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
1Community Research Initiative, New England and Harvard Vanguard Medical Associates, Boston, Massachusetts.
Marshall Kubota, M.D.2,
2Clinical Services, Department of Health Services, and Sonoma County Department of Family and Community Medicine, University of California, San Francisco, California.
Philip S. Brachman, M.D.3,
3Department of Medicine, Emory University School of Medicine, and Piedmont Hospital, Atlanta, Georgia.
William B. Harley, M.D.4,
4ID Associates, Gastonia, North Carolina.
Stefan Schneider, M.D.5,
5St. Mary Medical Center Care Clinic, Long Beach, California.
Vanessa C. Williams, M.S.6,
6Infectious Diseases Medical Development Center, GlaxoSmithKline, Research Triangle Park, North Carolina.
Denise H. Sutherland-Phillips, M.D.7,
7Infectious Diseases Medical Development Center, GlaxoSmithKline, Research Triangle Park, North Carolina.
Michael L. Lim, Pharm.D.8,
8HIV Centre of Excellence, GlaxoSmithKline, London, United Kingdom.
Rukmini B. Balu, Ph.D.9,
9Infectious Diseases Medical Development Center, GlaxoSmithKline, Research Triangle Park, North Carolina.
for the Abacavir-Lamivudine Once-Daily HIV Assessment (ALOHA) Study GroupMark S. Shaefer, Pharm.D.10*
10Infectious Diseases Medical Development Center, GlaxoSmithKline, Research Triangle Park, North Carolina.
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.
Design. Phase IIIB, randomized, open-label, parallel-group, multicenter study.
Setting. One hundred forty-six human immunodeficiency virus (HIV) clinics.
Patients. Six hundred eighty antiretroviral therapy–naïve patients with HIV type 1 RNA greater than 1000 copies/ml at baseline.
Intervention. 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.
Measurements and Main 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]).
Conclusion. 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.