Decreased bone turnover in HIV-infected children on antiretroviral therapy

SUMMARY: In this study, we evaluated the relationships between immune activation, bone turnover, and bone mass in virally suppressed HIV-infected children and HIV-uninfected children in South Africa. We found that decreased bone mass may occur or persist independent of immune activation and altered bone turnover. PURPOSE: HIV-infected children and adolescents have deficits in skeletal growth which include decreases in bone mass and alterations in bone microarchitecture. However, the mechanism by which HIV infection compromises bone accrual in children and adolescents is unclear. The goal of this study was to evaluate the relationships between immune activation, bone turnover, and bone mass in a group of pre-pubertal HIV-infected children randomized to remain on ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) or switch to efavirenz-based ART in South Africa virally suppressed at the time of this study. METHODS: This cross-sectional analysis included 219 HIV-infected and 180 HIV-uninfected children enrolled in the CHANGES Bone Study conducted in Johannesburg, South Africa. Whole body (WB) bone mineral content (BMC) was assessed by dual x-ray absorptiometry and WB BMC Z-scores adjusted for sex, age, and height were generated. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx) and procollagen type I N-terminal propeptide (P1NP), were analyzed. Markers of immune activation were also measured, including cytokines IL-6 and TNF-alpha, as well as soluble CD14 and high-sensitivity C-reactive protein (CRP). RESULTS: Compared to uninfected controls, HIV-infected children had lower WB BMC Z-scores, similar IL-6 and TNF-alpha, higher soluble CD14 and high-sensitivity CRP, and lower markers of bone resorption (CTX) and bone formation (P1NP). Bone turnover markers were not different in those remaining on LPV/r or switched to efavirenz. CONCLUSIONS: Our findings suggest that in HIV-infected children with viral suppression, decreased bone accrual may occur or persist independent of immune activation and altered bone turnover.