A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study)

Abstract

BackgroundTraditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities, women of child-bearing potential, and intolerability to components of standard first line therapy. This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient populations. The ACTION study was a randomized, open-label, multicenter, 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects.Results279 HIV-infected subjects with HIV-1 RNA (VL) >5000 but < 200,000 copies/mL (c/mL) and CD4+ count ≥ 100 cells/mm3 were randomized (1:1) to receive abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV) twice-daily or atazanavir (ATV) once-daily plus lamivudine/zidovudine (3TC/ZDV) twice-daily. Protocol-defined virologic failure was based on multiple failure criteria.Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62% vs. 59% of subjects achieving a VL < 50 c/mL at week 48, [ITT(E), M/S = F, 95% CI: -5.9, 10.4]. Similar results were observed in the 230 (82%) subjects with baseline VL<100,000 c/mL (ABC/3TC/ZDV vs. ATV+3TC/ZDV), 66% vs. 59%; 95% CI: -5.6, 19.5. However, ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL ≥ 100,000 c/mL, 39% vs. 60%; 95% CI: -49.2, 7.4, respectively. Protocol-defined virologic failure was similar between groups.ConclusionABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL ≥ 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects.Trial Registration[Clinical Trials Identifier, NCT00082394].

Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana

“…The high rate of suppression in our study was in accord with the results of studies comparing the abacavir–zidovudine–lamivudine with unboosted protease-inhibitor–based HAART 14,15. Unlike some previous studies,14,16 treatment with abacavir–zidovudine–lamivudine was as effective as other HAART regimens when the baseline HIV-1 RNA level was more than 100,000 copies per milliliter. Rates of suppression with nevirapine-based HAART in the observational group were also high, despite more advanced disease and more toxic effects requiring treatment modification among women in this group.…”

Poor Early Virologic Performance and Durability of Abacavir-based First-line Regimens for HIV-infected Children

“…Other adult studies have found suboptimal performance of an ABC-containing triple NRTI regimen at higher pre-treatment VL levels when compared to AZT/3TC and a PI. 20,21 …”

Co-formulated abacavir-lamivudine-zidovudine for initial treatment of HIV infection and AIDS

“…A er scanning the titles and abstracts of all material obtained from the searches conducted from February 2008 to July 2011 (Table 1; Table 2; Table 3; Table 4; Table 5; Table 6; Table 7; Table 8; Cahn 2004;d'Ettorre 2009;Feinberg 2003;Matheron 2003;Munderi 2010;Ndembi 2010;Shao 2009;Sprenger 2010;Staszewski 2001;Vibhagool 2004) and four met our inclusion criteria (Gulick 2004;Kumar 2006;Kumar 2009;Shapiro 2010…”

“…Three trials did not provide an adequate description of the methods used for generating the allocation sequence, but all were described as randomised [Gulick 2004;Kumar 2006;Kumar 2009]. However, the equal allocation of participants suggests that a computergenerated block randomisation process was used.…”