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Assessment of Renal Findings of Abacavir/Lamivudine (ABC/3TC) Compared to Tenofovir/Emtricitabine
(TDF/FTC) in Combination with QD Lopinavir/Ritonavir (LPV/r) Over 96 Weeks in the HEAT Study
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Reported by Jules Levin
CROI 2009 Feb 8-12 2009 Montreal
Derek Fine1, Kimberly Y. Smith2, Parul Patel3, Nicholaos C. Bellos4, Louis Sloan5, Phillip Lackey6, Princy N. Kumar7, Denise H. Sutherland-Phillips3, Linda Yau3, and Mark S. Shaefer3
1Johns Hopkins School of Medicine, Baltimore, MD, US; 2Rush University Medical Ctr, Chicago, IL, US; 3GSK, RTP, NC, US; 4SW Infectious Disease Associates, Dallas, TX, US; 5North Texas Infectious Disease Consultants, Dallas, TX, US; 6ID Consultants, Charlotte, NC, US; 7Georgetown University, Washington, D.C., US
AUTHOR CONCLUSIONS
Absolute differences in renal function as estimated by eGFR and eCrCl were small between ABC/3TC and TDF/FTC each coadministered with LPV/r over 96 weeks.
TDF/FTC-treated subjects were more likely to experience any renal adverse event compared to ABC/3TC-treated subjects.
Progression to CKD stage 3 (eGFR <60mL/min/1.732) occurred more often in TDF/FTC-treated subjects.
Routine renal monitoring can detect overt or antiretroviral-induced kidney disease earlier and should be considered in all patients commencing antiretroviral therapy.
AUTHOR DISCUSSION
Renal disease and its complications are important to consider and likely to increase due to increasing life expectancy afforded by HAART and the ageing of HIV-infected patients.
Limited data are available to help practitioners determine which patients are at highest risk for antiretroviral-induced renal toxicity and how often to assess for toxicity.
Results showed that improvement in renal function, as measured by eGFR and CrCl, was slightly greater, though small in absolute terms, with ABC/3TC compared to TDF/FTC over 96 weeks.
More subjects in the TDF/FTC arm had treatment-related renal adverse events over 96 weeks including 5 subjects with PRTD. In most subjects with adverse renal events, confounding medical history or use of nephrotoxic concomitant meds was not a contributing factor thus complicating the identification of patients at highest risk.
Progression to a more advanced stage of CKD (eGFR <60mL/min/1.732) occurred more often in subjects receiving TDF/FTC.
As HIV-infected patients advance into older age and exhibit declines in renal function, selection of antiretroviral therapy may become more complicated.
All subjects experiencing renal dysfunction required closer follow-up and repeat laboratory testing. Early consult with a nephrologist is suggested for patients with changing renal function.
INTRODUCTION
HAART has resulted in dramatic improvements in morbidity and mortality shifting the focus to long-term management of HIV and co-morbid conditions such as renal dysfunction.
HIV infection, host factors, specific antiretrovirals, and concomitant nephrotoxic drugs all may contribute to the increasing prevalence of renal disease in the U.S.
We compared the of the renal effects of ABC/3TC vs. TDF/FTC each with LPV/r in HIV-1 infected, antiretroviral-naive subjects enrolled in the HEAT study over 96 weeks.
RENAL DISEASE & HIV INFECTION
Renal function is estimated to be abnormal in up to 30% of HIV-infected
patients, however, patients are usually asymptomatic unless in advanced stages.1
Risk factors for kidney disease in the HIV-infected population include: hypertension, diabetes, black race, host factors, hepatitis C infection, lower CD4+ count and higher VL.1
Baseline assessment of risk factors for chronic kidney disease, urine analysis (for proteinuria) and serum creatinine (for estimate of Clcr or GFR) is recommended for all HIV-1 infected patients.1
Drug-induced renal dysfunction has been reported with the use of certain antiretrovirals, notably tenofovir and indinavir.2
Tenofovir has been variably associated with a range of renal disturbances
from decreased creatinine clearance to proximal renal tubule damage.
-- Zimmermann et al. found tenofovir-associated acute renal failure to be commonly associated with use of the boosted PI, LPV/r.3
-- Kiser et al. reported a 17.5% decrease in TFV clearance when coadministered with LPV/r after adjustment for renal function.4
In contrast with tenofovir, abacavir has been rarely associated with renal dysfunction likely due to its negligible renal elimination (<2%).5
REFERENCES
1. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005;40:1559-1585.
2. Post FA and Holt SG. Recent developments in HIV and the kidney. Curr Opin Infect Dis 2009; 22:43-48.
3. Zimmermann AE, Pizzoferrato T, Bedford J et al. Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis 2006;42:283-290.
4. Kiser JJ, Carten ML, Anderson PL, et al. The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharm Ther 2008;83:265-272.
5. Izzedine H, Launay-Vacher V, Aymard G, et al. Pharmacokinetics of abacavir in HIV-1 infected patients with impaired renal function. Nephron 2001;89:62-67.
6. Fisher EJ, Chaloner K, Cohn DL et al. The safety and efficacy of adefovir disoproxil in patients with advanced HIV disease: a randomized, placebo-controlled trial. AIDS 2001;15:1695-1700.
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