Tenofovir Disoproxil Fumarate Salvage Therapy in HIV-Infected Children and a Study of Its Effect on Bone Metabolism
Tenofovir disoproxil fumarate (TDF) was approved for the treatment of HIV-infected adults in
October 2001. In November 2001, we began enrollment to our phase I/II study of tenofovir DF
in HIV-infected children (02-C-0006). That study has completed enrollment. The virologic
and immunologic responses seen on that study in a group of heavily treatment-experienced
children with multidrug resistant HIV were surprisingly good. The drug was well tolerated,
but significant decreases in bone mineral density were seen in a minority of patients.
With the current study we will enroll and systematically investigate HIV-infected children
for whom tenofovir DF is being used as part of salvage combination HIV therapy. The primary
objective of the study is to characterize the change in bone mineral density (BMD), as
measured by lumbar spine dual-energy x-ray absorptiometry (DEXA), during and following
treatment with tenofovir DF-containing antiretroviral therapy in HIV-infected children. The
study will enroll 3 cohorts of children: 1) HIV-infected children about to start a tenofovir
DF-containing antiretroviral regimen, 2) HIV-infected children already on tenofovir DF with
available baseline DEXA results, and 3) HIV-infected children already on tenofovir DF but
without baseline DEXA results who will come here for investigations of bone metabolism.
Studies of bone metabolism will include periodic measurements of serum and urine calcium and
phosphorus, PTH and vitamin D levels, bone resorption markers (urinary collagen cross-linked
N-telopeptide and free deoxypyridinoline), bone formation markers (serum osteocalcin and
bone specific alkaline phosphatase), IGF-1 levels, bone age, and DEXA scans. Patients about
to start tenofovir DF (cohort 1) will be offered the option of having a transiliac crest
core bone biopsy with tetracycline labeling performed at baseline and at 6 months to assess
static and dynamic parameters of bone quality and turnover (histomorphometry). Subjects with
substantial presumed tenofovir DF-related bone toxicity who are deriving benefit from their
tenofovir DF-containing antiretroviral drug regimen will be offered the option of
pamidronate therapy. The effects of pamidronate treatment on bone toxicity associated with
tenofovir DF in these patients will be assessed in an exploratory fashion. It is expected
that up to 40 patients with baseline BMD measurements will be enrolled onto this protocol.
An additional 10 patients who are undergoing tenofovir DF treatment but who did not receive
baseline BMD measurements will also be permitted to enroll in order to contribute to the
data used to characterize changes in toxicity.
Interventional
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
United States: Federal Government
040234
NCT00088309
June 2004
May 2006
Name | Location |
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National Cancer Institute (NCI) | Bethesda, Maryland 20892 |