Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity

Journal of Antimicrobial Chemotherapy

Volumn 65, Issue 11, 2010, Pages 2300-2304

  Fun, Axel ^a   van Baelen, Kurt ^b   van Lelyveld, Steven F L ^a   Schipper, Pauline J ^a   Stuyver, Lieven J ^b   Wensing, Annemarie M J ^a   Nijhuis, Monique ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b Virco BVBA   (Belgium)

Author keywords

Fitness; HIV; Secondary resistance mutation; Treatment interruption

Indexed keywords

DARUNAVIR; ELVITEGRAVIR; EMTRICITABINE; ETRAVIRINE; FOSAMPRENAVIR PLUS RITONAVIR; INTEGRASE; LAMIVUDINE PLUS ZIDOVUDINE; MARAVIROC; RALTEGRAVIR; TENOFOVIR; TIPRANAVIR; VIRUS RNA;

ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CASE REPORT; CD4 LYMPHOCYTE COUNT; DRUG TREATMENT FAILURE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; IN VIVO STUDY; MOLECULAR CLONING; MUTATIONAL ANALYSIS; NONHUMAN; VIRUS GENE; VIRUS LOAD; VIRUS MUTATION; VIRUS RECOMBINANT; VIRUS REPLICATION; VIRUS STRAIN;

AMINO ACID SUBSTITUTION; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DRUG RESISTANCE, VIRAL; EVOLUTION, MOLECULAR; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MUTATION, MISSENSE; SELECTION, GENETIC; TREATMENT FAILURE; VIRAL LOAD; VIRUS REPLICATION;

EID: 77957862994     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkq319     Document Type: Article

References (10)

1. Cooper DA, Steigbigel RT, Gatell JM et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008; 359: 355-65.
2. Steigbigel RT, Cooper DA, Kumar PN et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008; 359: 339-54.
3. Miller MD, Danovich R, Ke Y et al. Longitudinal analysis of resistance to the HIV-1 integrase inhibitor raltegravir: results from P005 a Phase 2 study in treatment experienced patients. Antiviral Ther 2008; 13: A8.
4. Van Baelen K, Van Eygen V, Rondelez E et al. Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility. AIDS 2008; 22: 1877-80.
5. Van Baelen K, Rondelez E, Van Eygen V et al. A combined genotypic and phenotypic human immunodeficiency virus type 1 recombinant virus assay for the reverse transcriptase and integrase genes. J Virol Methods 2009; 161: 231-9.
6. Nakahara K, Wakasa-Morimoto C, Kobayashi M et al. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res 2009; 81: 141-6.
7. Steigbigel RT, Cooper DA, Eron JE et al. 96-week results from BENCHMRK 1&2, Phase III studies of raltegravir (RAL) in patients (pts) failing antiretroviral therapy (ART) with triple-class resistant HIV. In: Abstracts of the Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, Canada, 2009. Abstract 571B. Foundation for Retrovirology and Human Health, Alexandria, VA, USA.
8. Shimura K, Kodama E, Sakagami Y et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol 2008; 82: 764-74.
9. Hatano H, Lampiris H, Huang W et al. Virologic and immunologic outcomes in a cohort of subjects failing integrase inhibitors. Antiviral Ther 2008; 13: A12.
10. Hazuda DJ, Young SD, Guare JP et al. Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques. Science 2004; 305: 528-32.