Fixed-dose Abacavir/3TC Administered Once-daily Compared with Separate Components Twice-daily: The ALOHA Study

Regimen simplification has demonstrated success as a strategy to improve adherence and thus plays a role in successful antiretroviral therapy.

As reported at the 46th ICAAC, held last week in San Francisco, researchers evaluated the short-term safety and tolerability of the fixed-dose combination of 600/300 mg abacavir/3TC (Epzicom/Kivexa) administered once daily versus separate 300 mg abacavir (Ziagen) and 150 mg 3TC (Epivir) tablets administered twice daily as part of a HAART regimen.

This randomized, 12-week, open-label study included 680 antiretroviral-naive HIV positive adults at 146 U.S. sites with HIV RNA levels of at least 1000 copies/mL. Subjects were randomized 2:1 to the once-daily or twice-daily arms abacavir/3TC arms; in addition, all received an investigator-selected third antiretroviral drug.

Most participants (about 85%) were men. About 45% were white, about 35% were black, and about 18% were Hispanic. The median baseline viral load was 4.9 logs and the mean CD4 count was about 225 cells/mm3. In addition to abacavir/3TC, about 50% of the patients also took a NNRTI, about 48% took a protease inhibitor, and 1% took a third NRTI.

Primary endpoints were adverse events and serious adverse events, including abacavir hypersensitivity reactions (HSR). The study did not have the statistical power to compare treatment arms.

Results

81% of the 680 subjects completed the study.

The median decrease in HIV RNA at Week 12 was about 2.65 logs in both arms.

The median increases in CD4 count were 108 cells/mm3 in the once-daily and 124 cells/mm3 in the twice-daily arm.

Grade 2-4 drug-related adverse events occurred in 47 patients (10%) in the once-daily arm and 36 (16%) in the twice-daily arm.

For serious adverse events, the numbers were 21 (5%) and 17 (8%), respectively.

Abacavir hypersensitivity reaction was the most frequently reported Grade 2-4 drug-related event, occurring in 20 (4.4%) and 16 (7.1%) patients in the once-daily and twice-daily arms, respectively.

The median time to HSR onset was 10.5 and 11.5 days, respectively.

HSR was Grade 3 or 4 in 4 patients (0.9%) in the once-daily arm and 5 (2.2%) in the twice-daily arm.

3 patients (0.7%) in the once-daily arm and 1 (0.4%) in the twice-daily arm were hospitalized due to HSR.

Conclusion

The researchers concluded, "The rates of adverse events and serious adverse events do not appear to differ between [once-daily] and [twice-daily] arms in this study."

However, they added, "Fewer suspected hypersensitivity events were reported in the [once-daily arm] (4.4%) than the [twice-daily] arm (7.1%). A lower proportion of HSR events in the [once-daily arm] arm (20%) were Grade 3/4 than in the [twice-daily] arm (31%)."

10/06/06

Reference
M Kubota, C Cohen, A Scribner, and others. Short-term Safety and Tolerability of ABC/3TC Administered Once-Daily (QD) Compared with the Separate Components Administered Twice-Daily (BID): Results From ESS101822 (ALOHA). 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-1904.

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