SUMMARY: HIV/HBV coinfected people with advanced fibrosis are more likely to experience impaired kidney function while taking tenofovir (Viread, also in the Truvada and Atripla combination pills), according to a poster presented at the 18th Conference on Retroviruses and Opportunistic Infection (CROI 2011) last month in Boston. Investigators recommended that coinfected patients with stage F3 or high fibrosis should therefore receive more frequent kidney function monitoring.

By Liz Highleyman

Tenofovir has good antiviral activity against both HIV and hepatitis B virus (HBV), so treatment guidelines recommend it as a preferred antiretroviral option for people with HIV/HBV coinfection. But tenofovir has been shown to cause kidney toxicity in susceptible individuals.

Anders Boyd, K. Lacombe, and colleagues conducted a study to assess kidney impairment and its association with liver disease in HIV/HBV coinfected people. Unlike many antiretroviral drugs, tenofovir is mainly processed by the kidneys, rather than the liver. Nevertheless, liver damage can lead to impaired blood flow and buildup of toxins that can have a detrimental effect on kidney function.

This analysis included 137 treatment-experienced patients enrolled in the French HIV-HBV Cohort Study between 2002 and 2006 who started tenofovir and used the drug for at least 6 months (mean 32 months). Nearly 90% of participants were men and the average age was about 42 years.

The researchers looked at creatinine clearance, a laboratory measure of kidney function, at the time of tenofovir initiation and every 6 months thereafter. Creatinine clearance levels were averaged for each 6-month interval. They estimated changes over time, adjusting for factors including age, sex, race, HIV viral load, CD4 cell count, and use of protease inhibitors.

Mild kidney function impairment was defined as an estimated glomerular filtration rate (eGFR, using the CKD-EPI equation) < 80, with severe impairment < 50. Median eGFR was 99.3 at the time of tenofovir initiation.

Liver fibrosis stage was estimated using Fibrometer scores derived from a set of biomarker measurements. Patients were classified as having either absent-to-moderate fibrosis (equivalent to Metavir stages F0-F2; 96 patients) or advanced fibrosis (stages F3-F4; 41 patients).

Results

	Overall, average eGFR was 97.1 after 12 months on tenofovir, 98.6 after 24 months, and 95.3 after 36 months.
	Patients with higher fibrosis scores when they started tenofovir experienced "much steeper" declines in creatinine clearance, with maximum average eGFR decreases of -6.3 after 18 months and -4.5 after 36 months.
	No such decline was seen among patients with low baseline fibrosis scores, with average changes of +0.6 after 18 months and -0.8 after 36 months.
	Significant differences between the mild and advanced fibrosis groups were observed at 12, 18, and 24 months after starting tenofovir.
	56 people transitioned from normal to mildly impaired kidney function during follow-up.
	In a multivariate analysis, patients with F3-F4 fibrosis had a 3.74-fold higher risk of developing mild kidney impairment than people with lower fibrosis scores, after adjusting for other factors.
	Participants who went from normal to impaired kidney function spent an average of 8.6 months with creatinine clearance < 80.

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

Investigator affiliations: INSERM UMR S707, Paris, France; Hosp St Antoine, Paris, France; Univ Pierre and Marie Curie, Paris, France; Hosp St Louis, Paris, France; Hospices Civils de Lyon, France.

3/18/11

Reference
K Lacombe, Anders Boyd, E Lasnier, et al. Significant Liver Fibrosis Is an Independent Risk Factor of Renal Impairment in HIV/HBV Co-infected Patients Treated with TDF: Results of a 3-Year Cohort Study. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston. February 27-March 2, 2011. Abstract 977.