Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C.

Abstract

Fibroblast growth factor 23 (FGF23) has been associated with cardiovascular mortality. We estimate associations between the level of plasma FGF23 and exposure to abacavir (ABC) and to other components of antiretroviral therapy in patients co-infected with HIV and hepatitis C. Both intact and c-terminal FGF23 were measured in plasma using commercial assays for a sub-cohort of 295 patients selected at random from the 1150 patients enrolled in the Canadian Co-infection Cohort. The multiplicative effects of antiretroviral drug exposures and covariates on median FGF23 were then estimated using a hierarchical Bayesian model. The median level of intact FGF23 was independent of either past or recent exposure to abacavir, with multiplicative ratios of 1.00 and 1.07, 95% credible intervals 0.90-1.12 and 0.94-1.23, respectively. Median intact FGF23 tended to increase with past use of both nonnucleoside reverse-transcriptase inhibitors and protease inhibitors, but tended to decrease with recent use of either tenofovir, efavirenz or lopinavir. There were no obvious associations between the median level of c-terminal FGF23 and individual drugs or drug classes. Age, female gender, smoking and the aspartate aminotransferase to platelet ratio index were all associated with a higher median c-terminal FGF23 but not with a higher median intact FGF23. The level of FGF23 in plasma was independent of exposure to ABC. Lower levels of intact FGF23 with recent use of tenofovir, efavirenz or lopinavir may reflect their adverse effects on bone and vitamin D metabolism relative to other drugs in their respective drug classes.