Abacavir (ABC, Ziagen) has been available for the treatment of HIV infection since 1998. When it was originally released the recommended dose was 300 mg taken twice daily. Additional studies, however, demonstrated that it worked just as well when given in a dose of 600 mg once daily.¹

Since abacavir is frequently prescribed together with lamivudine (3TC, Epivir), it made sense to combine them in a fixed-dose tablet in order to simplify therapy for patients. This co-formulated agent, abacavir/lamivudine (ABC/3TC, Epzicom), was recently approved by the U.S. Food and Drug Administration for HIV treatment. This current study is one of a number of trials utilizing abacavir/lamivudine to help us better understand the performance characteristics and potential role of this agent in the management of HIV.

Study

This was a randomized, open-label comparison between the fixed-dose drug combination (FDC) abacavir/lamivudine versus twice-daily abacavir in antiretroviral-experienced subjects. In order to qualify for this study, patients had to have a viral load over 1,000 copies and a CD4+ cell count over 50 cells/mm³. In addition to the randomized abacavir/lamivudine treatment, both groups received tenofovir (TDF, Viread) and either a new protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI) to complete the regimen. This poster detailed the 24-week interim results of this trial.

One hundred eighty-two subjects were randomized: 94 to abacavir/lamivudine and 88 to abacavir twice daily. They were well matched and there were no significant differences in baseline characteristics between the 2 groups. The median viral load and CD4+ cell count were 3.92 log and 309 cells/mm³ in the abacavir/lamivudine group and 4.22 log and 304 cells/mm³ in the abacavir twice-daily group, respectively.

The median HIV-RNA log change (AAUCMB) for the abacavir/lamivudine group was 1.60 versus 1.87 for the twice-daily abacavir group; these changes were not statistically different between the 2 arms. There were also no statistical differences between the number of subjects who achieved a viral load under 50 copies at 24 weeks -- 57% with abacavir/lamivudine and 48% with abacavir twice daily. And finally, no differences in the rate of virologic failure were seen either; 16% with abacavir/lamivudine and 15% with abacavir twice daily.

In terms of side effects, similar numbers of subjects in both arms experienced drug-related adverse effects, mostly gastrointestinal in nature. Numerically more patients (9%) had hypersensitivity reaction on abacavir/lamivudine versus 4% with abacavir twice daily, but this did not reach statistical significance.

Comment

This interim study indicates that abacavir/lamivudine taken once daily was non-inferior to twice-daily abacavir as part of a salvage regimen in treatment-experienced subjects.

There were no surprises here -- this study simply builds upon previous work that abacavir can be used once daily for treatment of HIV infection without any discernible reduction in antiretroviral efficacy or increase in side effects. Further, this study shows that abacavir/lamivudine -- the fixed-dose version of abacavir and lamivudine -- works as expected in antiretroviral-experienced subjects.

Based on this and other studies, it seems logical to use the fixed-dose combination of abacavir/lamivudine instead of abacavir and lamivudine as separate agents. The combination tablet has similar safety and efficacy, lower pill number and one less co-pay for patients with insurance.

Footnote

1. Gazzard BG, DeJesus E, Cahn P, et al. Abacavir (ABC) once daily (OAD) plus lamivudine (3TC) OAD in combination with efavirenz (EFV) OAD is well-tolerated and effective in the treatment of antiretroviral therapy (ART) naive adults with HIV-1 infection (ZODIAC Study: CNA30021). In: Program and abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003; Chicago, Ill. Abstract H-1722b.