Abacavir Once or Twice Daily Combined With Once-Daily Lamivudine and Efavirenz for the Treatment of Antiretroviral-Naive HIV-Infected Adults

Abstract

The long intracellular half-life of abacavir (ABC) supports its once-daily use, and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen. A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily (n = 384) versus 300 mg of ABC administered twice daily (n = 386) in combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL (44% with viral load >100,000 copies/mL), and the median CD4 cell count was 262 cells/mm. ABC administered once daily was non-inferior to the twice-daily regimen, with 66% and 68% of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level <50 copies/mL (95% confidence interval: -8.4%, 4.9%). The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure (10% vs. 8%), emergence of resistance mutations, CD4 cell increases from baseline (median, 188 vs. 200 cells/mm), safety profile, and incidence of ABC-related hypersensitivity reactions (9% vs. 7%). ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks.

Switching from twice‐daily abacavir and lamivudine to the once‐daily fixed‐dose combination tablet of abacavir and lamivudine improves patient adherence and satisfaction with therapy

“…These half-lives not only suggest reasonable forgiveness but are similar to other qd-dosed antiretrovirals such as NVP and atazanavir or atazanavir/ ritonavir (although they are somewhat shorter than for EFV). Data for the ZODIAC study indicate that there is no efficacy or safety advantage in initiating ABC bid relative to ABC qd with 3TC and EFV qd [11], an observation reinforced by ours and other studies involving this combination [21]. The absence of a drug interaction between ABC or 3TC and atazanavir makes the ABC-3TC combined tablet an attractive option if this protease inhibitor is used as part of a qd regimen.…”

Point Mutations Associated with HIV-1 Drug Resistance, Evasion of the Immune Response and AIDS Pathogenesis

“…For instance, the presence of K65R or L74V (J. Eron, Jr. et al, 2006;Gallant et al, 2006;Moyle et al, 2005) point mutations ( Figure 2 and Table 2) in addition to the M184V is sufficient for high level resistance to ddI and ABC , particularly in patients with non-subtype B clades (Harrigan et al, 2000;Lanier et al, 2004a;Svarovskaia et al, 2007;M. A. Winters et al, 1997 .…”

“…However, several patients harbouring HIV-1 species containing the L74V point mutation while receiving a regimen containing ABC or ddI have been found to have minor variants containing K65R (Descamps et al, 2006;Svarovskaia et al, 2007). On the other hand, K65R and M184V mutations are primarily found in patients receiving the NRTI backbone TDF/3TC (Gallant et al, 2004;Margot et al, 2006) and less commonly ABC/3TC (Moyle et al, 2005) or TDF/FTC (Gallant et al, 2006;Smith et al, 2008). L74V and M184V mutations primarily occur in patients receiving ABC/3TC or ddI/3TC/FTC NRTI backbones (Descamps et al, 2006;Moyle et al, 2005;Sosa et al, 2005).…”

“…On the other hand, K65R and M184V mutations are primarily found in patients receiving the NRTI backbone TDF/3TC (Gallant et al, 2004;Margot et al, 2006) and less commonly ABC/3TC (Moyle et al, 2005) or TDF/FTC (Gallant et al, 2006;Smith et al, 2008). L74V and M184V mutations primarily occur in patients receiving ABC/3TC or ddI/3TC/FTC NRTI backbones (Descamps et al, 2006;Moyle et al, 2005;Sosa et al, 2005). In addition to the M184V, K65R and L74V mutations, which between them cause resistance to ABC, 3TC, FTC, TDF and ddI by the exclusion mechanism; there is a complex set of several mutations that involves Q151M causing multi-NRTI resistant ( Figure 2 and Table 2).…”

Abacavir/lamivudine combination in the treatment of HIV: a review

“…The ZODIAC study 51 evaluated the efficacy and safety of once daily versus twice daily doses of ABC. This was a randomized double-blind study.…”