Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes
Timothy J Wilkin, John E McKinnon, A Gregory DiRienzo, Katie Mollan, Courtney V Fletcher, David M Margolis, Barbara Bastow, Gary Thal, William Woodward, Catherine Godfrey, Ann Wiegand, Frank Maldarelli, Sarah Palmer, John M Coffin, John W Mellors, Susan Swindells, Timothy J Wilkin, John E McKinnon, A Gregory DiRienzo, Katie Mollan, Courtney V Fletcher, David M Margolis, Barbara Bastow, Gary Thal, William Woodward, Catherine Godfrey, Ann Wiegand, Frank Maldarelli, Sarah Palmer, John M Coffin, John W Mellors, Susan Swindells
Abstract
Background: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)-sparing benefits, low pill burden, once-daily dosage, and safety.
Methods: Subjects with virologic suppression after > or = 48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level > or = 200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1-49 copies/mL) was measured by single-copy assay.
Results: Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88%) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4-12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS.
Conclusions: In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy.
Trial registration: ClinicalTrials.gov NCT00084019.
Conflict of interest statement
Potential conflicts of interest: T.J.W. has received research support from Tibotec and has served as an ad-hoc advisor for Tibotec and Pfizer. J.E.M. was a recipient of a Bristol-Myers Squibb (BMS) Virology Fellows Research Program award. C.V.F. has participated in ad-hoc advisory boards for Abbott Pharmaceuticals, BMS, GlaxoSmith-Kline (GSK), and Roche. D.M.M. has received honoraria or research support from BMS, GSK, Abbott, Merck, Tibotec, Virco, Roche, and Trimeris. G.T. is an employee of BMS and owns stock in the company. W.W. is an employee of Abbott Laboratories and owns stock options in the company. J.W.M. has been a consultant to Abbott Laboratories, BMS, Agouron Pharmaceuticals, Boehringer Ingelheim, Gilead Sciences, GSK, Intelligent Therapeutic Solutions, Merck, Noviro/Idenix, Pfizer, Pharmasset, Trimeris, and Visible Genetics; has owned or currently owns stock or stock options in Achillion Pharmaceuticals, Novirio/Idenix, Intelligent Therapeutic Solutions, Pharmasset, Triangle Pharmaceuticals, and Virco-Tibotec; and has filed the following patent: US patent application PCT/US07/02369, 2007 (“HIV-1 Mutations at Codon 371 and 509 of Reverse Transcriptase Increase Resistance to Nucleoside Analogs Such as 3′-Azidothymidine”). S.S. has received research grants or contracts from or was a consultant for Abbott Pharmaceuticals, BMS, Novartis Pharmaceuticals, Tibotec Therapeutics, Pfizer, and Bavarian Nordic. All other authors report no potential conflicts.
Source: PubMed