A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: Week 48 results of the A5146 study

HIV Clinical Trials

Volumn 12, Issue 4, 2011, Pages 201-214

  Albrecht, Mary ^a   Lisa Mukherjee, A ^b   Tierney, Camlin ^b   Morse, Gene D ^c   Dykes, Carrie ^d   Klingman, Karin L ^e   Demeter, Lisa M ^d  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^c UNIVERSITY AT BUFFALO   (United States)

^d UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

antiretroviral therapy; clinical trials; HIV drug resistance; pharmacokinetics; protease inhibitors; therapeutic drug monitoring

Indexed keywords

AMPRENAVIR; ANTIRETROVIRUS AGENT; ATAZANAVIR; FOSAMPRENAVIR; INDINAVIR; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; TIPRANAVIR; VIRUS RNA;

ABNORMAL LABORATORY RESULT; ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; CD4 LYMPHOCYTE COUNT; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; COUGHING; CREATINE KINASE BLOOD LEVEL; DIARRHEA; DRUG DOSE ESCALATION; DRUG MONITORING; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HEALTH CARE QUALITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HYPERGLYCEMIA; LIVER FUNCTION TEST; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALAISE; MALE; NAUSEA; NEUTROPENIA; OPEN STUDY; PAIN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SECONDARY ANALYSIS; SIDE EFFECT; TREATMENT RESPONSE; TRIACYLGLYCEROL BLOOD LEVEL; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VIRUS LOAD; VOMITING;

ADULT; CD4 LYMPHOCYTE COUNT; DRUG MONITORING; FEMALE; FOLLOW-UP STUDIES; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MALE; MIDDLE AGED; VIRAL LOAD;

EID: 80455127179     PISSN: 15284336     EISSN: 19455771     Source Type: Journal    
DOI: 10.1310/HCT1204-201     Document Type: Article

References (54)

