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Pharmacokinetics of Lopinavir Determined with an ELISA Test in Youths with Perinatally Acquired HIV

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Abstract

Objective

To investigate the plasma levels of lopinavir by enzyme-linked immunosorbent assay (ELISA) in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (HIV).

Methods

Plasma levels of lopinavir (Cmin) were determined by ELISA test in patients treated with lopinavir/ritonavir-based combined antiretroviral therapy who had achieved virological response after 4 wk of therapy. Reference lopinavir concentrations were Cmin 1–8 μg/mL. Correlation between lopinavir plasma concentration and continuous variables was evaluated by mean of Pearson correlation coefficient. Differences in lopinavir (LPV) concentration for binary categorical variables were assessed by Mann-Whitney test, while for variables with more than two categories Kruskal-Wallis test was used.

Results

Thirty-four patients were enroled; median age was 133 mo (15–265). The median lopinavir dose tested was 383.5 mg/kg (IQR: 266.6–400 mg/kg), with a median plasma concentration of 8.8 μg/mL (IQR: 5–14 μg/mL). Lopinavir Cmin was <1 μg/mL in only one sample (2.9 %), while 14 samples had Cmin between 1 and 8 μg/mL (41.2 %) and 19 (55.9 %) > 8 μg/mL. No significant correlations were found between plasma concentrations of lopinavir and the continuous variables considered in the study. A negative but, not completely significant, correlation was found between plasma drug concentration and body mass index (r = −0.29; p = 0.09).

Conclusions

The use of a simple and relatively cost-effective methodology might render therapeutic drug monitoring (TDM) appeal in the daily clinical practice.

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References

  1. Fraaij PL, Rakhmanina N, Burger DM, de Groot R. Therapeutic drug monitoring in children with HIV/AIDS. Ther Drug Monit. 2004;26:122–6.

    Article  PubMed  Google Scholar 

  2. Nso AP, Larru B, Bellón JM, Mellado MJ, Ramos JT, González MI, et al. Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection. Indian J Pediatr. 2010;77:397–402.

    Article  PubMed  Google Scholar 

  3. Aarnouste RE, Schapiro JM, Boucher CA, Hekster YA, Burger DM. Therapeutic drug monitoring: An aid to optimizing response to antiretroviral drugs? Drugs. 2003;63:741–53.

    Article  Google Scholar 

  4. US Department of Health and Human Services, Panel on Antiretroviral Therapy and Medical Management of HIV Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Available at: http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Updated November 5, 2012.

  5. TDM-ELISA Lopinavir. Package insert and operative instructions. 2010. Retrieved from: www.biostrands.com.

  6. World Health Organization. Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach 2010 revision. Geneva, Switzerland: WHO; 2010. Available at: http://whqlibdoc.who.int/publications/2010/9789241599801_eng.pdf.

  7. PENTA Steering Committee. Paediatric European network for treatment of AIDS response to 2010 revision of World Health Organization recommendations on ‘antiretroviral therapy for HIV infection in infants and children’. HIV Med. 2011;12:385–6.

    Article  Google Scholar 

  8. Lodha R, Mangiani M. Antiretroviral therapy in children: Recent advances. Indian J Pediatr. 2012;79:1625–33.

    Article  PubMed  Google Scholar 

  9. Hsu A, Isaacson J, Brun S, Bernstein B, Lam W, Bertz R, et al. Pharmacokinetic-pharmacodynamic analysis of lopinavir/ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus infected patients. Antimicrob Agents Chemother. 2003;47:350–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Jullien V, Urien S, Hirt D, Delaugerre C, Rey E, Teglas JP, et al. Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years. Antimicrob Agents Chemother. 2006;50:3548–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Podzamczer D, King MS, Klein CE, Flexner C, Katlama C, Havlir DV, et al. High-dose lopinavir/ritonavir in highly treatment-experienced HIV-1 patients: Efficacy, safety, and predictors of response. HIV Clin Trials. 2007;8:193–204.

