Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study.
BACKGROUND
Abacavir/lamivudine and tenofovir/emtricitabine fixed-dose combinations are commonly used first-line antiretroviral therapies, yet few studies have comprehensively compared their safety profiles.


METHODS
Forty-eight-week data are presented from this multicenter, randomized, open-label study comparing the safety profiles of abacavir/lamivudine and tenofovir/emtricitabine, both administered with efavirenz, in HLA-B*5701-negative HIV-1-infected adults.


RESULTS
Three hundred eighty-five subjects were enrolled in the study. The overall rate of withdrawal was high (28%). Changes in estimated glomerular filtration rate from baseline were similar between arms [difference 0.953 mL.min.1.73 m (95% confidence interval: -1.445 to 3.351), P = 0.435]. Urinary excretion of retinol-binding protein and beta-2 microglobulin increased significantly more in the tenofovir/emtricitabine arm (+50%; +24%) compared with the abacavir/lamivudine arm (no change; -47%) (P < 0.0001). A lower proportion achieved viral load <50 copies per milliliter in the abacavir/lamivudine arm (114 of 192, 59%) compared with the tenofovir/emtricitabine arm (137 of 193, 71%) [difference 11.6% (95% confidence interval: 2.2 to 21.1)]. The overall virological failure rate was low. The adverse event rate was similar between arms (except drug hypersensitivity, reported more in the abacavir/lamivudine arm).


CONCLUSIONS
The study showed no difference in estimated glomerular filtration rate between the arms, however, increases in markers of tubular dysfunction were observed in the tenofovir/emtricitabine arm, the long-term consequence of which is unclear. A significant difference in efficacy favoring tenofovir/emtricitabine was observed.
Post
Frank A
FA
King's College London, London, United Kingdom.
Moyle
Graeme J
GJ
Stellbrink
Hans Jürgen
HJ
Domingo
Pere
P
Podzamczer
Daniel
D
Fisher
Martin
M
Norden
Anthony G
AG
Cavassini
Matthias
M
Rieger
Armin
A
Khuong-Josses
Marie-Aude
MA
Branco
Teresa
T
Pearce
Helen C
HC
Givens
Naomi
N
Vavro
Cindy
C
Lim
Michael L
ML
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D012177:Retinol-Binding Proteins / Q000652:urine; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D001613:beta 2-Microglobulin / Q000652:urine; D000099227:Abacavir
D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D012177:Retinol-Binding Proteins; D000068698:Tenofovir; D001613:beta 2-Microglobulin; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C098320:efavirenz