Short-term safety and tolerability of a once-daily fixed-dose abacavir-lamivudine combination versus twice-daily dosing of abacavir and lamivudine as separate components: findings from the ALOHA study.
OBJECTIVE
To evaluate the short-term (12 wks) safety and tolerability of a once-daily, fixed-dose abacavir-lamivudine combination versus twice-daily dosing of the separate components, both with background antiretroviral therapy.


METHODS
Phase IIIB, randomized, open-label, parallel-group, multicenter study.


METHODS
One hundred forty-six human immunodeficiency virus (HIV) clinics.


METHODS
Six hundred eighty antiretroviral therapy-naïve patients with HIV type 1 RNA greater than 1000 copies/ml at baseline.


METHODS
Patients were randomly assigned in a 2:1 manner to receive either abacavir 600 mg-lamivudine 300 mg once/day or abacavir 300 mg twice/day and lamivudine 150 mg twice/day. Subjects were stratified based on choice of third or fourth antiretroviral drug (nucleoside reverse transcriptase inhibitor [NRTI], NNRTI, or protease inhibitor), assigned before randomization.


RESULTS
The primary end point was occurrence of grades 2-4 adverse events and serious adverse events; abacavir hypersensitivity reactions were considered serious adverse events. Baseline characteristics were similar between the once-daily (455 patients) and twice-daily (225 patients) groups. The rates of all grades 2-4 adverse events were similar: once-daily 33% (150 patients), twice-daily 31% (69). A slightly larger proportion of patients in the twice-daily group experienced drug-related grades 2-4 adverse events: once-daily 10% (47), twice-daily 16% (36). Rates of all serious adverse events (once-daily 11% [49], twice-daily 10% [22]) and drug-related serious adverse events (once-daily 5% [21], twice-daily 8% [17]) were similar. The rate of suspected abacavir hypersensitivity reaction was 5.3% (once-daily 4.4% [20], twice-daily 7.1% [16]), with a higher rate for the NNRTI stratum of the twice-daily group (8.6% [10]) than in any other stratum (once-daily, NNRTI 4.3% [10]; twice-daily, protease inhibitor 5.6% [6]; once-daily, protease inhibitor 4.6% [10]).


CONCLUSIONS
In the short-term, the rates of adverse events in the once-daily and twice-daily groups appeared to be similar. The rate of suspected abacavir hypersensitivity reaction in the once-daily group was lower than the rate in the twice-daily group.
Cohen
Calvin J
CJ
Community Research Initiative, New England and Harvard Vanguard Medical Associates, Boston, Massachusetts, USA.
Kubota
Marshall
M
Brachman
Philip S
PS
Harley
William B
WB
Schneider
Stefan
S
Williams
Vanessa C
VC
Sutherland-Phillips
Denise H
DH
Lim
Michael L
ML
Balu
Rukmini B
RB
Shaefer
Mark S
MS
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D017060:Patient Satisfaction; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir