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Background:  Once daily regimens may simplify antiretroviral therapy. Study CNA30021was a randomized, double-blind, multicenter, international study to examine the efficacy of ABC once daily vs ABC twice daily.

Methods:  Plasma from subjects with virological failure (failure to achieve plasma HIV-1 RNA <50 copies/mL by week 48 or confirmed value >50 copies/mL after suppression) were assessed to 48 weeks by ViroSeq genotyping and PhenoSense drug susceptibility assay. The analysis was restricted to plasma HIV-1 RNA >500 copies/mL for technical reasons.

Results:  Virologic failure was uncommon (ABC once daily: 38/384 [10%]; ABC twice daily: 32/386 [8%]) and due to low viral load in these failures, only a minority of on-therapy samples could be analysed (ABC once daily: 16/38 [42%]; ABC twice daily: 15/32 [47%]). The frequency of baseline resistance mutations was low, but higher in the ABC once daily arm (number of baseline NRTI and NNRTI resistance associated mutations: ABC once daily: 15 in 7/38 subjects [18%]; ABC twice daily: 4 in 2/32 subjects [6%]). This was also true among subjects in the paired baseline-on-therapy analysis (total number of subjects with baseline resistance mutations: ABC once daily: 5/16 [31%]; ABC twice daily: 2/15 [13%]). High-level resistance to 3TC or EFV (>10-fold) was observed at baseline in 4/16 (25%) ABC once daily subjects and in 1/15 (7%) ABC twice daily subjects. There were no significant differences between arms in the numbers of subjects with treatment-emergent resistance to any study drug (ABC once daily: 13/16; ABC twice daily: 10/15). The most frequent NRTI resistance-associated mutations to emerge during therapy were M184V (ABC once daily: n = 10; ABC twice daily: n = 5), and L74V (ABC once daily: n = 5; ABC twice daily n = 3). Other emergent NRTI resistance-associated mutations were infrequent (K65R:  n = 1, Y115F:  n = 2, thymidine analogue mutations: n = 2) and were observed among subjects with baseline resistance. Treatment-emergent NNRTI-resistance associated mutations were similar in both arms (total EFV-related mutations: ABC once daily: n = 12; ABC twice daily: n = 13; K103N: ABC once daily: n = 6; ABC twice daily n = 8). Drug susceptibility analysis indicated susceptibility was retained to ZDV, d4T, and TDF in all subjects, and to ddI and ABC in 75 to 85% of subjects.

Conclusions:  ABC twice daily or once daily has a similar resistance profile when used in combination with 3TC and EFV.  The frequency of virologic failure was low in both groups of subjects. While additional data are needed, the risk of treatment-emergent resistance or cross-resistance appears to be similar when ABC is administered once daily or twice daily.

Keywords: abacavir; once daily; fixed dose