NATAP: Vitamin D Supplementation/HIV/HAART/Bone Health/Fractures

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Subject: NATAP: Vitamin D Supplementation/HIV/HAART/Bone Health/FracturesNATAP http://natap.org/_______________________________________________Vitamin D Supplementation, HIV, HAART, Bone Health, FracturesThe authors of this published study this month in the journal AIDS question the taking of vitamin D supplementation for HIV+ individuals saying the "Limited data on vitamin D supplementation in HIV-positive patients have shown transient, beneficial effects on PTH, but no effects

on BMD.....Conclusion: The benefits of vitamin D supplementation in this population need to be demonstrated before widespread ‘test and treat’ policies can be recommended as part of routine clinical practice." In response to the attention reported online given by this publication I consulted & got responses from leading US-based bone & HIV/bone expert researchers/doctors, their comments are immediately below followed by the full text of the published article. Jules Levin"No-one thinks that vitamin D improves BMD by very much, even in HIV- populations, unless there is preexisting evidence of unmineralized bone due to vitamin D deficiency with secondary hyperparathyroidism or osteomalacia. The data on fractures are also mixed in HIV- populations. HOWEVER, everyone agrees that vitamin D deficiency (defined as <20 ng/ml by the IOM, < 30 by others) is a bad thing for many organ systems and it will take many years to get the data solely in HIV+ populations. In particular, randomized clinical trials with fracture as endpoints will require thousands of participants. Thus, in my opinion, it is entirely reasonable to extrapolate from HIV- to HIV+ populations and recommend screening for vitamin D deficiency and repletion to serum levels between 20 and 30 ng/ml. There is no reason to think that this will be a bad thing for HIV+ patients and it may be helpful.""The other approach would be not to test everyone, but to give everyone supplementation. How much is another question, but I generally give 1000-2000 IU/d. For those with other RFs, like EFV use, I recommend 2000 IU/d. I reserve testing for those with known low BMD, those with symptoms suggestive of osteomalacia, and those with a h/o falls, since at least in HIV-neg, these populations are most likely to benefit.""Vitamin D with calcium supplementation has only convincingly been able to reduce fractures in elders who are likely vitamin D deficient. The IOM recommends a serum 25(OH)D level of 20 and above, while most "bone heads" recommend a level of 30 and above in persons with medical conditions that put them at risk for poor bone health. Low vitamin D levels are a risk marker for poor health outcomes. The strategy of measurement and then supplementation is reasonable in patients who are under medical care for chronic conditions."-----------------------------AIDS:

28 January 2012 Editorial ReviewEffects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients - pdf attached

Childs, a; Welz, a; Samarawickrama, b; Post, A.a,caKing's College Hospital bBrighton and Sussex Medical School cKing's College London School of Medicine, London, UK.

Abstract

Objectives: In the era of combination antiretroviral therapy (cART), vitamin D deficiency, low bone mineral density (BMD) and

fractures have emerged as subjects of concern in HIV-positive patients.

Testing for vitamin D deficiency has been widely adopted in clinical practice even though the benefits of vitamin D supplementation in this population remain uncertain. The objective of this review was to evaluate the evidence for such a strategy.Design: Systematic review of the literature on vitamin

D deficiency in HIV infection, the effects of cART on vitamin D status,

and the effects of vitamin D deficiency and cART on parathyroid hormone

(PTH), bone turnover, BMD and the incidence of fractures in HIV-positive patients.Methods: PubMed was used to identify relevant articles up to September 2011.Results: Vitamin D deficiency, secondary hyperparathyroidism and low BMD are common in HIV-positive patients. Efavirenz is associated with a reduction in 25-hydroxy vitamin D levels,

tenofovir with secondary hyperparathyroidism, and cART with increased bone turnover and low BMD. The clinical significance of low BMD, however, remains unclear, especially in younger patients. Although the incidence of fractures may be increased in HIV-positive patients, the contribution of low BMD and vitamin D deficiency to these fractures is uncertain. Limited data on vitamin D supplementation in HIV-positive patients have shown transient, beneficial effects on PTH, but no effects

on BMD.Conclusion: The benefits of vitamin D supplementation in this population need to be demonstrated before widespread ‘test and treat’ policies can be recommended as part of routine clinical practice.IntroductionWith the decline of opportunistic infections [1],

comorbidities affecting the liver, kidney, bone, cardiovascular and central nervous system have become increasingly prevalent and emerged as

important causes of death in the era of combination antiretroviral therapy (cART) [2]. Low bone mineral density (BMD) and vitamin D deficiency are both common in HIV-positive patients [3–6] and may contribute to the observed increased incidence of fractures in this population [7,8].

Recent studies have shown that cART may have effects on vitamin D, parathyroid hormone (PTH), bone turnover, BMD and the risk of developing

fractures. Consequently, measurement of 25-hydroxy vitamin D [calcidiol, 25(OH)D] and vitamin D replacement in those with low levels has been widely adopted in HIV clinical practice. However, evidence for the clinical benefit or cost effectiveness of such a strategy is lacking. Here we review the recent literature on vitamin D deficiency, the effects of cART on vitamin D status, the effects of vitamin D deficiency and cART on PTH levels, bone turnover, BMD and fractures, and

on vitamin D supplementation in HIV-positive patients.We used the PubMed database to systematically search the

English language literature for relevant articles using the following terms: vitamin D, PTH and bone, each combined with HIV. Articles published up to 30 September 2011 were considered for inclusion in our review. We also reviewed conference abstracts from the 2011 International AIDS Society and Conference on Retroviruses and Opportunistic Infections meetings for novel, as yet unpublished, insights.Vitamin D deficiency in HIV-positive patientsVitamin D status should be assessed by measurement of 25(OH)D [9].

Low 25(OH)D levels identify patients with vitamin D insufficiency [(20–30 ng/ml (50–75 nmol/l)], deficiency [10–20 ng/ml (25–50 nmol/)] or

severe deficiency [<10 ng/ml (<25 nmol/l)] [10]. The prevalence of vitamin D deficiency in HIV-positive patients ranges from 29 to 73% [4–6]. However, HIV infection per se is not associated with vitamin D deficiency (Table 1) [5,6,11,12]. Only one small study suggested that 25(OH)D levels may be lower in HIV-positive patients [13]. Subsequent studies have shown either similar or higher 25(OH)D levels [11,14], or similar or lower rates of vitamin D deficiency [5,6,11,12]

in HIV-positive patients compared with either HIV-negative patients or general population controls. As for vitamin D deficiency in the general population [10,15],

cross-sectional studies of vitamin D status in HIV-positive patients have identified the following risk factors for low 25(OH)D levels: black

or Hispanic ethnicity [4,5,16–19], reduced ultraviolet exposure or measurements obtained in fall or winter season [4,5,16,18], increased BMI [5,16], hypertension and a low exercise level [5]. On the contrary, lower estimated glomerular filtration rate has been associated with reduced odds of low vitamin D status [5,17]. HIV-parameters associated with low 25(OH)D levels include intravenous drug use [16,18], longer time since HIV diagnosis [16], CD4 cell count less than 200 cells/μl [4,6], current use of cART [4,5], and an undetectable [6] or detectable [19]

HIV RNA level. Although the clinical implications of vitamin D deficiency in HIV-positive patients remain to be defined, higher incidence rates of AIDS and death have been observed in patients with 25(OH)D levels less than 12 ng/ml at baseline [18].Vitamin D deficiency and combination antiretroviral therapyThe potential effect of cART on vitamin D status has received considerable attention recently; the emerging view is that specific antiretrovirals may affect 25(OH)D levels (Table 2) [4,16–18,20–30]