The renal-bone axis in older people living with HIV on stable antiretroviral therapy: A sub-analysis of the GS-US-104-0423 study.

BACKGROUND: Data on low bone mineral density (BMD) in people living with HIV (PLWH) are mainly derived from younger adults; little is known about how antiretroviral therapy (ART) and alterations in the renal-bone axis relate to BMD in older PLWH. METHODS: Cross-sectional study of men > 50 years and post-menopausal women with HIV. Antiretroviral therapy exposure was stratified into four groups based on use of tenofovir disoproxil fumarate (TDF) and protease inhibitors (PI): non-TDF/non-PI, non-TDF/PI, TDF/non-PI, and TDF/PI. Bone mineral density was measured by dual X-ray absorptiometry (DXA). Bone turnover/regulatory markers and renal tubular function were analysed in stored plasma and urine samples. The association of ART exposure and bone/renal biomarkers on BMD was explored using logistic regression models. RESULTS: 247 individuals (median [IQR] age 57 [53, 65] years; 47% female; 13% of Black ethnicity; CD4 count 643 [473, 811] cells/mm3; and 98% with HIV RNA < 200 copies/mL) were included. Bone turnover and renal tubular function differed significantly by ART exposure. In analyses adjusted for demographic and traditional renal/bone risk factors, exposure to TDF and PI was associated with a fourfold greater risk of low BMD at the femoral neck and exposure to TDF and/or PI with a threefold greater risk of low BMD at the lumbar spine. The relationship between ART and low BMD was not altered by further adjustment for bone turnover or renal tubular function markers. CONCLUSIONS: The associations between low BMD and ART exposure (TDF vs. non-TDF and boosted vs. unboosted third agents) were minimally affected by adjustments for bone and kidney biomarkers.

Fractures and the gut microbiome.

PURPOSE OF REVIEW: The role of the gut microbiome in the pathogenesis of several inflammatory, non-AIDS comorbidities, such as cardiovascular disease, cognitive impairment and liver disease has become a focus of recent research. Low bone mineral density (BMD) and increased fracture incidence in people living with HIV (PLWH) is also widely reported, however, the relationship between alterations in the gut microbiome and bone disease in PLWH has not been previously reviewed. RECENT FINDINGS: Murine models that manipulate the gut microbiome, either through breeding of 'germ-free' mice or antibiotic-depleted gut microbiome, show differences in bone mineral density and bone mass in those with altered gut microbiome. This effect is reported to be driven via changes in the gut-immune-skeletal axis, with changes favouring bone resorption. Several inflammatory conditions wherever bone loss is a prominent feature, such as rheumatoid arthritis and inflammatory bowel disease, have also reported alterations in the gut microbiome, which are associated with bone loss, again through changes in the gut-immune-skeletal axis. SUMMARY: The interplay between the gut microbiome and the immune-skeletal axis in HIV represents a complex relationship. Alterations in the gut microbiome, which induce an activated immune phenotype and inflammatory milieu are associated with non-AIDS comorbidities in PLWH and bone loss in several other conditions characterized by chronic immune activation and inflammation. It is, therefore, likely that there are comparable effects between altered gut microbiome and bone loss in HIV, however, further research is required to better define this relationship in populations of PLWH.