Pediatric Drugs

, Volume 14, Issue 2, pp 131–141

Atazanavir

In Pediatric Patients with HIV-1 Infection
Adis Drug Profile

Abstract

Atazanavir is a selective and potent inhibitor of the HIV-1 protease. The drug is administered in combination with low-dose ritonavir, to boost atazanavir pharmacokinetics (i.e. ritonavir-boosted atazanavir), and other antiretroviral agents.

The efficacy of once-daily ritonavir-boosted atazanavir plus background therapy (BT) in establishing virologic suppression in treatment-naive pediatric patients (aged 6 to <18 years) infected with HIV-1 was demonstrated in an ongoing, open-label, multi-center, phase I/II trial (PACTG 1020A). HIV-1 RNA levels of <50 or <400 copies/mL were achieved by the majority of patients (>70%) after 24 weeks’ therapy, with these benefits maintained at week 48.

Some treatment-experienced pediatric patients (aged 6 to < 18 years) also achieved HIV-1 RNA levels of <50 or <400 copies/mL in the PACTG 1020A trial after 24 (≤45% of patients) and 48 (≤32%) weeks of treatment with ritonavir-boosted atazanavir plus BT, although the benefits of the regimen in this patient population appeared to be limited by as few as one or two protease inhibitor resistance mutations.

Treatment-experienced pediatric patients (aged 10–19 years) infected with HIV-1 had mixed success in establishing/maintaining virologic suppression when they were switched from their current antiretroviral treatment regimen to once-daily ritonavir-boosted atazanavir plus BT in a small, single-center, observational study. However, some patients may have received atazanavir at a suboptimal dosage or had suboptimal susceptibility to BT agents.

In the PACTG 1020A trial, use of atazanavir (with or without ritonavir) in pediatric patients aged 6 to <18 years was associated with a similar safety profile to that reported in adults.

