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Chemical Compound Review

CHEMBL1380     [(1S)-4-[2-amino-6- (cyclopropylamino)purin...

Synonyms: Abacavir (INN), Abacavir [INN], Bio-0001, SureCN3141966, AC1L9AXG, ...
 
 
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Disease relevance of abacavir

 

Psychiatry related information on abacavir

 

High impact information on abacavir

  • OBJECTIVE: To determine if substitution of stavudine or zidovudine with abacavir improves HIV lipoatrophy without affecting control of HIV replication [1].
  • No proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog that may be less toxic to mitochondria [1].
  • In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%) [7].
  • We aimed to find associations between MHC alleles and abacavir hypersensitivity in HIV-1-positive individuals treated with abacavir [2].
  • Genetic variations in HLA-B region and hypersensitivity reactions to abacavir [8].
 

Chemical compound and disease context of abacavir

 

Biological context of abacavir

 

Anatomical context of abacavir

 

Associations of abacavir with other chemical compounds

 

Gene context of abacavir

 

Analytical, diagnostic and therapeutic context of abacavir

  • PATIENTS AND METHODS: A total of 100 HIV-infected patients with viral load (VL) >500 copies/ml who had a plasma sample available at the time of starting abacavir (baseline) were included [23].
  • Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling [24].
  • CONCLUSIONS: The addition of abacavir during low-level treatment failure may restore or achieve suppression to levels below the cut-off of the ultrasensitive PCR [25].
  • METHODS: Children aged 2-13 years receiving combination treatment containing lamivudine (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included in this single-arm, open-label, crossover study [13].
  • However, the magnitude of resistance observed in cell culture to abacavir in previous studies was less than that observed to other compounds [14].

