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Title: Bone mineral status and renal tubular dysfunction in HIV-positive men
Author: Samarawickrama, Amanda
ISNI:       0000 0004 7427 117X
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2018
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Background: As HIV-positive patients live longer, they are experiencing age-related comorbidities, including bone and renal disease. The aetiology is multifactorial, comprising traditional and HIV-related factors, including antiretroviral therapy (ART). However, whether reduced bone mineral density (BMD) translates into a higher fracture risk remains unclear. Aims: My main aim in my thesis was to conduct a cross-sectional study with changes over time to investigate BMD and renal tubular dysfunction (RTD) in a relatively homogenous group of white, ART-experienced HIV-positive men in the UK, who were mostly men who have sex with men (MSM) and mainly on tenofovir disoproxil fumarate (TDF). The aims I investigated were: 1. The prevalence and risk factors associated with reduced BMD at baseline and the change in BMD over 12 months and the factors associated with loss of BMD. 2. The utility of the FRAX® score and peripheral dual-energy x-ray absorptiometry (pDXA) as screening tools. 3. The utility of albumin/protein ratio (APR) in differentiating RTD from other proteinuria and the relationship between RTD and bone. Methods: I designed a prospective cohort study of HIV-positive men attending an HIV outpatient clinic. Participants underwent central DXA (cDXA) and pDXA, fasting blood and urine tests (including bone turnover markers [BTMs] and retinol binding protein creatinine ratio [RBPCR]) and completed a questionnaire at baseline and at 12 months. Results: I found a low prevalence of reduced BMD. Mainly ‘traditional’ risk factors were associated with reduced BMD. The change seen in absolute BMD at 12 months was small, reflecting the short follow-up period. The only factor associated with a greater than smallest detectable difference (SDD) reduction in BMD was a detectable HIV viral load. FRAX® was not sensitive enough as a screening tool, and pDXA was slightly more sensitive, although combining FRAX® and pDXA was not much better than FRAX® alone. RTD prevalence was too low to conduct meaningful analyses. Overall, 20.7% had RBPCR-defined RTD and there was a borderline association between severe RTD and BMD at the lumbar spine, but not with BTMs. Conclusions: In my cohort of mainly white, ART-experienced (mainly exposed to TDF) HIVpositive MSM in the UK, the prevalences of reduced BMD and RTD were low. The factors associated with reduced BMD were mainly ‘traditional’ factors and probably reflects a ‘return to health’ with ART in these men. There was not much change in BMD over 12 months, which is probably reflective of the short follow-up period. Using FRAX® and pDXA may be useful as screening tools, but further work is needed before any firm conclusions can be made in this cohort. Although one-fifth had RBPCR-defined RTD, the clinical significance of these findings and the impact on bone health is yet to be fully elucidated.
Supervisor: Davies, Kevin A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available