References

  1. 1.
    World Health Organization. Global summary of the AIDS epidemic, 2009 [online]. Available from URL: http://www.who.int/hiv/data/2009_global_summary.png [Accessed 2001 Oct 14]
  2. 2.
    Patel K, Hernán MA, Williams PL, et al. Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. Clin Infect Dis 2008 Feb 15; 46(4): 507–15PubMedCrossRefGoogle Scholar
  3. 3.
    PENTA Steering Committee, Welch S, Sharland M, et al. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV Med 2009 Nov; 10(10): 591–613PubMedCrossRefGoogle Scholar
  4. 4.
    Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection [online]. Available from URL: http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf [Accessed 2011 Dec 12]
  5. 5.
    Kim RJ, Rutstein RM. Impact of antiretroviral therapy on growth, body composition and metabolism in pediatric HIV patients. Pediatr Drugs 2010 Jun; 12(3): 187–99CrossRefGoogle Scholar
  6. 6.
    Croom KF, Dhillon S, Keam SJ. Atazanavir: a review of its use in the management of HIV-1 infection. Drugs 2009 May 29; 69(8): 1107–40PubMedCrossRefGoogle Scholar
  7. 7.
    Swainston Harrison T, Scott LJ. Atazanavir: a review of its use in the management of HIV infection. Drugs 2005; 65(16): 2309–36PubMedCrossRefGoogle Scholar
  8. 8.
    Bristol-Myers Squibb Company. Reyataz® (atazanavir sulfate) capsules: US prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s025lbl.pdf [Accessed 2011 Dec 15]
  9. 9.
    Bristol-Myers Squibb Pharma EEIG. Reyataz hard capsules: summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000494/WC500056380.pdf [Accessed 2011 Dec 15]
  10. 10.
    European Medicines Agency. Scientific discussion: detailed description of Reyataz antiviral activity and resistance data in vitro and de novo resistance [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion_-_Variation/human/000494/WC500056385.pdf [Accessed 2011 Sep 28]
  11. 11.
    Bertz R, Wang Y, Mahnke L, et al. Assessment of pharmacokinetic/pharma-codynamic relationships through 48 weeks from a study in HIV+, ART-naive subjects receiving antiretroviral regimens containing atazanavir 400 mg or atazanavir/ritonavir 300/100 mg once daily [abstract no. 565]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
  12. 12.
    Jackson A, Patel N, Lo G, et al. Effects of atazanavir or saquinavir once daily with ritonavir 100 mg and tenofovir/emtricitabine as initial therapy for HIV-1 infection on peripheral glucose disposal: a randomized open-label study [abstract no. 818]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
  13. 13.
    Samson P, Rutstein R, Fenton T, et al. Changes in cholesterol (CH) and triglyceride (TG) levels among pediatric patients treated with atazanavir (ATV), with or without ritonavir boosting, the 1020A NIH PACTG protocol [poster no. 689]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; Denver (CO)Google Scholar
  14. 14.
    Robinson BS, Riccardi KA, Gong YF, et al. BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents. Antimicrob Agents Che-mother 2000 Aug; 44(8): 2093–9CrossRefGoogle Scholar
  15. 15.
    Gong YF, Robinson BS, Rose RE, et al. In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632. Antimicrob Agents Chemother 2000 Sep; 44(9): 2319–26PubMedCrossRefGoogle Scholar
  16. 16.
    Colonno R, Rose R, McLaren C, et al. Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV- 1-infected patients receiving ATV-containing regimens. J Infect Dis 2004 May 15; 189(10): 1802–10PubMedCrossRefGoogle Scholar
  17. 17.
    Schnell T, Schmidt B, Moschik G, et al. Distinct cross-resistance profiles of the new protease inhibitors amprenavir, lopinavir, and atazanavir in a panel of clinical samples [letter]. AIDS 2003 May 23; 17(8): 1258–61PubMedCrossRefGoogle Scholar
  18. 18.
    Colonno RJ, Thiry A, Limoli K, et al. Activities of atazanavir (BMS-232632) against a large panel of human immunodeficiency virus type 1 clinical isolates resistant to one or more approved protease inhibitors. Antimicrob Agents Chemother 2003 Apr; 47(4): 1324–33PubMedCrossRefGoogle Scholar
  19. 19.
    Naeger LK, Struble KA. Effect of baseline protease genotype and phenotype on HIV response to atazanavir/ritonavir in treatment-experienced patients. AIDS 2006 Apr 4; 20(6): 847–53PubMedCrossRefGoogle Scholar
  20. 20.
    Solas C, Colson P, Ravaux I, et al. The genotypic inhibitory quotient: a predictive factor of atazanavir response in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr 2008 Jun 1; 48(2): 177–80PubMedCrossRefGoogle Scholar
  21. 21.
    Lescure FX, Poirier JM, Meynard JL, et al. Factors predictive of virological failure on atazanavir in 310 HIV-infected patients. AIDS 2010 Jun 19; 24(10): 1593–5PubMedCrossRefGoogle Scholar
  22. 22.
    Vrouenraets S, Wit F, Fernandez Garcia E, et al. Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naive HIV-1 infected patients. HIV Med 2011 Nov; 12(10): 620–31PubMedCrossRefGoogle Scholar
  23. 23.
    Soriano V, García-Gasco P, Vispo E, et al. Efficacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: final results of the SLOAT trial. J Antimicrob Chemother 2008 Jan; 61(1): 200–5PubMedCrossRefGoogle Scholar
  24. 24.
    Macassa E, Delaugerre C, Teglas JP, et al. Change to a once-daily combination including boosted atazanavir in HIV-1-infected children. Pediatr Infect Dis J 2006 Sep; 25(9): 809–14PubMedCrossRefGoogle Scholar
  25. 25.
    Nso AP, Larru B, Bellón JM, et al. HIV-infected adolescents: relationship between atazanavir plasma levels and bilirubin concentrations. J Adolesc Health 2011 Jan; 48(1): 100–2PubMedCrossRefGoogle Scholar
  26. 26.
    Rodríguez-Nóvoa S, Martín-Carbonero L, Barreiro P, et al. Genetic factors influencing atazanavir plasma concentrations and the risk of severe hyper-bilirubinemia. AIDS 2007 Jan 2; 21(1): 41–6PubMedCrossRefGoogle Scholar
  27. 27.
    Moltó J, Santos JR, Valle M, et al. Monitoring atazanavir concentrations with boosted or unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monit 2007 Oct; 29(5): 648–51PubMedCrossRefGoogle Scholar
  28. 28.
    Kiser JJ, Rutstein RM, Samson P, et al. Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents. AIDS 2011 Jul 31; 25(12): 1489–96PubMedCrossRefGoogle Scholar
  29. 29.
    Foissac F, Blanche S, Dollfus C, et al. Population pharmacokinetics of atazanavir/ritonavir in HIV-1-infected children and adolescents. Br J Clin Pharmacol 2011 Dec; 72(6): 940–7PubMedCrossRefGoogle Scholar
  30. 30.
    Hong Y, Kowalski KG, Zhang J, et al. Model-based approach for optimization of atazanavir dose recommendations for HIV-infected pediatric patients. Antimicrob Agents Chemother 2011 Dec; 55(12): 5746–52PubMedCrossRefGoogle Scholar
  31. 31.
    National Institute of Allergy and Infectious Diseases. Atazanavir used in combination with other anti-HIV drugs in HIV infected infants, children, and adolescents [ClinicalTrials.gov identifier NCT00006604]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Dec 16]
  32. 32.
    Food and Drug Administration. Reyataz (atazanavir) capsules: clinical review [online]. Available from URL: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM071750.pdf [Accessed 2011 Dec 19]
  33. 33.
    Meyers T, Rutstein R, Samson P, et al. Treatment responses to atazanavir-containing HAART in a drug-naïve pediatric population in South Africa [abstract no. 582]. 15th Conference on Retroviruses and Opportunistic Infections; 2008 Feb 3–6; Boston (MA)Google Scholar
  34. 34.
    Bristol-Myers Squibb Canada. PrReyataz (atazanavir sulfate) capsules: Canadian prescribing information [online]. Available from URL: http://webprod3.hc-sc.gc.ca [Accessed 2011 Dec 19]
  35. 35.
    Bristol-Myers Squibb. PRINCE: study of atazanavir (ATV)/ritonavir (RTV) (PRINCE1) [ClinicalTrials.gov identifier NCT01099579]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Oct 5]
  36. 36.
    Bristol-Myers Squibb. Phase IIIb pediatric ATV powder for oral use (POU) (PRINCE2) [ClinicalTrials.gov identifier NCT01335698]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Oct 5]

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.AdisMairangi Bay, North Shore 0754, AucklandNew Zealand

Personalised recommendations