1. US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. http://aidsinfo.nih.gov/Guidelines/aspx. Accessed November 3, 2008.
2. Hammer SM, Eron JJ, Reiss P, et al. Antiretroviral treatment of adult HIV infection. 2008 recommendations of the International AIDS Society-USA Panel. JAMA. 2008; 300:555-570.
3. Bartlett JA, Buda JJ, von Scheele B, Mauskopf JA, Davis A, King MS, Lanier ER. Minimizing resistance consequences after virologic failure on initial combination therapy. J Acquir Defic Syndr. 2006;41:323-331.
4. Montaner J, Guimaraes D, Chung J, Gafoor Z, Salgo M, De Masi R. Prognostic staging of extensively pretreated patients with advanced HIV-1 disease. HIV Clin Trials. 2005;6:281-290.
5. Steigbigel RT, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008;359:339-354.
6. Gulick RM, Lalezari J, Goodrich J, et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008;359:1429-1441.
7. Fatkenheuer G, Nelson M, Lazzarin A, et al. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med. 2008;359:1442-1455.
8. Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337(11):725-33.
9. Madruga JV, Berger D, Mcmurchie M, et al; the TITAN Study Group. Efficacy and safety of darunavir-ritonavir compared with lopinavir-ritonavir at 48 weeks in treatmentexperienced, HIV-infected patients in TITAN: A randomized, controlled phase III study. Lancet. 2007;370:49-58.
10. Clotet B, Bellos N, Molina JM, et al; POWER 1 and 2 Study Groups. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patient with HIV-1infection in POWER 1 and 2: A pooled subgroup analysis of data from two randomized trials. Lancet. 2007;369:1169-1178
11. Guidelines: Clinical management and treatment of HIV infected adults in Europe. www.europeanaidsclinicalsociety. org. Accessed March 4, 2011.
12. Aarnoutse RE, Schapiro JM, Boucher CA, Hekster YA, Burger DM. Therapeutic drug monitoring: An aid to optimizing response to antiretroviral drugs? Drugs. 2003;63:741-753
13. Burger D, Hugen P, Reiss P, et al; ATHENA Cohort Study Group. Therapeutic drug monitoring of nelfinavir and indinavir in treatment-naïve HIV-1 infected individuals. AIDS. 2003;17:1157-1165.
14. Boffito M, Acosta E, Burger D, et al. Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs. Antivir Ther. 2005;10:469-477.
15. Mello AF, Buclin T, Decosterd LA, et al. Successful efavirenz dose reduction guided by therapeutic drug monitoring. Antivir Ther. 2011;16:189-197.
16. Colombo S, Buclin T, Cavassini M, et al. Population pharmacokinetics of atazanavir in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 2006;50(11):3801-3808.
17. Durant J, Clevenbergh P, Garraffo R, et al. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: Pharmacological data from the Viradapt Study. AIDS (Lond). 2000;14(10):1333-1339.
18. Shulman N, Zolopa A, Havlir D, et al. Virtual inhibitory quotient predicts response to ritonavir boosting of indinavirbased therapy in human immunodeficiency virus-infected patients with ongoing viremia. Antimicrob Agents Chemother. 2002;46(12):3907-3916.
19. Hsu A, Isaacson J, Brun S, et al. Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodefi- ciency virus-infected patients. Antimicrob Agents Chemother. 2003;47(1):350-359.
20. Marcelin AG, Lamotte C, Delaugerre C, et al. Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Antimicrob Agents Chemother. 2003;47(2):594-600.
21. Casado JL, Moreno A, Sabido R, et al. Individualizing salvage regimens: The inhibitory quotient (Ctrough/IC50) as predictor of virological response. AIDS (Lond). 2003;17(2): 262-264.
22. Taburet AM, Raguin G, Le Tiec C, et al. Interactions between amprenavir and the lopinavir-ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus. Clin Pharmacol Ther. 2004;75(4):310-323.
23. De Luca A, Baldini F, Cingolani A, Di Giambenedetto S, Hoetelmans RM, Cauda R. Deep salvage with amprenavir and lopinavir/ritonavir: Correlation of pharmacokinetics and drug resistance with pharmacodynamics. J Acquir Immune Defic Syndr. 2004; 35(4):359-366.
24. Gonzalez de Requena D, Gallego O, Valer L, Jimenez- Nacher I, Soriano V. Prediction of virological response to lopinavir/ritonavir using the genotypic inhibitory quotient. AIDS Res Human Retroviruses. 2004;20(3):275-278.
25. Castagna A, Gianotti N, Galli L, et al. The NIQ of lopinavir is predictive of a 48-week virological response in highly treatment-experienced HIV-1-infected subjects treated with a lopinavir/ritonavir-containing regimen. Antivir Ther. 2004;9(4):537-543.
26. Barrios A, Rendon AL, Gallego O, et al. Predictors of virological response to atazanavir in protease inhibitor- experienced patients. HIV Clin Trials. 2004;5(4): 201-205.
27. Marcelin AG, Dalban C, Peytavin G, et al. Clinically relevant interpretation of genotype and relationship to plasma drug concentrations for resistance to saquinavir-ritonavir in human immunodeficiency virus type 1 protease inhibitorexperienced patients. Antimicrob Agents Chemother. 2004;48(12):4687-4692.
