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Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

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DOI: 10.4236/pp.2012.31013    3,770 Downloads   6,698 Views   Citations

ABSTRACT

Antiretroviral therapy in HIV patients is known for its negative effect on the cardiovascular system. One of the major adverse events in patients on lopinavir is increasing lipids. Hyperlipidaemia together with chronic inflammation by HIV-infection itself makes these patients prone for cardiovascular diseases.The purpose of this study (a sub study within the FREE-study) was to determine if higher plasma lopinavir (LPV) concentrations lead to increase of serum lipids. Plasma drug concentrations were analysed up to week 24 in a prospective cohort of HIV antiretroviral therapy naive patients who started on a regimen of zidovudine, lamivudine and ritonavir-boosted lopinavir (FREE study). Prospectively we measured plasma lopinavir concentrations from baseline to week 24 in 72 naive HIV-patients starting on lopinavir (59 males and 13 females). A total of 210 samples were analysed, with at least 2 samples in every patient. Mean LPV trough concentration was 4.3 mg/L (± 2.1). The median intra-subject variation in LPV level was 38% (range 4% - 111%). Serum lipids were not correlated to LPV plasma concentrations possibly due to the wide intra-individual variability in LPV trough levels. Monitoring of plasma lopinavir and subsequent dose adjustment of LPV will not be useful to prevent hyperlipidaemia in HIV-patients treated with lopinavir.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

H. Hofstede, P. Koopmans, D. Burger, H. Sprenger, C. Napel, R. Vriesendorp and C. Richter, "Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study," Pharmacology & Pharmacy, Vol. 3 No. 1, 2012, pp. 90-96. doi: 10.4236/pp.2012.31013.

