Persistently lower bone mass and bone turnover among South African children living with well controlled HIV

Abstract

Objective: We evaluated longitudinal trends and associations between bone mass, bone turnover and inflammatory markers among South African children living with HIV (CLHIV) and controls.Design: We previously reported decreased bone mass among CLHIV independent of marked inflammation and increased bone turnover. The goal of this study was to evaluate longitudinal changes in bone mass, bone turnover and inflammation over 2 years.Methods: Longitudinal analyses were conducted among 220 CLHIV and 220 controls. Anthropometric measurements, physical activity, antiretroviral regimen, virologic and immunologic status, whole body (WB) and lumbar spine (LS) bone mineral content (BMC) and bone mineral density (BMD) were collected (enrollment, 12 and 24 months). Bone turnover markers including C-telopeptide of type I collagen (CTx) and procollagen type I N-terminal propeptide (P1NP) and inflammatory markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble CD14 and high-sensitivity Creactive protein (hsCRP) were collected at enrollment and 24 months.Results: Compared with controls, CLHIV had significantly lower mean WB-BMC, WB-BMD, WB-BMC z scores, LS-BMC and LS-BMD as well as lower bone formation (P1NP) and resorption (CTx), and higher hsCRP and soluble CD14 over 24 months. CLHIV on efavirenz (EFV) had consistently lower TNF-alpha and IL-6 compared with those on ritonavir-boosted lopinavir (LPV/r) at all time points. Conclusion:Over 2 years of follow-up, South African CLHIV had persistently lower bone mass, bone turnover, and macrophage activation. Lower bone mass and higher pro-inflammatory cytokine profiles were consistently observed among those on LPV/ r-based compared with EFV-based regimens.

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

“…By contrast, our study that was cited by Shen et al [1] showed that adolescents with detectable viral load had significantly lower IL-6 levels than controls, and those with an undetectable viral load had IL-6 levels comparable with controls [3].…”

“…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].…”

“…Munhoz and Moraes-Pinto [1] proposed an explanation of the discordant results between studies by Munhoz et al [3] and ourselves [2] with respect to measures of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) among adolescents and children living with HIV and HIV-uninfected controls. Munhoz et al [3] using in-vitro stimulation of peripheral blood cells with phytohemagglutinin (PHA) reported that adolescents with detectable viral load had significantly lower IL-6 and comparable TNF-alpha levels than controls, and those with an undetectable viral load had IL-6 and TNF-alpha levels comparable with controls.…”

“…Shen et al [1] did not detect elevated pro-inflammatory markers in children living with HIV over the 2year study period compared with controls. 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].…”

Cytokines in HIV infection: authors’ reply

“…Munhoz and Moraes-Pinto [1] proposed an explanation of the discordant results between studies by Munhoz et al [3] and ourselves [2] with respect to measures of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) among adolescents and children living with HIV and HIV-uninfected controls. Munhoz et al [3] using in-vitro stimulation of peripheral blood cells with phytohemagglutinin (PHA) reported that adolescents with detectable viral load had significantly lower IL-6 and comparable TNF-alpha levels than controls, and those with an undetectable viral load had IL-6 and TNF-alpha levels comparable with controls.…”