Tenofovir use is Associated with an Increase in Serum Alkaline Phosphatase in the Swiss HIV Cohort Study
Abstract
Background Tenofovir (TDF) use has been associated with proximal renal tubulopathy, reduced calculated glomerular filtration rates (cGFR) and losses in bone mineral density. Bone resorption could result in a compensatory osteoblast activation indicated by an increase in serum alkaline phosphatase (sAP). A few small studies have reported a positive correlation between renal phosphate losses, increased bone turnover and sAP. Methods We analysed sAP dynamics in patients initiating (n=657), reinitiating (n=361) and discontinuing (n=73) combined antiretroviral therapy with and without TDF and assessed correlations with clinical and epidemiological parameters. Results TDF use was associated with a significant increase of sAP from a median of 74 U/l (interquartile range 60–98) to a plateau of 99 U/l (82–123) after 6 months (P<0.0001), with a prompt return to baseline upon TDF discontinuation. No change occurred in TDF-sparing regimes. Univariable and multivariable linear regression analyses revealed a positive correlation between sAP and TDF use (P≤0.003), but no correlation with baseline cGFR, TDF-related cGFR reduction, changes in serum alanine aminotransferase (sALT) or active hepatitis C. Conclusions We document a highly significant association between TDF use and increased sAP in a large observational cohort. The lack of correlation between TDF use and sALT suggests that the increase in sAP is because of the bone isoenzyme and indicates stimulated bone turnover. This finding,…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 657 participants or records.
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