Background and aims: Although HIV positive patients live longer with effective antiretroviral therapy (ART) they experience higher rates of both osteoporosis and fractures, with potential for significant morbidity as the population ages. A significant loss of bone mineral density (BMD) accompanies ART initiation, characterised by increases in bone turnover. Bisphosphonates decrease bone turnover and can limit loss of BMD. We aim to determine if the bisphosphonate alendronate can mitigate the BMS loss observed with ART initiation.
Methods: We will conduct a multi-centre, randomized, double-blind, placebo-controlled trial to determine the effect of weekly oral alendronate 70 mg versus placebo in preventing BMD loss with ART initiation. Eighty antiretroviral-naïve, HIV1 positive subjects will be randomised 1:1 to alendronate or placebo administered 2 weeks prior to and 12 weeks post ART initiation. Fasting bloods and BMD, determined by DXA, will be assessed prior to and at weeks 12, 24 and 48 after ART initiation, with regular assessments of safety.
Primary endpoint will be between-group difference in percentage change in hip BMD from baseline to week 48 of ART by intention to treat analysis. Secondary endpoints will include changes in spine BMD, body composition and bone turnover. We will store PBMC, serum and plasma to enable detailed studies of how changes in T cell and B-cell subsets with ART relate to changes in BMD and bone turnover. The sample size provides 80% power to determine a between-group difference of 2.3% in BMD of at week 48.
Expected outcomes: This project answers an important, clinically-relevant question that may result in a simple, therapeutic strategy to maintain bone health for the thousands of people living with HIV in Ireland that is directly clinically applicable. It will also extend the research capabilities of both the researchers and institutions in the conduct of multi-centre, investigator-initiated clinical trials.
