SUMMARY: Vitamin D supplements lowered levels of parathyroid hormone, which promotes bone breakdown, in HIV positive young adults using tenofovir, according to a report at CROI 2011.

By Liz Highleyman

Peter Havens (Photo: Liz Highleyman)

Vitamin D is necessary for maintaining healthy bones. People with vitamin D deficiency typically have elevated levels of parathyroid hormone (PTH), which breaks down bone to release calcium into the bloodstream and reduces absorption of phosphate by the kidney tubules.

High PTH levels are also seen in people taking tenofovir (Viread, also in the Truvada and Atripla combination pills), which has been linked to loss of bone mineral density and impaired kidney function.

In a presentation at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston, Peter Havens from the Medical College of Wisconsin described a study looking at the effects of vitamin D supplementation on PTH levels and other bone biomarkers among participants in Adolescent Trials Network Study 063.

Noting that vitamin D3 treatment increases kidney phosphate absorption in people with vitamin D deficiency, the investigators hypothesized that vitamin D administration might also increase phosphate absorption and decrease serum levels of PTH, bone alkaline phosphatase, and CTx (a byproduct of collagen breakdown) in HIV positive adolescents and young adults taking tenofovir.

This randomized controlled trial included 203 participants age 18-24 years (mean 21 years). About 30% were women and half were African-American. Overall, they had well-controlled HIV disease; all were on antiretroviral therapy (ART), viral load was below 5000 copies/mL, and the mean CD4 cell count was 587 cells/mm3.

Participants were assigned to receive 50,000 IU vitamin D or placebo every 4 weeks for 12 weeks, taken as 3 directly observed oral doses to ensure adherence. They were stratified according to whether their ART regimens did (n = 118) or did not (n = 85) include tenofovir. As a group, tenofovir recipients had a shorter duration of HIV infection, lower viral load, and less advanced HIV disease.

Results

	More than 80% had vitamin D insufficiency or deficiency at study entry.
	At baseline, participants taking tenofovir had significantly lower kidney tubule phosphate absorption than those not taking the drug.
	Tenofovir recipients had significantly higher baseline PTH levels than non-recipients:
	Overall: 48 vs 31 pg/mL; Vitamin D deficient: 52 vs 35 pg/mL; Vitamin D sufficient: 43 vs 27 pg/mL.
	Baseline CTx and bone alkaline phosphatase levels were similar in the tenofovir and non-tenofovir groups.
	After 12 weeks, 95% of participants in the vitamin D supplement arm reached adequate levels of vitamin D (up from 47% at baseline), with no significant change in the placebo arm.
	Kidney tubule phosphate absorption did not change in either the vitamin D or placebo groups.
	PTH levels decreased significantly among tenofovir recipients taking vitamin D supplements (from 49 to 42 pg/mL), but did not change in the non-tenofovir group regardless of supplementation.
	While PTH levels decreased in the tenofovir vitamin D group, they did not fall to levels seen in participants not taking tenofovir.
	CTx levels did not change significantly with vitamin D supplementation in either group, but bone alkaline phosphatase decreased slightly in the tenofovir group.
	No clinical bone or kidney problems were observed in either group.

"Supplementation with vitamin D3 50,000 IU monthly for 12 weeks in HIV+ youth was safe and reduced vitamin D insufficiency by 46%," the investigators concluded.

"Vitamin D was associated with a significant decrease in PTH in those on [tenofovir]-containing combination ART," they continued. "The effect of vitamin D on PTH was seen only in those on [tenofovir], suggesting a possible interaction between [tenofovir], PTH, and vitamin D.

"In a lot of ways tenofovir use looks like vitamin D deficiency," Havens elaborated at a CROI press conference. Among people on tenofovir, even if they have normal vitamin D, "PTH will be high, suggesting the body is not happy about calcium...if [you are] on tenof, [your] bones may be not so happy."

However, he said, it is "way too early" to say whether monitoring PTH levels might be beneficial. Bone mineral density was not measured, and longer studies are needed to show whether decreased PTH ameliorates bone loss among tenofovir recipients. Follow-up studies are in progress to test varying doses of vitamin D and the addition of calcium supplements.

Investigator affiliations: Medical College of Wisconsin, Milwaukee, WI; National Inst of Child Health and Human Development, NIH, Bethesda, MD; Western Human Nutrition Research Ctr, Univ of California, Davis, CA; Westat, Rockville, MD; Univ of South Florida, Tampa, FL; Univ of California, San Francisco, CA.

3/29/11

Reference
P Havens, R Hazra, C Stephensen, et al. Vitamin D3 Supplementation Decreases PTH in HIV-infected Youth Being Treated with TDF-containing Combination ART: A Randomized, Double-blind, Placebo-controlled Multicenter Trial: Adolescent Trials Network Study 063. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 80.