28. Marcelin AG, Cohen-Codar I, King MS, et al. Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients. Antimicrob Agents Chemother. 2005;49(5): 1720-1726.
29. Winston A, Hales G, Amin J, van Schaick E, Cooper DA, Emery S. The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals. AIDS (Lond). 2005;19(13):1393-1399.
30. Demeter LM, Jiang H, Mukherjee AL, et al. Therapeutic drug monitoring of protease inhibitors using a normalized inhibitory quotient in antiretroviral-experienced HIV-1- infected patients (AIDS Clinical Trials Group A5146). AIDS. 2009;23:357-368.
31. www.fda.gov/cder/foi/label/2005/021814lbl.pdf. Accessed August 4, 2007.
32. www.fda.gov/cder/foi/nda/2003/021567-reyataz-toc.htm. Accessed August 4, 2007.
33. www.fda.gov/ohrms/dockets/ac/05/slides/2005-4139S1-09-FDA-Zheng.ppt. Accessed May 19, 2005.
34. Demeter LM, Mukherjee AL, DiFrancesco R, et al. The design and implementation of A5146, a prospective trial assessing the utility of therapeutic drug monitoring using an inhibitory quotient in antiretroviral- experienced HIVinfected patients. HIV Clin Trials. 2008;9:61-72.
35. Reboussin DM, DeMets DL, Kim KM, Lan KK. Computations for group seqeuntial boundaries using the Lan- DeMets spending function method. Control Clin Trials. 2000;21:190-207.
36. http://rcc.tech-res.com/tox-tables.htm. Accessed December 28, 2004.
37. Stohr W, Back D, Dunn D, et al; for the UK CHIC Study. Factors influencing efavirenz and nevirapine plasma concentration: Effect of ethnicity, weight, and co-medication. Antivir Ther. 2008;13:675-685.
38. Lakhman SS, Ma Q, Morse GD. Pharmacogenomics of CYP3A: Considerations for HIV treatment. Pharmacogenomics. 2009;10:1323-1339.
39. Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol. 2008;66:179-195.
40. Fabbiani M, Di Giambenedetto S, Bracciale L, et al. Pharamcokinetic variability of antiretroviral drugs and correlation with virological outcome: 2 years of experience in routine clinical practice. J Antimicrob Chemother. 2009;64: 109-117.
41. Molto J, Santos JR, Valle M, Miranda J, Blanco A, Negredo E, Clotet B. Monitoring atazanavir concentrations with boosted or unboosted regimens in HIV-infected patients in routine clinical practice. Ther Drug Monitoring. 2007;29:648-651.
42. Khoo SH, Lloyd J, Dalton M, et al. Pharmacologic optimization of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (POPIN)-a randomized controlled trial of therapeutic drug monitoring and adherence support. J Acquir Immune Defic Syndr. 2006; 41(4):461-467.
43. del Rio C. Current concepts in antiretroviral therapy failure. Top HIV Med. 2006;14:102-106.
44. Park-Wyllie LY, Levine MA, Holbrook A, et al. Outcomes of dosage adjustments used to manage antiretroviral drug interactions. Clin Infect Dis. 2007;45(7):933-936.
45. van Luin MK, Kuks PF, Burger DM. Use of therapeutic drug monitoring in HIV disease. Curr Opin HIVAIDS. 2008;3(3):266-271.
46. Cleijsen RM, Van de Ende ME, Kroon FP, et al. Therapeutic drug monitoring of the HIV protease inhibitor atazanavir in clinical practice. J Antimicrob Chemother. 2007;60(4): 897-900.
47. Hoefnagel JG, van der Lee MJ, Koopmans PP, et al. The genotypic inhibitory quotient and the cumulative number of mutations predict the response to lopinavir therapy. AIDS. 2006;20:1069-1071.
48. Barrail-Tran A, Morand-Joubert L, Poizat G, et al. Predictive values of the human immunodeficiency virus phenotype and genotype and of amprenavir and lopinavir inhibitory quotients in heavily pretreated patients on a ritonavir-boosted dual protease inhibitor regimen. Antimicrob Agents Chemother. 2008; 52:1642-1646.
49. Picchio G, Vingerhoets J, Tambuyzer L, Coakley E, Haddad M, Witek J. Prevalence of susceptibility to etravirine by genotype and phenotype in samples received for routine HIV-1 resistance testing in the USA [published online ahead of print May 10, 2011]. AIDS Res Hum Retroviruses.
50. Schiller DS, Youssef-Bessler M. Etravirine: A second generation nonnucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant strains of HIV. Clin Ther. 2009;31:692-704
51. Azlin H, Tirry I, Vingerhoets J, et al. TMC 278, a nextgeneration nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV- 1. Antimicrob Agents Chemother. 2010;54:718-727.
52. Goebel F, Yakovlev A, Pozniak AL, et al. Short-term antiviral activity of TMC 278- a novel NNRTI in treatment-naïve HIV-1 infected subjects. AIDS. 2006;20:1721-1726.
53. Scherrer AU, von Wyl V, Boni J, et al; and the Swiss Study Cohort. Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside /tide reverse transcriptase inhibitors. J Acquir Immune Defic Syndr. 2011; 57:24-31.
54. Crawford KW, Spritzler J, Kalayjian RC, et al. Age-related changes on plasma concentrations of the HIV protease inhibitor lopinavir. AIDS Res Hum Retroviruses. 2010;26: 635-643.