Background
The risk of osteonecrosis (ON), or bone death due to inadequate vascular supply, is estimated to be 3-100 fold higher in people with HIV (PWH) compared to the general population. However, most information on ON in PWH is from older case reports or small case control studies and cohort studies limited by small numbers of ON cases. This leaves critical gaps in our understanding of ON risks in the current HIV treatment era as the population of PWH continue to age.
Methods
We examined ON among PWH in routine clinical care at 8 sites in the CNICS cohort from ~2012-2023 (dates vary slightly by site). ON cases were identified using diagnoses codes; with one site validating diagnoses through clinical documentation and radiology reports. We used adjusted Cox proportional-hazards models to estimate the association between demographic and clinical characteristics and time to ON, with censoring at the time of event, loss to follow up, death, or study end. Covariates included age, race/ethnicity, sex, CD4 count, viral load, history of AIDS-defining illnesses (ADIs), corticosteroid use, co-infection with hepatitis C virus, liver function (FIB-4), kidney function (eGFR), hypertension, dyslipidemia, diabetes, and use of marijuana, tobacco, and alcohol. CD4 count and viral load were time-updated, while other factors were measured at study baseline. We analyzed Pneumocystis jirovecii pneumonia (PJP) separately from other ADIs due to steroid treatment considerations.
Results
Among 18,658 PWH, the mean baseline age was 44 years, 37% were Black, 15% Hispanic/Latine, and 17% were female. During follow up, 276 PWH (1.5%) developed ON. In adjusted analyses, factors associated with increased ON risk included older age (hazard ratio HR 1.21 (1.05-1.39 per 10 years), lower CD4 cell count (0.95: 0.91-0.99 per 100 cells/mm3), ADI without PJP (1.66: 1.28-2.16), PJP (2.03: 1.50-2.76), steroid use (1.73: 1.35-2.22), tobacco use (1.52: 1.18-1.95), and alcohol use (1.40: 1.12-1.76) (see table).
Conclusions
In the current treatment era, HIV-related factors such as lower CD4 cell count and ADIs continue to be significant predictors of ON risk among PWH as well as known risk factors in the general populations such as age and corticosteroid use. Behavioral factors, including tobacco and alcohol use, highlight actionable prevention targets reinforcing the importance of early antiretroviral therapy initiation and lifestyle interventions.