Over the past few years, many studies have provided compelling data on the effectiveness of once-a-day regimens in antiretroviral treatment-naive patients. With the availability of many antiretroviral drugs with pharmocogenetic profiles favoring once-daily administration, it is not surprising to see more than 16 potential once-daily combinations useful for HIV-infected patients.

The TEDAL study is a prospective, randomized multicenter open-label study looking at the efficacy of efavirenz (EFV, Sustiva, Stocrin) with 3 different once-daily regimens in treatment-naive patients in Italy. The study, which is scheduled to continue for a full year, had interim 6-month analysis presented at this conference.

Franco Maggiolo presented the data on 199 treatment-naive patients who were randomized to receive efavirenz combined with a once-daily backbone regimen consisting of either:

• lamivudine (3TC, Epivir) + didanosine (ddI, Videx) (n=72), or

• lamivudine + tenofovir (TDF, Viread) (N=64), or

• didanosine + abacavir (ABC, Ziagen) (N=63).

Trial participants' baseline characteristics -- in terms of age, sex, viral load and CD4+ cell count -- were similar in each of the 3 arms. Patients' mean baseline CD4+ cell count was ~200 cells/mm³ and the mean baseline viral load was ~200,000 copies/mL.

At 24 weeks, the rate of discontinuation was 11% in the lamivudine + didanosine group, versus 10% in the lamivudine + tenofovir group versus 18% in the didanosine + abacavir group; so more patients discontinued on the didanosine + abacavir arm. The proportion of patients with an HIV-RNA below 50 copies/mL on an intent-to-treat analysis was 70% in lamivudine + didanosine arm, versus 61% in the lamivudine + tenofovir arm versus 62% in the didanosine + abacavir arm. CD4+ cell count reconstitution was fairly equal across all treatment arms with a ~350 cell gain.

For the most part, in this preliminary analysis, all 3 of these regimens are effective and safe, despite the trend of more discontinuations and a slightly higher rate of virologic failure in the didanosine + abacavir once-daily arm. Patients also reported a mean adherence rate of ~95% in all treatment arms.

The main difference observed in this study between these regimens was in the resistance patterns observed on those regimens, which was highly influenced by the NRTI backbone used.

In terms of resistance, at baseline, most patients had no significant reverse transcriptase mutations. Of the 22 patients with virologic failure: L74V was the most common mutation observed, in 12 patients (8 in the didanosine + abacavir arm, 2 in the lamivudine + didanosine arm and 2 in the lamivudine + tenofovir arm). Seven patients developed K65R (4 in the lamivudine + tenofovir arm and 3 in the didanosine + abacavir arm). On the other hand, 184V was more frequently selected in the lamivudine + didanosine arm (in 5 out 8 participants).

This is a preliminary 24-week analysis. It is possible that the 48-week results will continue to demonstrate similar results or intensify the initial trends already apparent.

In my opinion, although it appears that all 3 regimens are similar in efficacy and safety, the trend toward more virologic failure and discontinuations on the didanosine + abacavir arm, in addition to the emergence of more reverse transcriptase mutations, potentially make the didanosine + abacavir regimen less attractive. This regimen also contains drugs that can select for similar point reverse transcriptase mutations. In addition, there is an additional inconvenience of pill burden (since abacavir is not currently available as a single pill daily), and there is also the potential for food interference because didanosine should be administered on an empty stomach.