SUMMARY: HIV/HBV coinfected patients who have advanced liver fibrosis are at significantly greater risk for developing kidney function impairment while taking tenofovir (Viread, also in the Truvada and Atripla coformulations), according to research presented at the recent American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) in Boston. These findings led researchers to recommend that people with advanced fibrosis or cirrhosis (stage F3-F4) should received more intensive kidney function monitoring than those with milder liver disease.

By Liz Highleyman

Tenofovir has potent activity against both HIV and hepatitis B virus (HBV), and treatment guidelines recommend that coinfected patients should include the drug as part of their antiretroviral regimen. Long-term use of tenofovir has been linked to kidney dysfunction in a small proportion of people with HIV alone, but this has not been extensively studied in HIV/HBV coinfected individuals.

In the present analysis, Anders Boyd from Hopital Saint-Antoine in Paris and colleagues looked at liver fibrosis as a risk factor for kidney dysfunction while on tenofovir. The study included 137 treatment-experienced patients (88% men, average age about 42 years) who started tenofovir and were followed for a median of about 33 months.

Liver fibrosis stage at baseline was estimated using a combination of blood biomarkers known as FibroMeter. Participants were classified as having absent-to-moderate fibrosis (equivalent to Metavir stage F0-F2) versus advanced fibrosis or cirrhosis (stage F3-F4).

Glomular filtration rate (GFR), an indicator of kidney function reflecting creatinine clearance, was estimated using the CKD-EPI equation at the start of treatment and averaged for every subsequent 6-month interval (expressed as mL/min/1.73m2). During follow-up, changes in GFR were stratified according to baseline fibrosis status.

Results

	Overall, average changes in GFR from baseline were +0.6, +0.9, and -0.2, respectively, after 12, 24, and 36 months on tenofovir.
	The 41 patients with advanced fibrosis when they started tenofovir experienced a much steeper decline in creatinine clearance than those with milder fibrosis.
	In the advanced fibrosis group, the maximum average GFR decrease was -6.3 after 18 months, while the overall decrease was -4.5.
	No such effect was seen, however, for the 96 participants with milder baseline fibrosis, with GFR changes of +0.6 after 18 months and -0.8 after 36 months.
	Significant differences in kidney function between the advanced and milder fibrosis groups were observed at 12, 18, and 24 months after tenofovir initiation.
	In a multivariate analysis, patients with stage F3-F4 fibrosis had a 3.74-fold higher risk of mild kidney impairment than people with lower fibrosis score after adjusting for age, sex, race, HIV viral load, CD4 cell count, duration of HBV infection, and concurrent use of protease inhibitors.

Based on these findings, the researchers concluded, "HIV/HBV coinfected patients treated with tenofovir are at higher risk of [kidney] impairment when exhibiting high liver fibrosis level (> F3), thereby warranting a closer follow-up of GFR in this patient population."

Investigator affiliations: Infectious Diseases Unit, Hôpital Saint-Antoine, INSERM U707, Paris, France; Hepatology, Hôtel-Dieu, Hospices Civils de Lyon, Lyon, France.

11/12/10

Reference
A Boyd, J Bottero, C Lascoux-combe, and others. Significant liver fibrosis is an independent risk factor of renal impairment in HIV-HBV co-infected patients treated with tenofovir (TDF): results of a 3-year-cohort study. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 388.