Tenofovir

Studies have drawn mixed conclusions about the association of tenofovir treatment with bone loss. In one study the degree of bone loss reported after five years of tenofovir follow-up was marginal and likely to reflect ageing rather than the specific drug regimen.1 A 2002 clinical trial found no significant change in bone density after 48 weeks of treatment with tenofovir.2

However, at least two randomised clinical trials have found greater decreases in BMD in patients randomised to receive tenofovir/FTC (Truvada) than abacavir/3TC (Kivexa). The European ASSERT study found greater decreases in BMD after 48 weeks of first-line treatment with Truvada than with Kivexa – both in combination with efavirenz – both in the hip (-3.6 vs -1.7%) and in the lumbar spine (-2.4 vs -1.6%).3

Although the clinical significance of the ASSERT findings, and the possibility of bias due to large drop-out rates, have been questioned,4 similar results were found in a substudy of the large US ACTG 5202 study. Participants in this clinical trial were randomised to either Truvada or Kivexa, plus either ritonavir-boosted atazanavir or efavirenz. At 96 weeks, BMD loss was significantly larger with Truvada than with Kivexa (-1.3 vs -3.0% for lumbar spine; -2.6 vs -3.9% for hip).5

In the ASSERT study and in all four regimens of ACTG 5202, BMD declined sharply soon after starting treatment, then stabilising or even rising somewhat (although still below baseline levels) after roughly one year. In the ACTG study, BMD began to decrease again near week 144.

References

  1. Cassetti I et al. The safety and efficacy of tenofovir DF in combination with lamivudine and efavirenz through 5 years in antiretroviral-naïve patients. Eighth International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, San Francisco, poster 82, 2006
  2. Verhelst D et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis 40: 1331-1333, 2002
  3. Stellbrink HJ et al. Comparison of changes in bone density turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results of from the Asset study. Clin Infect Dis, 51: 963-72, 2010
  4. Carr A and Hoy J Low bone mineral density with tenofovir: does statistically significant mean clinical significance? Clin Infect Dis, 51, 973-75, 2010
  5. McComsey G et al. Bone and limb fat outcomes of ACTG A5224s, a substudy of ACTG A5202: a prospective, randomized, partially blinded phase III trial of ABC/3TC or TDF/FTC with EFV or ATV/r for initial treatment of HIV-1 infection. Seventeenth Conference on Retroviruses and Opportunistic Infections, abstract 106LB, San Francisco, 2010
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