TDF/ddI/EFV as initial therapy appears to have diminished efficacy in subjects with CD4 < 200 x 10 cells/l and viral load > 100,000 copies/ml. Treatment failure with resistance was not attributable to baseline resistance, efavirenz exposure or poor adherence.
Patients prefer fewer pills and once-daily (qd) dosing without food restrictions. We assessed the impact on adherence [by Medication Event Monitoring System (MEMS) cap monitoring] of switching from abacavir (ABC) and lamivudine (3TC) twice daily (bid) to ABC/3TC fixed-dose formulation (FDC, Kivexa s ) qd to achieve a qd regimen.
MethodsA randomized, open-label, 8-week study comparing adherence, efficacy and safety of immediate vs. delayed switching from ABC/3TC to FDC qd.
ResultsNinety-four patients were dosed. Significantly improved adherence was observed at week 4 with qd ABC/3TC across all three adherence variables: taking compliance 99.2% (90.7-100%) vs. 96.6% (60.0-100%) (P 5 0.017); dosing compliance 97.1% (64.3-100%) vs. 91.9% (33.3-100%) (P 5 0.016); and timing compliance 95.5% (53.8-100%) vs. 86.3% (4.3-100%) (P 5 0.006). Treatment satisfaction increased significantly at week 4 with ABC/3TC qd [92% (82-99%) vs. 85% (75-93%) (P 5 0.004)]. Two patients were withdrawn from the study because of intolerance to ABC/3TC.
ConclusionsSwitching from ABC and 3TC bid to ABC/3TC FDC qd significantly improved adherence by MEMS cap monitoring at week 4 and improved patient satisfaction with therapy. The results remain to be confirmed over a longer follow-up. Use of qd regimens supports adherence and improves treatment satisfaction relative to bid regimens.Keywords: abacavir, adherence, HIV, lamivudine, once daily, treatment satisfaction
IntroductionSignificant improvements have been observed in HIVassociated mortality and morbidity since the introduction of highly active antiretroviral therapy (HAART) [1]. Therapeutic success with any medication is dependent not only on the intrinsic properties of that medication but also on the individual's ability to reliably take the medication. This is particularly true in HIV infection, where the consequence of failing to achieve durable full viral suppression with antiretroviral therapy (ART) is the evolution of resistant virus and a reduction in treatment options [2]. Factors consistently associated with treatment success include the individual's belief systems regarding medication [3], education regarding HIV disease and its management [4], active substance abuse [5] and the social, emotional and financial status of the individual [6]. Factors relating specifically to ART include medication tolerability [7] and regimen characteristics such as the frequency of dosing and the number of pills per intake [8].A systematic review of studies across a range of medical specialties in which adherence was assessed by electronic recording devices indicated that once-daily (qd) therapy improves adherence to therapy relative to more frequent DOI: 10.1111DOI: 10. /j.1468DOI: 10. -1293DOI: 10. .2008 (2008), 9, 667-672 667 dosing, although statistical significance was not demonstrated relative to twice-daily (bid) regimens [9]. A large survey of HIV-positive persons has indicated that they would prefer therapy involving few pills, qd dosing and no food restrictions [10]. An increasing num...
The mechanism of differential intracellular protease inhibitor accumulation is unclear. Co-administration of atazanavir caused an increase in both the plasma and cellular exposure (AUC0-24) and C24 of saquinavir but not ritonavir.
This review summarizes the current literature regarding the pharmacokinetics of double-boosted protease inhibitor regimens and general considerations regarding their usage in the treatment of HIV-infected patients.
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