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Fibrosis Predicts Renal Trouble With Tenofovir in HIV/HBV-Coinfected
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
F3 or F4 liver fibrosis independently raised the risk of renal impairment in tenofovir-treated people coinfected with HIV and HBV, according to results of a 3-year study in France [1]. The investigators advised that tenofovir-treated coinfected people with fibrosis need closer monitoring of creatinine clearance.
This multicenter prospective study involved 137 people recruited for the French HIV-HBV Cohort Study from 2002 through 2006. To be eligible for this analysis, HIV-positive people needed a positive HBV surface antigen (HBsAg) test, at least 6 months of tenofovir experience, and at least two samples available for creatinine and liver fibrosis evaluation.
To quantify fibrosis level, the investigators figured Metavir equivalents of Fibrometer score according to previously validated levels in HIV/HBV-coinfected people. They calculated estimated glomerular filtration rate (eGFR) by the CKD-EPI equation when tenofovir therapy began and averaged values for 6-month intervals. They used the CKD-EPI equation because they believe it estimates eGFR better at higher creatinine levels.
The researchers used general estimating equations to model the change in eGFR from baseline at each interval with adjustment for age, gender, black race, median baseline GFR, HIV load, and protease inhibitor experience. They then stratified eGFR by baseline fibrosis level, dividing cohort members into those Fibrometer F3-F4 versus F0-F2 Metavir equivalents.
There were 41 people in the F3-F4 group and 96 in the F0-F2 group. Everyone in F3-F4 was a man, while 16 in F0-F2 (17%) were women (P = 0.003). Average age was significantly older in the F3-F4 group (44.3 versus 40.6, P = 0.01). A lower proportion of people with F3-F4 fibrosis were positive for hepatitis B e antigen, which suggests a person is infectious (48.8% versus 69.8%, P = 0.02). The groups did not differ significantly in HIV load, duration of HIV or HBV infection, proportion treated with lamivudine or pegylated interferon (7.3% F3-F4 versus 1% F0-F2, P = 0.08), or alcohol consumption.
Among all study participants, median eGFR stood at 99.3 mL/min/1.73m(2) when tenofovir began. Only 1 person had severe renal impairment, defined as a level below 50 mL/min/1.73m(2), when follow-up began. Overall median eGFR at months 12, 24, and 36 of tenofovir therapy measured 97.1, 98.6, and 95.3 mL/min/1.73m(2).
People with F3-F4 fibrosis when tenofovir began had much steeper drops in eGFR, with nadir changes averaging -6.3 mL/min/1.73m(2) after 18 months of tenofovir (P = 0.001) and -4.5 mL/min/1.73m(2) after 36 months (P = 0.04). Average values in the F0-F2 group did not change significantly over time. eGFR differed significantly between the two fibrosis groups at months 12 (P < 0.05), 18 (P = 0.005), and 24 (P = 0.03).
Evaluating 721 eGFR measurements, the investigators counted 56 transitions from normal renal function at baseline (at or above 80 mL/min/1.73m2) to mild impairment (below 80) during follow-up. A multivariate model to identify predictors of transition from normal renal function to mild renal impairment adjusted for age, gender, place of birth (Europe or Africa), undetectable HIV load, CD4 count above 250, estimated duration of HIV infection, and protease inhibitor use.
Having F3-F4 fibrosis almost quadrupled the risk of transition from normal renal function to mild impairment (adjusted hazard ratio 3.74, 95% confidence interval 1.57 to 8.92). Age younger than the group median of 40.6 years lowered the risk of worsening renal function about 75% (adjusted hazard ratio 0.24, 95% confidence interval 0.07 to 0.81).
The researchers concluded that HIV/HBV-coinfected tenofovir-treated people "are at higher risk of renal impairment when exhibiting high liver fibrosis level (>/= F3), thereby warranting a closer follow-up of creatinine clearance."
Reference
1. Lacombe K, Anders Boyd A, Lasnier E, 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. February 27-March 2, 2011. Boston. Abstract 977.
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