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Kidney Function Improves With TDF-to-ABC Switch Regardless of Atazanavir Use
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7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Renal function measured several ways improved after people on a suppressive tenofovir (TDF)-containing regimen switched to an abacavir (ABC) regimen, regardless of whether they were taking the protease inhibitor atazanavir [1]. Viral control remained stable after the switch and CD4 counts rose.
Numerous studies indicate that renal function improves when a person replaces tenofovir with another drug, often abacavir. But atazanavir also affects kidney function, and the impact of switching from tenofovir in people who continue atazanavir was not well understood until this retrospective analysis in Vancouver, British Columbia.
The study involved HIV-positive men and women at least 19 years old and taking a stable tenofovir-containing regimen plus either emtricitabine or lamivudine. Everyone had a viral load below 200 copies for at least 3 months before swapping tenofovir for abacavir and retaining the third drug in their regimen.
The researchers recorded the worst values for creatinine, estimated glomerular filtration rate (eGFR), phosphorous, urine albumin-to-creatinine ratio, and lipids in the 12 months before the switch from tenofovir and at the dates closest to 3, 6, and 12 months after the switch. They recorded the CD4 count and viral load immediately before the switch and afterwards.
The study group included 225 people, 45 of them (20%) women and 126 (56%) taking atazanavir at the time of the switch. Median age at the switch was 47 (interquartile range [IQR] 42 to 55) and median CD4 count 440 (IQR 310 to 620). Everyone had a viral load below 200 copies just before trading tenofovir for abacavir.
Preswitch creatinine fell from a median of 100 umol/L to 90 at 3 months, 89 at 6 months, and 87 at 12 months, all significant declines (P < 0.001). Median eGFR before the switch and at 3, 6, and 12 months afterwards was 69, 78, 81, and 81 mL/min, and again all the postswitch improvements were statistically significant (P < 0.001). Likewise, urine albumin-to-creatinine ratio and phosphorus improved significantly at all three postswitch points (P < 0.001 for all comparisons).
Median CD4 counts rose from 440 on tenofovir to 460 at 3 months (P < 0.01), 520 at 6 months (P < 0.001), and 505 at 12 months (P < 0.001). Whereas everyone had a viral load below 200 copies before switching from tenofovir, 99.4%, 97.8%, and 98.4% did 3, 6, and 12 months after the switch, and these changes were not statistically significant.
Next the researchers repeated those analyses for the 126 people taking atazanavir as their third drug and for the 99 taking some other third antiretroviral. Posttenofovir improvements in the four renal measures were largely similar in the two groups at the 3-, 6-, and 12-month follow-ups. The only significant difference resulted from a 3-month worsening in urine albumin-to-creatinine ratio in the nonatazanavir group. At the 6-month and 12-month follow-ups, this ratio improved from the preswitch reading in the nonatazanavir group and was similar to the improvement in the atazanavir group.
The only lipid parameter to change significantly after the switch from tenofovir was "good" high-density lipoprotein cholesterol, which rose significantly 3, 6, and 12 months after people started abacavir.
The researchers noted that their analysis is limited by its retrospective nature, relatively small sample size, and lack of access to complete clinical data. With those limitations in mind, they believe their results "demonstrate that switching from tenofovir to abacavir-based HAART is effective, safe and also improves renal function parameters among patients who are responding to tenofovir-based HAART regardless of whether they are also on atazanavir."
Reference
1. Harris M, Guillemi S, Chan K, et al. Effects on renal function of a switch from tenofovir (TDF)- to abacavir (ABC)-based highly active antiretroviral therapy (HAART), with or without atazanavir. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur.
Abstract WEAB0202. http://pag.ias2013.org/session.aspx?s=59
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