Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial.
BACKGROUND
There are 2 once-daily, fixed-dose-combination, dual-nucleoside analogue tablets: tenofovir 300 mg-emtricitabine 200 mg (TDF-FTC) and abacavir 600 mg-lamivudine 300 mg (ABC-3TC). Which fixed-dose-combination tablet is more effective and safe is uncertain.


METHODS
We compared TDF-FTC and ABC-3TC in a randomized, open-label, 96-week trial in which either fixed-dose-combination was substituted for current nucleoside treatments in human leukocyte antigen-B*5701-negative adults with human immunodeficiency virus loads <50 copies/mL. The primary end point was virological failure (consecutive viral load measurements >400 copies/mL, by intention-to-treat). Secondary end points included death, AIDS, adverse events, serious non-AIDS events, metabolic parameters, and body composition. We used exact statistics for differences in proportions, T tests to compare means, and Cox regression for hazard ratios.


RESULTS
Of 441 patients who were screened, 357 were treated; 98% were men, the mean age was 45 years, 30% were receiving TDF, 20% were receiving ABC, and 24% were receiving a protease inhibitor. Virological failure was uncommon (5.6% for ABC-3TC and 3.9% for TDF-FTC; difference, 1.7%; 95% confidence interval [CI], -2.8% to 6.1%; P = .62). No participant developed AIDS, whereas 18 (5%) participants developed a serious non-AIDS event (rate, 2.79 events per 100 person-years; 95% CI, 1.76-4.43), of which 4 were fatal. TDF-FTC was associated with significantly fewer serious non-AIDS events than ABC-3TC (1.2 vs 4.8 events per 100 patient-years; hazard ratio [HR], 0.24; 95% CI, 0.08-0.73; P = .012), influenced mostly by a lower rate of cardiovascular events (0.3 vs 2.2 events per 100 patient-years; HR, 0.12; 95% CI, 0.02-0.98; P = .048). TDF-FTC resulted in significantly lower bone mineral density (mean difference in hip t score, 0.16; 95% CI, 0.08-0.23; P < .001) but not in more fractures.


CONCLUSIONS
In this population, TDF-FTC and ABC-3TC had similar virological efficacy, but ABC-3TC was associated with more serious non-AIDS events, particularly cardiovascular events. Clinical trials registration. NCT00192634 .
Martin
Allison
A
National Centre in HIV Epidemiology and Clinical Research UNSW, 5St Vincent's Centre for Applied Medical Research, Sydney, Australia.
Bloch
Mark
M
Amin
Janaki
J
Baker
David
D
Cooper
David A
DA
Emery
Sean
S
Carr
Andrew
A
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015224:Dideoxynucleosides; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D015235:HLA-B Antigens; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; C484830:HLA-B*57:01 antigen; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir