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Switching From TDF/FTC to Raltegravir Improves Kidney Markers
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51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
Substituting the integrase inhibitor raltegravir for tenofovir/emtricitabine (TDF/FTC) decreased proteinuria and increased glomerular filtration rate (GFR) in an observational study of 21 US patients [1]. These markers did not improve in 6 people, and 1 person had virologic failure after the switch.
Decreased GFR and increased proteinuria are well-documented side effects of tenofovir. To determine whether substituting raltegravir for TDF/FTC can reverse proteinuria while maintaining virologic suppression, investigators in San Francisco and Long Beach, California planned this prospective, two-center, observational study.
The 21 study participants had a viral load below 200 copies for more than 12 weeks while taking TDF/FTC plus a ritonavir-boosted protease inhibitor (PI). Everyone had proteinuria that could be attributed only to tenofovir. No one had a history of PI failure, no one had taken an integrase inhibitor, and no one had hepatitis B infection. Study participants kept the same PI when swapping TDF/FTC for raltegravir.
Nineteen study participants were men, and the group had been infected with HIV for an average of 8 years. CD4 count at study entry averaged 546 (range 167 to 895), 8 participants had well-controlled hypertension, and 1 had well-controlled diabetes. TDF use averaged 45 months (range 6 to 85). Initial urine protein averaged 48.3 mg/dL (range 7 to 154), while urine protein clearance averaged 323 mg/g (range 99 to 1878).
Acute renal failure developed in one person 4 weeks after the switch to raltegravir, and that person is not included in analyses of urine protein and GFR.
Twenty-four weeks after the switch to raltegravir, urine protein fell by an average 10.8 mg/dL. Fourteen participants had drops in proteinuria (average -19.9 mg/dL, range -1.1 to -51.8) and 6 did not (average +5.7 mg/dL, range +2.9 to +11.9). Urine protein clearance dropped by an average 86 mg/g. Fourteen people had declines in protein urine clearance (average -122 mg/g, range -4 to -394) and 6 had increases (average +21 mg/g, range +3 to +37).
Cockroft-Gault-calculated GFR rose by an average 17.5 mL/min (range 2 to 63), and GFR increased in everyone who completed the study.
One person suffered virologic failure with a viral load of 1620 copies at week 24. Genotyping disclosed emergence of an integrase mutation in this person's virus. All other study participants maintained a viral load below 200 copies. CD4 counts rose by an average 24 cells during the 24-week study, but the CD4 change varied widely in these people, from a 366-cell drop to a 469-cell jump.
Reference
1. Bredeek F, Guadron R, Yolo R, Schneider S. A switch from TDF/FTC to raltegravir in patients on a boosted protease inhibitor is effective in reducing proteinuria and increasing GFR. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H1-1399b.
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