    Article  PubMed  Google Scholar 

  12. Rakhmanina N, van den Anker J, Baghdassarian A, Soldin S, Williams K, Neely MN. Population pharmacokinetics of lopinavir predict suboptimal therapeutic concentrations in treatment-experienced human immunodeficiency virus-infected children. Antimicrob Agents Chemother. 2009;53:2532–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Kaletra product labeling [package insert]. North Chicago, IL: Abbott Laboratories; Available at: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=1584.

  14. Acosta EP, Gerber JG; Adult Pharmacology Committee of the AIDS Clinical Trials Group. Position paper on therapeutic drugmonitoring of antiretroviral agents. AIDS Res Hum Retroviruses. 2002;18:825–34.

    Google Scholar 

  15. Back D, Gatti G, Fletcher C, Garaffo R, Haubrich R, Hoetelmans R, et al. Therapeutic drug monitoring in HIV infection: Current status and future directions. AIDS. 2002;16:S5–37.

    Google Scholar 

  16. Bastiani E, Benedetti F, Berti F, Campaner P, Donadel E, Montagna M, et al. Development and evaluation of an immunoassay for the monitoring of the anti-HIV drug Amprenavir. J Immunol Methods. 2007;325:35–41.

    Article  CAS  PubMed  Google Scholar 

  17. Uglietti A, Ravasi G, Meroni V, Narciso P, Ladisa N, Martini S, et al. Nelfinavir + M8 plasma levels determined with an ELISA test in HIV infected patients with or without HCV and/or HBV coinfection: The VIRAKINETICS II study. Curr HIV Res. 2009;7:293–301.

    Article  CAS  PubMed  Google Scholar 

  18. Rakhmanina NY, van den Anker JN, Soldin SJ, van Schaik RH, Mordwinkin N, Neely MN. Can therapeutic drug monitoring improve pharmacotherapy of HIV infection in adolescents? Ther Drug Monit. 2010;32:273–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Rosso R, Di Biagio A, Dentone C, Gattinara GC, Martino AM, Viganò A, et al. Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following twice or once daily administration. J Antimicrob Chemother. 2006;57:1168–71.

    Article  CAS  PubMed  Google Scholar 

  20. Best BM, Capparelli EV, Diep H, Rossi SS, Farrell MJ, Williams E, et al. Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children. J Acquir Immune Defic Syndr. 2011;58:385–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Van Rossum AM, Bergshoeff AS, Fraaij PL, Hugen PW, Hartwig NG, Geelen SP, et al. Therapeutic drug monitoring of indinavir and nelfinavir to assess adherence to therapy in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2002;21:743–7.

    Article  PubMed  Google Scholar 

  22. Gatti G, Castelli-Gattinara G, Cruciani M, Bernardi S, De Pascalis CR, Pontali E, et al. Pharmacokinetics and pharmacodynamics of nelfinavir administered twice or thrice daily to human immunodeficiency virus type 1-infected children. Clin Infect Dis. 2003;36:1476–82.

    Article  CAS  PubMed  Google Scholar 

  23. Battles H, Wiener L. From adolescence through young adulthood psychosocial adjustment associated with long-term survival of HIV. J Adolesc Health. 2002;30:161–8.

    Article  PubMed  Google Scholar 

  24. Mellins C, Brackis-Cott E, Dolezal C, Abrams E. The role of psychosocial and family factors in adherence to antiretroviral treatment in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2004;23:1035–41.

    Article  PubMed  Google Scholar 

  25. Murphy DA, Wilson CM, Durako SJ, Muenz LR, Belzer M, Adolescent Medicine HIV/AIDS Research Network. Antiretroviral medication adherence among the REACH-HIV-infected adolescent cohort in the USA. AIDS Care. 2001;13:27–40.

    Article  CAS  PubMed  Google Scholar 

  26. Williams PL, Storm D, Montepiedra G, Nichols S, Kammerer B, Sirois PA, et al. Predictors of adherence to antiretroviral medications in children and adolescents with HIV infection. Pediatrics. 2006;118:1745–57.

    Article  Google Scholar 

  27. Biadgilign S, Deribew A, Amberbir A, Deribe K. Adherence to highly active antiretroviral therapy and its correlates among HIV infected pediatric patients in Ethiopia. BMC Pediatr. 2008;8:53.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Giannattasio A, Albano F, Giacomet V, Guarino A. The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart, in a cohort of HIV-infected children. Expert Opin Pharmacother. 2009;10:2773–8.

