6th IAS Conference On HIV Pathogenesis, Treatment and Prevention

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A comparative analysis of risk factors associated with efavirenz, darunavir/ritonavir, lopinavir/ritonavir, atazanavir/ritonavir and renal impairment

N. Rockwood, M. Nelson, S. Mandalia, B. Gazzard

Chelsea and Westminster, HIV/GUM, London, United Kingdom

Background: The long term effect of Protease Inhibitors(PIs) on renal function is unknown. We compared the effect of efavirenz(EFV) and boosted PIs atazanavir(ATZ), lopinavir(LPV) and darunavir(DRV) on reaching first eGFR< 60.
Methods: 2115 patients were prescribed HAART containing 2NRTI+ EFV or PIs and had a baseline eGFR available between 06/06-02/10. Univariate and adjusted Cox's hazards regression model were used to show likelihood of renal impairment (eGFR< 60). Proportion of renal recovery after first eGFR< 60 was examined.
Results: 386(18%) reached eGFR< 60. On univariate analysis, female gender(HR 1.51,p0.002), baseline age(p< 0.001), baseline eGFR(p< 0.001),DRV(HR1.53,p< 0.001), ATZ(HR 1.27,p0.036), LPV(HR 1.71,p< 0.001), prior Tenofovir(TFV) exposure(HR 1.68,p< 0.001), Hep B Sag +ve status(HR1.21,p< 0.001) and total duration TFV exposure(HR 1.09,p< 0.001) were associated with significantly increased risk of eGFR< 60. Ethnicity, baseline CD4 count, baseline viral load(VL), VL blips >500, prior EFV exposure and Hep C+ve status were not. EFV was linked with significantly decreased risk of eGFR< 60(HR 0.6,p< 0.001). Risk of eGFR< 60 increased by 9% per year exposure to TFV. Multivariate analysis with comparison to EFV showed DRV(HR 1.3,p0.014) and LPV(HR 1.8,p< 0.001) but not ATZ to have significantly increased risk of eGFR< 60. There were no significant differences between the EFV group(N=50) and PI group(N=160) in a subgroup analysis of traditional risk factors for renal impairment. Post first eGFR< 60, at 12months, 50% of patients had eGFR>60. Between 0-30months, there was a mean 31% increase in proportion of patients with renal recovery in those who stopped TFV compared to those who continued TFV(p< 0.001).
Conclusion: There was significant risk of renal impairment with boosted LPV and DRV in the study. The effect of boosted ATZ on renal impairment was no longer significant after adjusting for TFV exposure. In individuals developing eGFR< 60, cessation of TFV was associated with higher rate of renal recovery.


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