References

[1] E. Martinez, P. Domingo, M. J. Galindo, A. Milinkovic, J.A. Arroyo, F. Baldovi, M. Larrousse, A.Leon, E. de Lazzari and J. M. Gatell, “Risk of Metabolic Abnormalities in Patients Infected with HIV Receiving Antiretrovi-ral Therapy That Contains Lopinavir-Ritonavir,” Clinical Infectious Diseases, Vol. 38, No. 7, 2004, pp. 1017-1023. doi:10.1086/382531
[2] L. Calza, R. Manfredi, B. Farneti and F. Chiodo, “Incidence of Hyperlipidaemia in a Cohort of 212 HIV-Infected Patients Receiving a Protease Inhibitor-Based Antiretroviral Therapy,” International Journal of Antimicrobial Agents, Vol. 22, No. 1, 2003, pp. 54-59. doi:10.1016/S0924-8579(03)00100-6
[3] A. Lafeuillade, G. Hittinger, G. Philip, V. Lambry, P. Jolly and C. Poggi, “Metabolic Evaluation of HIV-Infected Patients Receiving a Regimen Containing Lopinavir/Ritonavir (Kaletra),” HIV Clinical Trials, Vol. 5, No. 6, 2004, pp. 392-398. doi:10.1310/Q0TG-0V50-9JML-638U
[4] M. L. Montes, F. Pulido, C. Barros, E. Condes, R. Rubio, C. Cepeda, F. Dronda, A. Antela,, J. Sanz, E. Navas, P. Miralles, J. Berenguer, S. Perez, A. Zapata, J. J. Gonzalez-Garcia, J. M. Pena, J. J. Vazquez and J. R. Arribas, “Lipid Disorders in Antiretroviral-Naive Patients Treated with Lopinavir/Ritonavir-Based HAART: Frequency, Characterization and Risk Factors,” Journal of Antimicrobial Chemotherapy, Vol. 55, No. 5, 2005, pp. 800-804. doi:10.1093/jac/dki063
[5] J. Oh and R. A. Hegele, “HIV-Associated Dyslipidaemia: Pathogenesis and Treatment,” Lancet Infectious Diseases, Vol. 7, No. 12, 2007, pp. 787-796. doi:10.1016/S1473-3099(07)70287-6
[6] J. P. Dieleman, I. C. Gyssens, M. E. van der Ende, S. de Marie and D. M. Burger, “Urological Complaints in Relation to Indinavir Plasma Concentrations in HIV-Infected Patients,” AIDS, Vol. 13, No. 4, 1999, pp. 473-478. doi:10.1097/00002030-199903110-00005
[7] F. Gutierrez, A. Navarro, S. Padilla, R. Anton, M. Masia, J. Borras and A. Martin-Hidalgo, “Prediction of Neuro- psychiatric Adverse Events Associated with Long-Term Efavirenz Therapy, Using Plasma Drug Level Monitoring,” Clinical Infectious Diseases, Vol. 41, No. 11, 2005, pp. 1648-1653. doi:10.1086/497835
[8] R. Dicenzo, A. Luque, P. Larppanichpoonphol and R. Reichman, “Association of Total Bilirubin with Indinavir and Lopinavir Plasma Concentrations in HIV-Infected Patients Receiving Three Different Double-Boosted Dosing Regimens,” Journal of Antimicrobial Chemotherapy, Vol. 58, No. 2, 2006, pp. 393-400. doi:10.1093/jac/dkl238
[9] G. Gatti, B. A. Di, R. Casazza, C. De Pascalis, M. Bassetti, M. Cruciani, S. Vella and D. Bassetti, “The Relationship between Ritonavir Plasma Levels and Side-Effects: Implications for Therapeutic Drug Monitoring,” AIDS, Vol. 13, No. 15, 1999, pp. 2083-2089. doi:10.1097/00002030-199910220-00011
[10] H. J. M. Ter Hofstede, P. P. Koopmans and D. M. Burger, “Stavudine Plasma Concentrations and Lipoatrophy,” Journal of Antimicrobial Chemotherapy, Vol. 61, No. 4, 2008, pp. 933-938. doi:10.1093/jac/dkn041
[11] L. Valerio, E. Fontas, C. Pradier, T. Lavrut, R. Garraffo, B. Dunais, E. Cua and P. Dellamonica, “Lopinavir/Ritonavir Combination and Total/HDL Cholesterol Ratio,” Journal of Infection, Vol. 50, No. 3, 2005, pp. 229-235. doi:10.1016/j.jinf.2004.01.014
[12] R. D. de Gonzalez, F. Blanco, T. Garcia-Benayas, I. Jimenez-Nacher, J. Gonzalez-Lahoz and V. Soriano, “Correlation between Lopinavir Plasma Levels and Lipid Abnormalities in Patients Taking Lopinavir/Ritonavir,” AIDS Patient Care STDS, Vol. 17, No. 9, 2003, pp. 443- 445. doi:10.1089/108729103322395465
[13] J. A. Droste, C. P. Verweij-van Wissen and D. M. Burger, “Simultaneous Determination of the HIV Drugs Indinavir, Amprenavir, Saquinavir, Ritonavir, Lopinavir, Nelfinavir, the Nelfi-navir Hydroxymetabolite M8, and Nevirapine in Human Plasma by Reversed-Phase High-Performance Liquid Chromatography,” Therapeutic Drug Monitoring, Vol. 25, No. 3, 2003, pp. 393-399. doi:10.1097/00007691-200306000-00023
[14] C. Torti, E. Quiros-Roldan, V. Tirelli, M. Regazzi-Bonora, F. Moretti, P. Pierotti, A. Orani, P. Maggi, A. Cargnel, A. Patroni, A. De Luca and G. Carosi, “Lopinavir Plasma Levels in Salvage Regimes by a Population of Highly Active Antiretroviral Therapy-Treated HIV-1- Positive Patients,” AIDS Patient Care STDS, Vol. 18, No. 11, 2004, pp. 629-634. doi:10.1089/apc.2004.18.629
