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Role of atazanavir in the treatment of HIV infection

By Pablo Rivas, Judit Morello, Carolina Garrido, Sonia Rodríguez-Nóvoa and Vincent Soriano


Atazanavir (ATV) is one of the latest protease inhibitors (PI) approved for the treatment of HIV infection. The drug has a relatively long-life (~7 h) and large inhibitory quotient which allows once daily administration. It is generally well tolerated and the main side effect is hyperbilirubinemia, since ATV inhibits the hepatic uridin-glucoronyl-transferase. A signature mutation at the protease gene, I50L, may confer loss of susceptibility to the drug. Interestingly, it produces hypersusceptibility to all other PIs. When ATV is pharmacokinetically boosted with ritonavir (r) 100 mg/day, a greater genetic barrier for resistance is achieved, and generally more than 3 major PI resistance associated mutations are needed to result in ATV resistance. In drug-naïve subjects, regimens based on ATV/r have shown non-inferiority compared to lopinavir (LPV)/r (CASTLE study) or fosamprenavir/r (ALERT trial), generally with improved tolerance (less diarrhea and dyslipidemia). Given its good tolerance and convenience, ATV has been proven to be successful as a simplification strategy in switch studies (ie, SWAN and SLOAT) conducted in patients with complete virological suppression under other PI-based regimens. Finally, ATV/r-based combinations have shown to be equivalent in terms of viral response to other PI/r-containing regimens, including LPV/r, in rescue interventions in patients failing other PI regimens (ie, studies AI424-045 and NADIS)

Topics: Review
Publisher: Dove Medical Press
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Provided by: PubMed Central