References

  1. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. Carr, A., Workman, C., Smith, D.E., Hoy, J., Hudson, J., Doong, N., Martin, A., Amin, J., Freund, J., Law, M., Cooper, D.A. JAMA (2002) [Pubmed]
  2. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Mallal, S., Nolan, D., Witt, C., Masel, G., Martin, A.M., Moore, C., Sayer, D., Castley, A., Mamotte, C., Maxwell, D., James, I., Christiansen, F.T. Lancet (2002) [Pubmed]
  3. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Martin, A.M., Nolan, D., Gaudieri, S., Almeida, C.A., Nolan, R., James, I., Carvalho, F., Phillips, E., Christiansen, F.T., Purcell, A.W., McCluskey, J., Mallal, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA. Clumeck, N., Goebel, F., Rozenbaum, W., Gerstoft, J., Staszewski, S., Montaner, J., Johnson, M., Gazzard, B., Stone, C., Athisegaran, R., Moore, S. AIDS (2001) [Pubmed]
  5. HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir. Lanier, E.R., Sturge, G., McClernon, D., Brown, S., Halman, M., Sacktor, N., McArthur, J., Atkinson, J.H., Clifford, D., Price, R.W., Simpson, D., Torres, G., Catalan, J., Marder, K., Power, C., Hall, C., Romero, C., Brew, B. AIDS (2001) [Pubmed]
  6. Human immunodeficiency virus-associated dementia: review of pathogenesis, prophylaxis, and treatment studies of zidovudine therapy. Simpson, D.M. Clin. Infect. Dis. (1999) [Pubmed]
  7. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: A randomized equivalence trial. Staszewski, S., Keiser, P., Montaner, J., Raffi, F., Gathe, J., Brotas, V., Hicks, C., Hammer, S.M., Cooper, D., Johnson, M., Tortell, S., Cutrell, A., Thorborn, D., Isaacs, R., Hetherington, S., Steel, H., Spreen, W. JAMA (2001) [Pubmed]
  8. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Hetherington, S., Hughes, A.R., Mosteller, M., Shortino, D., Baker, K.L., Spreen, W., Lai, E., Davies, K., Handley, A., Dow, D.J., Fling, M.E., Stocum, M., Bowman, C., Thurmond, L.M., Roses, A.D. Lancet (2002) [Pubmed]
  9. Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. Ait-Khaled, M., Rakik, A., Griffin, P., Cutrell, A., Fischl, M.A., Clumeck, N., Greenberg, S.B., Rubio, R., Peters, B.S., Pulido, F., Gould, J., Pearce, G., Spreen, W., Tisdale, M., Lafon, S. Antivir. Ther. (Lond.) (2002) [Pubmed]
  10. HIV-1 reverse transcriptase and protease resistance mutations selected during 16-72 weeks of therapy in isolates from antiretroviral therapy-experienced patients receiving abacavir/efavirenz/amprenavir in the CNA2007 study. Ait-Khaled, M., Rakik, A., Griffin, P., Stone, C., Richards, N., Thomas, D., Falloon, J., Tisdale, M. Antivir. Ther. (Lond.) (2003) [Pubmed]
  11. A dose-ranging study to evaluate the antiretroviral activity and safety of amprenavir alone and in combination with abacavir in HIV-infected adults with limited antiretroviral experience. Schooley, R.T., Clumeck, N., Haubrich, R., Thompson, M., Danner, S.A., van Der Ende, M.E., Sereni, D., Antunes, F., Blake, D., Myers, R.E., Tisdale, M., Millard, J., Mustafa, N., Nacci, P. Antivir. Ther. (Lond.) (2001) [Pubmed]
  12. Loss of antiretroviral drug susceptibility at low viral load during early virological failure in treatment-experienced patients. Parkin, N.T., Deeks, S.G., Wrin, M.T., Yap, J., Grant, R.M., Lee, K.H., Heeren, D., Hellmanna, N.S., Petropoulos, C.J. AIDS (2000) [Pubmed]
  13. Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir: simplification of combination treatment in HIV-1-infected children (PENTA-13). Bergshoeff, A., Burger, D., Verweij, C., Farrelly, L., Flynn, J., Le Prevost, M., Walker, S., Novelli, V., Lyall, H., Khoo, S., Gibb, D. Antivir. Ther. (Lond.) (2005) [Pubmed]
  14. Mechanistic studies to understand the progressive development of resistance in human immunodeficiency virus type 1 reverse transcriptase to abacavir. Ray, A.S., Basavapathruni, A., Anderson, K.S. J. Biol. Chem. (2002) [Pubmed]
  15. 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity. Daluge, S.M., Good, S.S., Faletto, M.B., Miller, W.H., St Clair, M.H., Boone, L.R., Tisdale, M., Parry, N.R., Reardon, J.E., Dornsife, R.E., Averett, D.R., Krenitsky, T.A. Antimicrob. Agents Chemother. (1997) [Pubmed]
  16. Membrane permeation characteristics of abacavir in human erythrocytes and human T-lymphoblastoid CD4+ CEM cells: comparison with (-)-carbovir. Mahony, W.B., Domin, B.A., Daluge, S.M., Zimmerman, T.P. Biochem. Pharmacol. (2004) [Pubmed]
  17. The antiviral activity, mechanism of action, clinical significance and resistance of abacavir in the treatment of pediatric AIDS. Melroy, J., Nair, V. Curr. Pharm. Des. (2005) [Pubmed]
  18. Simplification of protease inhibitor-containing regimens with efavirenz, nevirapine or abacavir: safety and efficacy outcomes. Chiesa, E., Bini, T., Adorni, F., Capetti, A., Rizzardini, G., Faggion, I., Mussini, C., Sollima, S., Melzi, S., Bongiovanni, M., Tordato, F., Cicconi, P., Castelnuovo, B., Rusconi, S., d'Arminio Monforte, A. Antivir. Ther. (Lond.) (2003) [Pubmed]
  19. Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine. McComsey, G.A., Paulsen, D.M., Lonergan, J.T., Hessenthaler, S.M., Hoppel, C.L., Williams, V.C., Fisher, R.L., Cherry, C.L., White-Owen, C., Thompson, K.A., Ross, S.T., Hernandez, J.E., Ross, L.L. AIDS (2005) [Pubmed]
  20. Indinavir, efavirenz, and abacavir pharmacokinetics in human immunodeficiency virus-infected subjects. DiCenzo, R., Forrest, A., Squires, K.E., Hammer, S.M., Fischl, M.A., Wu, H., Cha, R., Morse, G.D. Antimicrob. Agents Chemother. (2003) [Pubmed]
  21. Nucleoside analog 1592U89 and human immunodeficiency virus protease inhibitor 141W94 are synergistic in vitro. Drusano, G.L., D'Argenio, D.Z., Symonds, W., Bilello, P.A., McDowell, J., Sadler, B., Bye, A., Bilello, J.A. Antimicrob. Agents Chemother. (1998) [Pubmed]
  22. Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase. Lederman, M.M., McKinnis, R., Kelleher, D., Cutrell, A., Mellors, J., Neisler, M., Cooney, E., Haas, D.W., Haubrich, R., Stanford, J., Horton, J., Landay, A., Spreen, W. AIDS (2000) [Pubmed]
  23. Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSIDA study. Cabrera, C., Cozzi-Lepri, A., Phillips, A.N., Loveday, C., Kirk, O., Ait-Khaled, M., Reiss, P., Kjaer, J., Ledergerber, B., Lundgren, J.D., Clotet, B., Ruiz, L. Antivir. Ther. (Lond.) (2004) [Pubmed]
  24. Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. Maggiolo, F., Callegaro, A., Arici, C., Quinzan, G., Gregis, G., Ripamonti, D., Tebaldi, A., Goglio, A., Suter, F. Antivir. Ther. (Lond.) (2003) [Pubmed]
  25. Intensification of background antiretroviral therapy with abacavir during low-level failure may restore optimal suppression. Degen, O., van Lunzen, J., Stellbrink, H.J. Antivir. Ther. (Lond.) (2000) [Pubmed]
 
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