Tenofovir disoproxil fumarate and bone mineral density: a 60-month longitudinal study in a cohort of HIV-infected youths
Pediatric Infectious Diseases Unit, Department of Pediatrics, L Sacco Hospital, University of Milan, Milan, Italy. Antiviral therapy
(Impact Factor: 3.02).
Decreased bone mineral density (BMD) has been associated with the use of tenofovir disoproxil fumarate (TDF) in HIV-infected adults. The data in HIV-infected children are conflicting. The aim of this study was to assess the safety of a TDF-containing antiretroviral (ARV) regimen on BMD in paediatric patients. We report the results of a longitudinal 60-month follow-up study.
A total of 21 vertically HIV-infected Caucasian youths (10 male and 11 female) on ARV treatment containing lamivudine, efavirenz and TDF were enrolled (age range 4.9-17.9 years at baseline). BMD was measured at the lumbar spine and in the whole skeleton by DXA. Bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker and urinary N-telopeptide of type-I collagen (NTx) was measured as a bone resorption index.
Baseline mean (±sd) BMD measurements of HIV-infected patients expressed as z-scores were -0.7 (±0.9) for lumbar spine and -0.13 (±1.0) for the whole skeleton. BMD measurements did not change significantly during the 60-month observation period. Both BAP and NTx concentrations were higher than a reference group of controls at baseline and remained unchanged throughout the study.
Our data indicate that a TDF-containing regimen does not decrease the BMD of HIV-infected youths.
Available from: PubMed Central
- "In 16 Italian children (6–18 years) receiving suppressive ART regimens, replacing stavudine and PI with tenofovir and efavirenz did not result in smaller 12-month BMC or BMD increases relative to HIV-uninfected peers . Another study of 21 Italian children receiving tenofovir/efavirenz/lamivudine documented no significant change in BMD Z-score from baseline through 60 months . The lack of a negative effect on BMD observed in these studies may be explained by the use of a lower dose of tenofovir, lack of concomitant PIs and ART switch (instead of ART initiation). "
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ABSTRACT: The long-term impact on bone health of lifelong HIV infection and prolonged ART in growing and developing children is not yet known. Measures of bone health in youth must be interpreted in the context of expected developmental and physiologic changes in bone mass, size, density and strength that occur from fetal through adult life. Low bone mineral density (BMD) appears to be common in perinatally HIV-infected youth, especially outside of high-income settings, but data are limited and interpretation complicated by the need for better pediatric norms. The potential negative effects of tenofovir on BMD and bone mass accrual are of particular concern as this drug may be used more widely in younger children. Emphasizing good nutrition, calcium and vitamin D sufficiency, weight-bearing exercise and avoidance of alcohol and smoking are effective and available approaches to maintain and improve bone health in all settings. More data are needed to inform therapies and monitoring for HIV-infected youth with proven bone fragility. While very limited data suggest lack of marked increase in fracture risk for youth with perinatal HIV infection, the looming concern for these children is that they may fail to attain their expected peak bone mass in early adulthood which could increase their risk for fractures and osteoporosis later in adulthood.
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ABSTRACT: This review details recent findings from cohort studies that inform the prevalence, incidence and effects of antiretroviral therapy (ART) and HIV infection on low bone mineral density (BMD), osteoporosis and fractures in different populations of HIV-infected individuals. Although ART has been spectacularly effective in prevention of disease progression and improvement in survival, the effects of ART on bone health require more research.
Both HIV infection and ART are associated with significant bone loss in HIV-infected individuals. The clinical consequence of low BMD, fragility fractures are more common in older HIV patients, but the significance of low BMD remains unclear in younger individuals. Vitamin D deficiency is common, but the prevalence is no different to the general population, and no effect on BMD has been noted in cross-sectional studies. Frailty occurs at a prevalence of about 10% and is related to impaired immunity.
This review examines the contributions from recent cohort studies to the understanding of the pathogenesis of bone loss in HIV, and the complex and poorly understood relationship between the effects of HIV and that of ART on bone loss.
Available from: Tammy Meyers
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ABSTRACT: WHO antiretroviral treatment guidelines for HIV-infected children have influenced the design of treatment programmes in resource-limited settings. This review analyses the latest WHO first- and second-line regimen recommendations.
The recommendation to use lopinavir/ritonavir-containing first-line regimens in young children with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure is based on good quality evidence. Recent research suggests that lopinavir/ritonavir-containing first-line regimens should be extended to all young children, irrespective of prior NNRTI exposure. Strategies for overcoming the adverse metabolic effects of rifampicin-containing anti-tuberculosis therapy on antiretroviral therapy regimens have been under-researched in HIV-infected children, creating uncertainty about global recommendations.
Preferred second-line recommendations are largely predictable. The exception is that NNRTI-containing second-line regimens are recommended for children previously exposed to NNRTIs and who subsequently did not respond to lopinavir/ritonavir-containing first-line therapy. In these patients, second-line regimens containing newer protease inhibitors (PIs) such as darunavir and tipranavir, or integrase inhibitors such as raltegravir, should be evaluated. Newer antiretroviral agents including second-generation NNRTIs and PIs, C-C chemokine receptor type 5 inhibitors, and integrase inhibitors may assist in further refinement of existing regimen options.
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