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  1. 96-week comparison of once-daily Atazanavir/ritonavir and twice-daily Lopinavir/ ritonavir in patients with multiple virologic failures.
  2. A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIVpositive patients.
  3. (2005). AI424067: Improvement in lipid profi les after 12 weeks of switching to atazanavir from boosted or unboosted protease inhibitors in patients with no previous PI virologic failure and hyperlipidemia at baseline.
  4. (2008). Antiretroviral treatment of adult HIV infection:
  5. Antiviral activity and clinical effi cacy of atazanavir in HIV-1-infected patients: A review.
  6. (2005). Atazanavir Ctrough is associated with effi cacy and safety at 24 weeks: Defi nition of therapeutic range.
  7. Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen.
  8. (2008). Atazanavir in patients with persistent viral replication despite HAART: Results from the French prospective NADIS cohort. HIV Clin Trials.
  9. (2005). Atazanavir inhibits P-glycoprotein and multidrug resistanceassociated protein effl ux activity. J Acquir Immune Defi c Syndr.
  10. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures.
  11. Atazanavir urolithiasis.
  12. (2005). Atazanavir: Effects on P-glycoprotein transport and CYP3A metabolism in vitro. Drug Metab Dispos.
  13. (2008). Atazanavir/ritonavir: A review of its use in HIV therapy. Drugs Today (Barc).
  14. (2006). Body fat and other metabolic effects of atazanavir and EFV, each administered in combination with ZDV plus lamivudine, in antiretroviral-naive HIV-infected patients. Clin Infect Dis.
  15. Cardiovascular risk score change in HIV-1-infected patients switched to an atazanavir-based combination antiretroviral regimen.
  16. (2007). Changing rates and patterns of drug resistance mutations in antiretroviral-experienced HIV-infected patients. AIDS Res Hum Retroviruses.
  17. (2006). Clinical pharmacodynamics of HIV-1 protease inhibitors: Use of inhibitory quotients to optimise pharmacotherapy. Lancet Infect Dis.
  18. Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitorexperienced patients.
  19. (2008). Company. Clinical Study Report AI424067.
  20. (2005). Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: A randomized multinational trial. Curr Med Res Opin.
  21. (2004). Comparison of once-daily atazanavir with efavirenz, each in combination with fi xed-dose ZDV and lamivudine, as initial therapy for patients infected with HIV. J Acquir Immune Defi c Syndr.
  22. (2008). Continuation of BID boosted PI vs switch to once-daily ATV/RTV for the management of lipodystrophy: 48 week primary analysis of the 96 week multicenter, open-label, randomized, prospective ReAL study.
  23. Different patterns of mutations involved in the genotypic resistance score for atazanavir boosted versus atazanavir unboosted in multiply failing patients. Antivir Ther. 2006;11 suppl 1:S99.
  24. (2007). Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defi c Syndr.
  25. Effect of atazanavir versus other protease inhibitor-containing antiretroviral therapy on endothelial function in HIV-infected persons: Randomized controlled trial. Heart
  26. Effects of atazanavir/ ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: Demonstrable differences in vitro and clinically.
  27. (2008). Effi cacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients. J Acquir Immune Defi c Syndr.
  28. Effi cacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: Final results of the SLOAT trial.
  29. (2007). Effi cacy and safety of switching from lopinavir/r (LPV/r) to atazanavir/r (ATV/r) in patients with virologic suppression receiving a LPV/r containing HAART:
  30. Electrocardiographic changes in HIV-infected, drug-experienced patients being treated with atazanavir.
  31. for the BMS-AI424138 Study Group. The CASTLE study 48 weeks results: The impact of HIV subtypes and baseline resistance on treatment outcomes and the emergence of resistance. Antivir Ther. 2008;13 suppl 3:A135.
  32. (2008). Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT. AIDS Res Ther.
  33. Frequent co-occurrence of the TATA box mutation associated with Gilbert’s syndrome (UGT1A1*28) with other polymorphisms of the
  34. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.
  35. Genetic factors infl uencing atazanavir plasma concentrations and the risk of severe hyperbilirubinemia.
  36. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia.
  37. Gilbert’s disease and atazanavir: from phenotype to UDP-glucuronosyltransferase haplotype.
  38. Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
  39. HIV-1 drug resistance mutations: An updated framework for the second decade of HAART.
  40. Hollow-fi ber unit evaluation of a new HIV type 1 protease inhibitor, BMS-232632, for determination of the linked pharmacodynamic variable.
  41. Identifi cation of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens.
  42. Improvement in insulin sensitivity and dyslipidemia in protease inhibitor-treated adult male patients after switch to atazanavir/ritonavir.
  43. (2005). In vitro inhibition of UDP glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos.
  44. (2008). Increase in serum bilirubin in HIV/HCV coinfected patients on stable atazanavir therapy following initiation of peginterferon plus ribavirin. AIDS.
  45. Infl uence of liver fi brosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C.
  46. (2004). Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated HIV-infected patients. Antimicrob Agents Chemother.
  47. (2004). Long-term effi cacy and safety of atazanavir with stavudine and lamivudine in patients previously treated with nelfi navir or atazanavir. J Acquir Immune Defi c Syndr.
  48. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV.
  49. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-ofconcept pilot clinical trial (OK study).
  50. (2006). MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype. Clin Pharmacol Ther.
  51. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week effi cacy and safety results of the CASTLE study.
  52. (2008). PEARLS (ACTG A5175): A multinational study of didanosine-EC, emtricitabine and atazanavir vs co-formulated ZDV/lamivudine and EFV for initial treatment of HIV-1 infection.
  53. (2006). Performance of six different ritonavir-boosted protease inhibitor-based regimens in heavily antiretroviral-experienced HIV-infected patients. HIV Clin Trials.
  54. (2004). Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet.
  55. (2006). Plasma levels of atazanavir and the risk of hyperbilirubinemia are predicted by the 3435C – T polymorphism at the multidrug resistance gene 1. Clin Infect Dis.
  56. (2006). Population pharmacokinetics of atazanavir in patients with HIV infection. Antimicrob Agents Chemother.
  57. (2004). Predictors of virological response to atazanavir in protease inhibitor-experienced patients. HIV Clin Trials.
  58. randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results.
  59. Regimen simplifi cation to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression.
  60. Regression of lipodystrophy in HIV-infected patients under therapy with the new protease inhibitor atazanavir.
  61. (2008). Ritonavir-boosted atazanavir, methadone, and ventricular tachycardia: 2 case reports. Clin Infect Dis.
  62. Ritonavir-boosted protease inhibitor monotherapy for the treatment of HIV-1 infection.
  63. Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene.
  64. (1995). Specificity of human UDPglucuronosyltransferases and xenobiotic glucuronidation. Life Sci.
  65. (2008). Squibb Company. Princeton, NJ 08543, USA. Reyataz product information.
  66. Steady state pharmacokinetics and safety of atazanavir after treatment with
  67. (2008). Switch from ritonavirboosted to unboosted atazanavir guided by therapeutic drug monitoring. AIDS Res Hum Retroviruses.
  68. Switching to unboosted atazanavir improves glucose tolerance in highly pretreated HIV-1 infected subjects.
  69. The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts.
  70. The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals.
  71. (2007). The PATCG 1020 protocol: Atazanavir with or without ritonavir in HIV-infected infants, children, and adolescents.
  72. The role of compartment penetration in PI-monotherapy: The atazanavir-ritonavir monomaintenance (ATARITMO) trial.
  73. Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: A randomized comparative pilot trial.
  74. (2008). Update of the drug resistance mutations in HIV-1: Spring
  75. (2006). Updated guidelines to perform therapeutic drug monitoring for antiretroviral agents. Rev Antivir Ther.
  76. (2007). Urolithiasis in HIV-positive patients treated with atazanavir. Clin Infect Dis.
  77. Virological failure and subsequent resistance profiles in individuals exposed to atazanavir.
  78. (2006). Virological responses to atazanavir-ritonavir-based regimens: resistance substitutions score and pharmacokinetic parameters (Reyaphar study). Antivir Ther.

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