    Article  CAS  PubMed  Google Scholar 

  29. Marhefka SL, Farley JJ, Rodrigue JR, Sandrik LL, Sleasman JW, Tepper VJ. Clinical assessment of medication adherence among HIV-infected children: examination of the Treatment Interview Protocol (TIP). AIDS Care. 2004;3:323–38.

    Article  Google Scholar 

  30. Merzel C, Vandevanter N, Irvine M. Adherence to antiretroviral therapy among older children and adolescents with HIV: a qualitative study of psychosocial contexts. AIDS Patient Care STDS. 2009;22:977–87.

    Article  Google Scholar 

  31. Rosso R, Di Biagio A, Maggiolo F, Nulvesu L, Callegaro AP, Taramasso L, et al. Patient-reported outcomes and low-level residual HIV-RNA in adolescents perinatally infected with HIV-1 after switching to one-pill fixed-dose regimen. AIDS Care. 2012;24:54–8.

    Article  PubMed  Google Scholar 

  32. van der Flier M, Verweel G, van der Knaap LC, van Jaarsveld P, Driessen GJ, van der Lee M, et al. Pharmacokinetics of lopinavir in HIV type-1-infected children taking the new tablet formulation once daily. Antivir Ther. 2008;13:1087–90.

    PubMed  Google Scholar 

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Acknowledgments

The authors are indebted to Professor PierLuigi Navarra, for encouraging the continuation of the paper. They would also like to thank the children and their parents/ legal guardians for their participation to the study.

Contributions

RR passed away during the development of this manuscript. She reviewed the outline and first draft in detail for clinical accuracy and intellectual content. AD, RR, RP, VG, FG, LT, FM, EF, LN had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. AD, RR: Study concept and design; MS, AS, IS: Statistical expertise; AD, RP, CV, LT: Drafting of the manuscript; LD, RP, LT: Critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript.

Conflict of Interest

The authors did not receive any financial support for their contribution to this study, but AD has received prior research funding and/or consultancy honoraria from Abbott, Bristol Myers Squibb, Gilead, Janssen-Cilag, Merck Sharp & Dohme, Roche, and ViiV.

Role of Funding Source

The study was supported by Programma Nazionale di Ricerca sull’AIDS, Istituto Superiore di Sanità, Italy, Grants 30F/06. Codice Eudract 2007–00389638 “Studio di farmacocinetica e farmacodinamica nella ottimizzazione della terapia antiretrovirale”.

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Authors and Affiliations

  1. Infectious Diseases Clinic, San Martino Hospital, University of Genoa, Genoa, Italy

    Roberta Prinapori, Raffaella Rosso, Antonio Di Biagio, Franca Miletich, Elisa Furfaro, Lucia Taramasso, Francesca Ginocchio, Loredana Nulvesu, Laura De Hoffer & Claudio Viscoli

  2. Luigi Sacco Hospital, University of Milan, Milano, Italy

    Vania Giacomet

  3. Section of Biostatistics, Department of Health Sciences, University of Genoa, Genoa, Italy

    Maria Pia Sormani, Irene Schiavetti & Alessio Signori

  4. Clinica Malattie Infettive, IRCCS Azienda Ospedaliera Universitaria San Martino - IST, Genova, 16132, Italy

    Antonio Di Biagio

Authors
  1. Roberta Prinapori
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  2. Raffaella Rosso
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  3. Antonio Di Biagio
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  4. Franca Miletich
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  5. Elisa Furfaro
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  6. Lucia Taramasso
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  7. Francesca Ginocchio
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  9. Loredana Nulvesu
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  13. Laura De Hoffer
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  14. Claudio Viscoli
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Corresponding author

Correspondence to Antonio Di Biagio.

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Prinapori, R., Rosso, R., Di Biagio, A. et al. Pharmacokinetics of Lopinavir Determined with an ELISA Test in Youths with Perinatally Acquired HIV. Indian J Pediatr 81, 856–860 (2014). https://doi.org/10.1007/s12098-013-1198-1

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  • DOI: https://doi.org/10.1007/s12098-013-1198-1

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