Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial.
BACKGROUND
Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral load.


METHODS
This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks calculated with Cockcroft-Gault equation.


RESULTS
58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3 (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026). Per protocol analysis showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms (24 in RAL+DRV and 29 in LPV/r+TVD).


CONCLUSIONS
Switching LPV/r+TVD to RAL+DRV/r did not significantly increase the proportion of patients who showed >10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load.


BACKGROUND
ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J).
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
Takeshi
T
Nishijima
Hiroyuki
H
Gatanaga
Takuro
T
Shimbo
Hirokazu
H
Komatsu
Tomoyuki
T
Endo
Masahide
M
Horiba
Michiko
M
Koga
Toshio
T
Naito
Ichiro
I
Itoda
Masanori
M
Tei
Teruhisa
T
Fujii
Kiyonori
K
Takada
Masahiro
M
Yamamoto
Toshikazu
T
Miyakawa
Yoshinari
Y
Tanabe
Hiroaki
H
Mitsuya
Shinichi
S
Oka
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069454:Darunavir; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007677:Kidney Function Tests; D061466:Lopinavir / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D063065:Organophosphonates; D011760:Pyrrolidinones; D013449:Sulfonamides; D003841:Deoxycytidine; D061466:Lopinavir; D000068898:Raltegravir Potassium; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069454:Darunavir