BACKGROUND: Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes. METHODS: In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences. RESULTS: Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes. CONCLUSIONS:Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count. CLINICAL TRIALS REGISTRATION: NCT00118898.
RCT Entities:
BACKGROUND: Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes. METHODS: In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infectedparticipants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences. RESULTS: Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes. CONCLUSIONS:Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count. CLINICAL TRIALS REGISTRATION: NCT00118898.
Authors: Lisa L Ross; Winkler G Weinberg; Edwin DeJesus; Margaret A Fischl; Joseph H Horton; Keith A Pappa; C Tracey Lancaster; Gary E Pakes; Kimberly Y Smith Journal: AIDS Res Hum Retroviruses Date: 2010-04 Impact factor: 2.205
Authors: Sung Yong Park; Tanzy M T Love; Jeremy Nelson; Sally W Thurston; Alan S Perelson; Ha Youn Lee Journal: AIDS Date: 2011-10-23 Impact factor: 4.177
Authors: Paul E Sax; Camlin Tierney; Ann C Collier; Margaret A Fischl; Katie Mollan; Lynne Peeples; Catherine Godfrey; Nasreen C Jahed; Laurie Myers; David Katzenstein; Awny Farajallah; James F Rooney; Belinda Ha; William C Woodward; Susan L Koletar; Victoria A Johnson; P Jan Geiseler; Eric S Daar Journal: N Engl J Med Date: 2009-12-01 Impact factor: 91.245
Authors: Steven G Deeks; Stephen J Gange; Mari M Kitahata; Michael S Saag; Amy C Justice; Robert S Hogg; Joseph J Eron; John T Brooks; Sean B Rourke; M John Gill; Ronald J Bosch; Constance A Benson; Ann C Collier; Jeffrey N Martin; Marina B Klein; Lisa P Jacobson; Benigno Rodriguez; Timothy R Sterling; Gregory D Kirk; Sonia Napravnik; Anita R Rachlis; Liviana M Calzavara; Michael A Horberg; Michael J Silverberg; Kelly A Gebo; Margot B Kushel; James J Goedert; Rosemary G McKaig; Richard D Moore Journal: Clin Infect Dis Date: 2009-11-15 Impact factor: 9.079
Authors: M A Winters; K L Coolley; Y A Girard; D J Levee; H Hamdan; R W Shafer; D A Katzenstein; T C Merigan Journal: J Clin Invest Date: 1998-11-15 Impact factor: 14.808
Authors: Robert S Hogg; David R Bangsberg; Viviane D Lima; Chris Alexander; Simon Bonner; Benita Yip; Evan Wood; Winnie W Y Dong; Julio S G Montaner; P Richard Harrigan Journal: PLoS Med Date: 2006-09 Impact factor: 11.069
Authors: Cindy J Bednasz; Charles S Venuto; Qing Ma; Eric S Daar; Paul E Sax; Margaret A Fischl; Ann C Collier; Kimberly Y Smith; Camlin Tierney; Yang Yang; Gregory E Wilding; Gene D Morse Journal: Ther Drug Monit Date: 2017-12 Impact factor: 3.681
Authors: Soo-Yon Rhee; Jose Luis Blanco; Michael R Jordan; Jonathan Taylor; Philippe Lemey; Vici Varghese; Raph L Hamers; Silvia Bertagnolio; Tobias F Rinke de Wit; Avelin F Aghokeng; Jan Albert; Radko Avi; Santiago Avila-Rios; Pascal O Bessong; James I Brooks; Charles A B Boucher; Zabrina L Brumme; Michael P Busch; Hermann Bussmann; Marie-Laure Chaix; Bum Sik Chin; Toni T D'Aquin; Cillian F De Gascun; Anne Derache; Diane Descamps; Alaka K Deshpande; Cyrille F Djoko; Susan H Eshleman; Herve Fleury; Pierre Frange; Seiichiro Fujisaki; P Richard Harrigan; Junko Hattori; Africa Holguin; Gillian M Hunt; Hiroshi Ichimura; Pontiano Kaleebu; David Katzenstein; Sasisopin Kiertiburanakul; Jerome H Kim; Sung Soon Kim; Yanpeng Li; Irja Lutsar; Lynn Morris; Nicaise Ndembi; Kee Peng Ng; Ramesh S Paranjape; Martine Peeters; Mario Poljak; Matt A Price; Manon L Ragonnet-Cronin; Gustavo Reyes-Terán; Morgane Rolland; Sunee Sirivichayakul; Davey M Smith; Marcelo A Soares; Vincent V Soriano; Deogratius Ssemwanga; Maja Stanojevic; Mariane A Stefani; Wataru Sugiura; Somnuek Sungkanuparph; Amilcar Tanuri; Kok Keng Tee; Hong-Ha M Truong; David A M C van de Vijver; Nicole Vidal; Chunfu Yang; Rongge Yang; Gonzalo Yebra; John P A Ioannidis; Anne-Mieke Vandamme; Robert W Shafer Journal: PLoS Med Date: 2015-04-07 Impact factor: 11.069
Authors: Soo-Yon Rhee; Michael R Jordan; Elliot Raizes; Arlene Chua; Neil Parkin; Rami Kantor; Gert U Van Zyl; Irene Mukui; Mina C Hosseinipour; Lisa M Frenkel; Nicaise Ndembi; Raph L Hamers; Tobias F Rinke de Wit; Carole L Wallis; Ravindra K Gupta; Joseph Fokam; Clement Zeh; Jonathan M Schapiro; Sergio Carmona; David Katzenstein; Michele Tang; Avelin F Aghokeng; Tulio De Oliveira; Annemarie M J Wensing; Joel E Gallant; Mark A Wainberg; Douglas D Richman; Joseph E Fitzgibbon; Marco Schito; Silvia Bertagnolio; Chunfu Yang; Robert W Shafer Journal: PLoS One Date: 2015-12-30 Impact factor: 3.240
Authors: Saran Vardhanabhuti; David Katzenstein; John Bartlett; Nagalingeswaran Kumarasamy; Carole L Wallis Journal: Open Forum Infect Dis Date: 2016-08-24 Impact factor: 3.835
Authors: Justen Manasa; Vici Varghese; Sergei L Kosakovsky Pond; Soo-Yon Rhee; Philip L Tzou; W Jeffrey Fessel; Karen S Jang; Elizabeth White; Thorsteinn Rögnvaldsson; David A Katzenstein; Robert W Shafer Journal: Sci Rep Date: 2017-09-14 Impact factor: 4.379