HIV, vitamin D status and bone health in South African women.

Lead Research Organisation: MRC Human Nutrition Research Group

Abstract

I will examine the effect of HIV and its treatment (ART) on bone health such as osteoporosis and vitamin D status in South African women. HIV-positive and HIV-negative (control) women will have baseline DXA scans to estimate bone mineral density (BMD) and a variety of blood and urine tests to assess bone turnover/vitamin D. These will be repeated at 1 year to see how much bone is lost and how vitamin D status changes over this time. All women will be assessed for physical activity and dietary intake because these are important factors in bone health.
The HIV-positive women will be divided into 2 groups; those receiving and those not receiving ART to examine the effect of ART on bone and vitamin D.
We anticipate HIV-infection and/or ART will have negative effects on bone density and vitamin D status. Low BMD is seen in osteoporosis and can result in bone fractures. Poor vitamin D status is associated with weak bones, reduced immunity and may increase the risk of cancer.

If we demonstrate that HIV-positive women are at risk of osteoporosis and low vitamin D we will be able to recommend further research to test treating these conditions.

Technical Summary

HIV and osteoporosis are global health priorities; there is emerging evidence that they may be inter-related. It is in Africa that the long-term skeletal sequelae of low BMD are likely to predominate and cause fragility fractures. All related research has been undertaken in Europe/ North America. My Fellowship aims to reposition the "HIV-vitamin D-bone health" agenda in an African context and focus on aspects so far neglected. The experience gained in Africa will have significance and application in the UK and is in line with the strategic aims of the MRC.
Anti-Retroviral Therapy (ART) is associated with bone loss, more recently it has been associated with poor vitamin D status. However the causative mechanisms remain unclear because of suboptimum study design employed in studies so far. Published work is often retrospective and lacks a HIV-negative control group.
The current evidence to support a link between HIV/vitamin D/bone health is lacking. I have conducted a critical appraisal of the literature and generated the following hypotheses as high priority for my future research:

1. HIV-infection is associated with lower BMD and higher bone turnover in HIV-positive South African women compared with age matched controls.
2. HIV-infection is associated with lower vitamin D status despite adequate opportunity for skin synthesis of vitamin D.
3. ART use accelerates bone loss in women with pre-existing HIV-infection.
4. ART initiation results in a decline in vitamin D status. Plasma 25(OH)D concentration (as a marker of vitamin D status) decreases over time after initiation of ART.

I have designed a study to test these hypotheses. The planned study will be carried out in Johannesburg and allow quantification of the magnitude of any effects and their potential clinical relevance. Study methods will include laboratory measurement of bone turnover, anthropometry, dietary and physical activity questionnaires and DXA measurement of BMD and body composition in HIV-positive women and HIV-negative controls.
This is a collaborative exercise that will provide a unique opportunity to undertake the first essential research of this kind in Africa and has the potential to provide results that could inform future research directions and policy initiatives. This Fellowship will provide a platform for my future career as a clinical academic and form the basis of a longer programme of work examining the relations between infection, bone health and poor vitamin D status.

Publications

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