[15] M. Boffito, D. J. Back, P. G. Hoggard, A. Caci, S. Bonora, S. R. Raiteri, A. Sinicco, H. E. Reynolds, S. Khoo and G. Di Perri, “Intra-Individual Variability in Lopinavir Plasma Trough Concentrations Supports Therapeutic Drug Monitoring,” AIDS, Vol. 17, No. 7, 2003, pp. 1107- 1108. doi:10.1097/00002030-200305020-00029
[16] F. Gutierrez, S. Padilla, A. Navarro, M. Masia, I. Hernandez, J. Ramos, A. Esteban and A. Martin-Hidalgo, “Lopinavir Plasma Concentrations and Changes in Lipid Levels during Salvage Therapy with Lopinavir/Ritonavir-Containing Regimens,” Journal of Acquired Immune Deficiency Syndromes, Vol. 33, No. 5, 2003, pp. 594-600. doi:10.1097/00126334-200308150-00007
[17] F. Gutierrez, S. Padilla, A. Navarro, M. Masia and I. Hernandez, “Lipid Abnormalities in HIV-Infected Patients and Lopinavir Plasma Concentrations,” Journal of Acquired Immune Deficiency Syndromes, Vol. 36, No. 5, 2004, pp. 1107-1109. doi:10.1097/00126334-200408150-00017
[18] P. Clevenbergh, R. Garraffo and P. Dellamonica, “Impact of Various Antiretroviral Drugs and Their Plasma Concentrations on Plasma Lipids in Heavily Pretreated HIV- Infected Patients,” HIV Clinical Trials, Vol. 4, No. 5, 2003, pp. 330-336. doi:10.1310/8TXF-P814-8JPF-7TRY
[19] A. Leon, E. Martinez, M. Sarasa, Y. Lopez, J. Mallolas, E. De Lazzari, M. Laguno, A. Milincovic, J. L. Blanco, M. Larrousse, M. Lonca and J. M. Gatell, “Impact of Steady-State Lopinavir Plasma Levels on Plasma Lipids and Body Composition after 24 Weeks of Lopinavir/Ritonavir-Containing Therapy Free of Thymidine Analogues,” Journal of An-timicrobial Chemotherapy, Vol. 60, No. 4, 2007, pp. 824-830. doi:10.1093/jac/dkm285
[20] C. Torti, E. Quiros-Roldan, M. Regazzi-Bonora, A. De,Luca, S. Lo, Caputo, S. Di Giambenedetto, A. Patroni, P. Villani, V. Micheli and G. Carosi, “Lipid Abnormalities in HIV-Infected Patients Are Not Correlated with Lopinavir Plasma Concentrations,” Journal of Acquired Immune Deficiency Syndromes, Vol. 35, No. 3, 2004, pp. 324-326. doi:10.1097/00126334-200403010-00017
[21] M. Bongiovanni, T. Bini, E. Chiesa, P. Cicconi, F. Adorni and A. Monforte d’Arminio, “Lopinavir/Ritonavir vs. Indinavir/Ritonavir in Antiretroviral Naive HIV-Infected Patients: Immunovirological Outcome and Side Effects,” Antiviral Research, Vol. 61, No. 1, 2004, pp. 53-56. doi:10.1016/j.antiviral.2003.12.002
[22] T. Antoniou, L. Park-Wyllie and E. Boyle, “A Comparison of Dyslipidemias Associated with Either Lopinavir/Ritonavir- or Indinavir/Ritonavir-Based Antiretro- viral Therapy,” Journal of Acquired Immune Deficiency Syndromes, Vol. 37, No. 5, 2004, pp. 1666-1667. doi:10.1097/00126334-200412150-00023
[23] M. Bongiovanni, T. Bini, P. Cicconi, S. Landonio, P. Meraviglia, L. Testa, A. Di Biagio, E. Chiesa, F. Tordato, P. Biasi, F. Adorni and A. D. Monforte, “Predictive Fac- tors of Hyperlipidemia in HIV-Infected Subjects Receiv-ing Lopinavir/Ritonavir,” AIDS Res Hum Retroviruses, Vol. 22, No. 2, 2006, pp. 132-138. doi:10.1089/aid.2006.22.132
[24] M. Schambelan, C. A. Benson, A. Carr, J. S. Currier, M. P. Dube, J. G. Gerber, S. K. Grinspoon, C. Grunfeld, D. P. Kotler, K. Mulligan, W. G. Powderly and M. S. Saag, “Management of Metabolic Complications Associated with Antiretroviral Therapy for HIV-1 Infection: Recommendations of an International AIDS Society-USA Panel,” Journal of Acquired Immune Deficiency Syndromes, Vol. 31, No. 3, 2002, pp. 257-275. doi:10.1097/00126334-200211010-00001
[25] M. van de Valk, J. J. Kastelein, R. L. Murphy, F. van Leth, C. Kat-lama, A. Horban, M. Glesby, G. Behrens, B. Clotet, R. K. Stellato, H. O. Molhuizen and P. Reiss, “Nevirapine-Containing Antiretroviral Therapy in HIV-1 Infected Patients Results in an Anti-Atherogenic Lipid Profile,” AIDS, Vol. 15, No. 18, 2001, pp. 2407-2414. doi:10.1097/00002030-200112070-00008
[26] K. Anas-tos, D. Lu and Q.Shi, “Association of Serum Lipid Levels with HIV Serostatus, Specific Antiretroviral Agents, and Treatment Regimens,” Journal of Acquired Immune Deficiency Syndromes, Vol. 45, No. 1, 2007, pp. 34-42. doi:10.1097/QAI.0b013e318042d5fe
[27] M. Gandhi, F. Aweeka, R. M. Greenblatt and T. F. Blaschke, “Sex Differences in Pharmacokinetics and Pharmacodynamics,” Annual Review of Pharmacology and Toxicology, Vol. 44, 2004, pp. 499-523. doi:10.1146/annurev.pharmtox.44.101802.121453

  
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