108LB
A Prospective, Open-label, Pilot Trial of Regimen Simplification to Atazanavir/Ritonavir Alone as Maintenance Antiretroviral Therapy after Sustained Virologic Suppression (ACTG 5201)
Susan Swindells*1, T Wilkin2, G DiRienzo3, C Fletcher4, G Thal5, H Huang3, E Werner4, J McKinnon6, J Mellors6, and the AIDS Clin Trials Group
1Univ of Nebraska Med Ctr, Omaha, US; 2Weill Med Coll, Cornell Univ, New York, NY, US; 3Statistical and Data Analysis Ctr, Harvard Sch of Publ Hlth, Boston, MA, US; 4Univ of Colorado Hlth Sci Ctr, Denver, CO, US; 5Bristol-Myers Squibb, Plainsboro, NJ, US; and 6Univ of Pittsburgh Sch of Med, PA, US
Background: The long-term adverse effects, expense, and
difficulty of adherence to current ART regimens have led to studies of
simplified maintenance therapy. Ritonavir-boosted atazanavir (ATV/RTV) alone is
attractive as maintenance therapy because of its reduced pill burden, once
daily dosing, safety, and unique resistance profile.
Methods: Subjects with virologic suppression for at
least 48 weeks on their first protease inhibitor (PI)-based regimen containing
2 nucleoside reverse transcriptase inhibitors (NRTI) were enrolled into this single-arm,
open-label, multicenter, pilot study. Participants switched from current PI to ATV/RTV at
entry and discontinued NRTI after 6 weeks. The primary study endpoint was
virologic failure (confirmed plasma HIV-1 RNA ≥200 copies/mL) 24 weeks
after stopping NRTI (simplification). A 90% one-sided confidence interval (CI) for
the probability of virologic success (i.e., no virologic failure) 24 weeks
after simplification was calculated using Greenwood’s
variance. Plasma samples at virologic failure were tested for drug resistance
(ViroSeq). Plasma ATV concentrations were measured (HPLC) serially throughout
the study.
Results: We enrolled 36 subjects of whom 2
discontinued before simplification to ATV/RTV alone (1 withdrew consent; 1 HIV
RNA of 50 copies/mL). The median follow-up after simplification was 194 days
(range 84 to 345). There were no treatment discontinuations for adverse events
after simplification. The observed virologic success 24 weeks after
simplification was 91% (lower 90% CI limit = 85%). Of 34 subjects, 3
experienced virologic failure at 12, 14, and 20 weeks after simplification,
with plasma HIV-1 RNA of 1285, 4730, and 28,397 copies/mL, respectively.
Genotyping of plasma samples from the 3 subjects experiencing virologic failure
did not identify any PI mutations. ATV could not be detected in plasma samples
from 2 of 3 subjects at virologic failure. The third had measurable ATV at each
visit and re-suppressed to <50 copies/mL on ATV/RTV alone.
Conclusions: Simplified maintenance therapy with
ATV/RTV alone appears safe and effective through 24 weeks. Virologic failure
occurred in 3 of 34 subjects, 2 of whom had undetectable plasma ATV
concentrations. Resistance to PI was not detected at virologic failure. Larger,
randomized trials are now warranted to define further the efficacy of this
strategy.
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