Impact of HIV and antiretroviral initiation on skeletal biology

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ABSTRACT Osteoporosis and fractures are known complications of HIV and antiretroviral therapy (ART) but the mechanisms of HIV and ART associated bone loss are still uncertain because tissue-level data are lacking. In the parent grant (R21TW012367), we are performing a comprehensive longitudinal study to compare the skeletal effects of the two ART regimens (TDF/lamivudine/efavirenz and lamivudine/dolutegravir). We will evaluate bone density and strength using dual energy Xray absorptiometry (DXA) and High Resolution peripheral Quantitative CT (HRpQCT) with finite element analysis (Aim 1), obtain paired iliac-crest bone biopsies to evaluate histomorphometry and tissue-level mechanical properties using nanoindentation/ramen spectroscopy (Aim 2), and perform bone cell transcriptomics to explore underpinning molecular pathways. As PWH age, renal impairment is likely to increase as well as frequency of fracture. An association between proteinuria and osteoporosis/fracture has been recognized in people with and without HIV, although the mechanistic underpinnings of urinary loss of protein and bone fragility has not been established. Specific antiretrovirals, such as TDF cause proximal tubular dysfunction resulting in proteinuria but the effect of other co-morbidities and traditional factors also contribute. This administrative supplement offers a unique opportunity to study the role of proteinuria in bone loss among PWH in Brazil. Building upon the multidisciplinary collaboration of HIV and bone researchers from the U.S. and the University of São Paulo established in the parent grant, this supplement will provide additional opportunities for research and capacity building for aging-related research focusing on the kidney-bone axis