Higher rate of renal impairment in a regimen of tenofovir/lamivudine/nevirapine compared to tenofovir/lamivudine/efavirenz
Background: During stavudine phase-out plan in developing countries, tenofovir has been used to substitute stavudine. However, knowledge regarding whether there is any difference of the frequency of renal injury between tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) and tenofovir/lamivudine/nevirapine (TDF/3TC/NVP) is lacking.
Methods: A prospective study was conducted among HIV-infected patients who were switched NRTI backbone from stavudine/lamivudine to tenofovir/lamivudine in efavirenz-based regimen (TDF/3TC/EFV group) and nevirapine-based regimen (TDF/3TC/NVP group) after two years of an ongoing randomized trial. All patients were assessed at time of switching, 12 and 24 weeks for serum phosphorus, uric acid, creatinine, estimated glomerular filtration rate (eGFR) by modification of diet in renal disease equation, and urinalysis.
Results: Of 62 patients, 28 patients were in TDF/3TC/EFV group and 34 patients were in TDF/3TC/NVP group. There were no significant differences in demographic characteristics at the time of switching (P >0.05). At 12 weeks, comparing [mean±SD or median (IQR)] measures between TDF/3TC/EFV group and TDF/3TC/NVP group were: phosphorus of 3.16±0.53 vs. 2.81±0.42 mg/dL (P=0.005), uric acid of 5.53±1.38 vs. 5.03±1.23 mg/dL (P=0.136), eGFR of 116 (98-134) vs. 105 (88-123) mmol/min (P=0.270), creatinine of 0.78±0.14 vs. 0.84±0.19 mg/dL (P=0.115), %patients with proteinuria were 15% vs. 38% (P=0.050). At 24 weeks, [mean±SD or median (IQR)] measures between the corresponding groups were: phosphorus of 3.26±0.78 vs. 2.84±0.47 mg/dL (P=0.011), uric acid of 5.05±1.13 vs. 4.73±1.17 mg/dL (P=0.324), eGFR of 110 (99-121) vs. 98 (83-112) mmol/min (P=0.008), creatinine of 0.78±0.16 vs. 0.86±0.19 mg/dL (P=0.075), % patients with proteinuria were 18% vs. 35% (P=0.159). In TDF/3TC/NVP group, comparing week 12 to time of switching, there was a decrement of phosphorus (P=0.007) and decrement of eGFR (P=0.034). No patient developed acute renal failure.
Conclusions: The frequency of tenofovir-associated renal impairment was significantly higher in patients receiving tenofovir/lamivudine/nevirapine compared to tenofovir/lamivudine/efavirenz. Further studies regarding patho-physiology of the renal impairment in tenofovir/lamivudine/nevirapine is warranted.
W. Manosuthi1,2, A. Lueangniyomkul1, W. Mankatitham1, W. Prasithsirikul1, P. Tantanathip1, A. Narkksoksung1, S. Nilkamhang1, S. Sungkanuparph2
1Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand, 2Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand