Tracing the Effects of Antiretroviral Induced Bone loss in People Living with HIV

Antiretroviral therapy (ART) has significantly increased the lifespan of people living with HIV (PLWH), but as this population ages, they face an elevated risk of osteoporosis, particularly among women. Bone loss is a well-documented consequence of ART, with tenofovir disoproxil fumarate (TDF) being strongly associated with decreased bone mineral density (BMD). Tenofovir itself has poor oral bioavailability, necessitating the development of prodrugs, TDF and tenofovir alafenamide (TAF), with TDF exhibiting greater adverse effects on bone health. Notably, the mechanisms underlying TDF-associated bone loss are not exclusive to HIV infection, as evidence suggests these effects occur in noninfectious environments as well. This is particularly relevant given the expanding use of ART for HIV prevention through pre-exposure prophylaxis (PrEP). To investigate the direct impact of TDF on bone health, we utilized a noninfectious C57BL/6 female mouse model to assess BMD changes over time. Dual-energy X-ray absorptiometry (DXA) scans were conducted at multiple time points to evaluate the progression of bone loss. Understanding the drug-specific effects of TDF on bone metabolism will provide valuable insights into optimizing ART regimens and mitigating long-term skeletal complications in both HIV-infected and at-risk populations.