Decreased bone turnover in HIV-infected children on antiretroviral therapy

Abstract

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 xray 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.

Cytokines in HIV infection: different methods of assessment require different interpretations

“…They associated the finding with the fact that children from their cohort had a well controlled viral replication and long-term antiretroviral therapy [1]. Similar results were observed by the same group in a prior crosssectional study [2].…”

“…Those seemingly opposite results may be because of the conditions under which cytokines were measured: whereas Shen et al [1] and Shiau et al [2] assessed plasma cytokines ex vivo, we measured the same cytokines after in-vitro stimulation of peripheral blood cells with phytohemagglutinin (PHA) [3].…”

“…We are grateful for the interests shown by Munhoz and Moraes-Pinto [1] regarding our article entitled 'Persistently lower bone mass and bone turnover among South African children living with well controlled HIV' [2].…”

Older age at Initiation of Antiretroviral Therapy Predicts Low Bone Mineral Density in Children with perinatally-infected HIV in Zimbabwe

“…Other strengths of this study are the prospective and (based on symptoms) unselected recruitment of participants. Until now, DXA-based studies in CWH in Sub-Saharan Africa have been limited to South Africa 43 . DXA capacity is severely limited across the region 44 so that such studies are logistically challenging.…”

Impact of HIV-1 Infection and Antiretroviral Therapy on Bone Homeostasis and Mineral Density in Vertically Infected Patients

“…Studies analyzing the association between biochemical markers and ART are scarce, especially those conducted on vertically infected pediatric patients [19, 22, 23].…”