CD4 nadir (lowest-ever level) was considerably lower.

About 12% had never taken antiretroviral drugs and 79% were on combination antiretroviral therapy (ART). Approximately half were taking a non-nucleoside reverse transcriptase inhibitor (NNRTI) and about one-quarter were taking a protease inhibitor (PI).

Risk factors for severe vitamin D deficiency, defined as < 10 mcg/L, and elevated alkaline phosphatase (a biomarker associated with bone disease) were assessed. Exposure to sunlight is required for the body to synthesize vitamin D, and about one-third of participants were tested during the fall or winter when sun exposure in the U.K. is reduced.

Results

• The median serum 25(OH)D level was 13.3 mcg/L, with a range of 8.2 to 20.8 mcg/L.
• A majority of participants had low vitamin levels:
  • 91% with < 30 mcg/L (suboptimal);
  • 74% with < 20 mcg/L (deficient);
  • 35% with < 10 mcg/L (severely deficient);
  • 6% with an undetectable level.
• In a multivariate analysis including only patients on ART, independent predictors of serious vitamin D deficiency were:
  • Black race (odds ratio [OR] 2.6; P < 0.001);
  • Testing duringthe fall/winter season (OR 2.1; P < 0.001);
  • Nadir CD4 count below 200 cells/mm³ (OR 1.4; P < 0.05);
  • Current use of efavirenz (OR 1.9; P < 0.001).
• Patient sex and current CD4 count were not significantly associated with vitamin D deficiency.
• At all vitamin D levels, patients receiving tenofovir (Viread, also in the Truvada and Atripla coformulations) or efavirenz had higher alkaline phosphataselevels than those taking other antiretroviral drugs (though this was no long significant for efavirenz after excluding people who took both drugs).

"Hypovitaminosis D is almost universal in this cohort," the investigators concluded. "[Efavirenz] use was associated with a lower 25(OH)D and [tenofovir] with higher alkaline phosphatse."

"Further studies are required to define the potential mechanisms and clinical implications of this interaction between ART, vitamin D, and bone," they added.

Discussing their findings, they suggested that efavirenz might alter vitamin D levels by interfering with the CYP24 enzyme in the liver, which plays a role in vitamin D metabolism.

King's College and King's College Hospital London, London, UK.

U.S. Study

In a related study, researchers in New York City evaluated the prevalence of and risk factors for vitamindeficiency among 62 HIV positive men receiving care through a private practice.

The median age of the participants was 48 years. Nearly half were Hispanic, about one-third were white, and 16% were black. More than 90% were receiving combination ART, with 31% taking NNRTIs and 60% taking PIs. Again, the men had well-controlled HIV disease, with a median CD4 count of about 540 cells/mm³ and most having HIV viral load < 200 copies/mL. 

Here, too, the investigators measured serum levels of 25(OH)D. Vitamin D insufficiency was defined as a level between 20 and 30 ng/dL (50-75 nmol/L), deficiency was defined as < 20 ng/dL (< 50 nmol/L), and severe deficiency was defined as < 10 ng/dL (< 25 nmol/L).

Results

• Most study participants were found to have low vitamin D levels:
  • 34% insufficient;
  • 42% deficient;
  • 11% severely deficient.
• The median vitamin D level was significantly lower among NNRTI recipients compared with PI recipients (42.4 vs 64.9 nmol/L; P = 0.0017).
• NNRTI recipients were also significantly more likely than PI recipients to have vitamin D deficiency (74% vs 30%; odds ratio 6.62; P = 0.0017).
• Smoking was a significant predictor of severe vitamin D deficiency.
• Race/ethnicity, history of wasting, current CD4 count, and nutritional parameters, however, were not associated with deficiency.

Based on these findings, the researchers concluded, "Vitamin D deficiency and insufficiency were highly prevalent among asymptomatic HIV-infected men receiving combination ART."

"[T]he association of NNRTI receipt with lower median serum 25-[OH] vitamin D and deficiency, are consistent with NNRTI effect on vitamin D metabolism," they stated. "[O]ur findings suggest that periodic screening of vitamin D, and supplementation as needed, should be considered in the routine care of HIV-infected men."

New York Hospital Queens, Infectious Disease Division, Department of Medicine, New York, NY; Weill Cornell Medical College, New York, NY.

9/01/09

References

T Welz, K Childs, F Ibrahim, and others. Efavirenz use is associated with severe Vitamin D deficiency in a large, ethnically diverse urban UK HIV cohort. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract TUPEB186.

Rubin and P Wasserman. Highly prevalent vitamin D deficiency and insufficiency among an urban cohort of human immunodeficiency virus (HIV)-infected men under care. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract CDB103.