Prevalence and Characteristic of HIV Protease Mutation at L76V-Patients who Had Virological Failure during Lopinavir/ritonavir
DOI:
https://doi.org/10.14456/dcj.2013.30Keywords:
L76V, Lopinavir/ ritonavir, virological failureAbstract
This descriptive, retrospective study was design to evaluate the prevalence and characteristic of HIV protease mutation at L76V-Patients who had virological failure during LPV/r and good adherence. There were patients who had HIV protease mutation L76V (L76V+ group) and patients who did not had HIV protease mutation L76V (L76V- group). This study was collected at virological failure during LPV/r. Genotypic method was done. Risk factor and datas were collected after initial LPV/r therapy 3-6 months from medical record, until 1 Jan 2007 to 31 Dec 2010. Patients were under 18 years old. There were 16 patients who were included in this study.There were 3 patients(18.75) who were in L76V+ group and 13 patients (81.25%) who were in L76V- group. The prevalence of protease mutation L76V-patients who received LPV/r, had virological failure and good adherence was 18.75. Age, BMI and Plasma viral load were not different between 2 groups. Patients in L76V+ group received double boosted PI on virological failure during LPV/r more than L76V- group. Conclusion The prevalence of protease mutation L76Vpatients who received LPV/r, had virological failure and good adherence was 18.75. Third-line options in Antiretroviral drug should be carefully considered.
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2. ประพันธ์ ภานุภาค, มนูญ ลีเชวงวงศ์, ทวีทรัพย์ ศิรประภาศิริ, วสันต์ จันทราทิตย์, วิชัย เตชะสาธิต, อัจฉรา ธีรรัตน์กุล, และคณะ, บรรณาธิการ. แนวทางการตรวจวินิจฉัยและการดูแลรักษาผู้ป่วยติดเชื้อเอชไอวีและผู้ป่วยเอดส์ระดับชาติ ปี พ.ศ.2553. ศูนย์พัฒนาระบบบริการยาต้านไวรัสสำหรับผู้ติดเชื้อเอชไอวีและผู้ป่วยเอดส์ในประเทศไทย; กันยายน 2553.
3. AIDSinfo. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Available from: URL: http://www.aidsinfo.nih.gov/Guidelines/HTML/2/ pediatric-treatment-guidelines/129/darunavir.
4. Mo H., Parkin N. Stewart,et al. Selection of resistance in protease inhibitor-experienced. J Virol 79: 3329-3338. Available from: URL:http://www/hivdb.stanford.edu/ pages/GRIP/LPV.html
5. Norton M, Young T, Parkin NT, Tokimoto D, Lu L , Piot-Matias T, et al. Prevalence mutational patterns and phenotypic correlates of the L76V protease mutation in relation to LPV-associated mutations, abstr. 854. Abstr. 15th Conf. Retrovir. Opportunistic Infect.
6. Kempf DJ, Isaacson JD, King MS, Brun SC, Xu Y, Real K,et al. Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients. J Virol 75: 7462-7469.
7. Vermeiren H, Van Craenenbroeck E, Alen P, Bacheler L, Picchio G, Lecocq P; Virco Clinical Response Collaborative Team. Prediction of HIV-1 drug susceptibility phenotype from the viral genotype using linear regression modeling. J Virol Methods 145: 47-55.
8. Delaugerre C, Flandre P, Chaix M, Dellamonica P, Raffi F, Jager H ,et al. Protease gene mutations in a trial comparing first-line lopinavir/ritonavir monotherapy to lopinavir/ritonavir + zidovudine/lamivudine (MONARK TRIAL) [abstract 75]. HIVDRW2007.
9. Nijhuis M, Wensing A, Bierman W, de Jong D, van Rooyen W, Katan R ,et al. A novel genetic pathway involving L76V and M46I leading to lopinavir/r resistance [abstract 127]. HIVDRW 2007.
10. Parkin NT, Chappey C, Petropoulos CJ. Improving lopinavir genotype algorithm through phenotype correlations: novel mutation patterns and amprenavir cross-resistance. AIDS 17: 955-961.
11. Prado JG, Wrin T, Beauchaine J, Ruiz L, Petropoulos CJ, Frost SD ,et al. Amprenavirresistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. AIDS 16: 1009-1017.
12. Garriga C, Perez-Elias MJ, Delgado R,et al. Mutational Patterns and correlated amino acid substitutions in the HIV-1protease after virological failure to nelfinavir-and lopinavir/ritonavir-based treatments.J Med Virol 2007 Nov; 79(11): 1617-28.
13. Victoria A. Johnson, MD, Vincent Calvez, MD, PhD, Huldrych F. Gunthard, MD . et al. Special Contribution 2011 Update of the Drug Resistance Mutations in HIV-1 Available from:URL:http://www.iasusa.org/resistance_mutations /mutations_figures.pdf
14. de Mendoza C, Valer L, Bacheler L,et al.Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance.AIDS. 2006 Apr 24; 20(7): 1071-4.
15. Kagan RM, Shenderovich MD, Heseltine PN, et al.Structural analysis of an HIV-1 protease I47A mutant resistant to the protease inhibitor lopinavir.Protein Sci. 2005 Jul; 14(7): 1870-8.
16. de Meyer S, Vangeneugden T, van Baelen B, de Paepe E, van Marck H, Picchio G et al. Resistance profile of darunavir: combined 24-week results from the POWER trials. AIDS Res. Hum. Retroviruses 24: 379-388.
17. de Mendoza C, Garrido C, Corral A, et al.Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance. AIDS. 2008 Jan 11; 22(2): 311-3.
18. Delaugerre C, Flandre P, Chaix ML ,et al. Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavirritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy. Antimicrob Agents Chemother. 2009 Jul; 53(7): 2934-9.
19. Bain-Brickley D, Butler LM, Kennedy GE, et al. Interventions to improve adherence to antiretroviral therapy in children with HIV infection. Cochrane Database Syst Rev. 2011 Dec 7; 12: CD009513.
20. Frange P, Briand N, Avettand-fenoel V,et al.Lopinavir/ritonavir-based antiretroviral therapy in human immunodeficiency virus type 1-infected naive children: rare protease inhibitor resistance mutations but high lamivudine/emtricitabine resistance at the time of virologic failure. Pediatr Infect Dis J. 2011; 30: 684-8.
21. Baras A, Champenois K, Choisy P, Yazdanpanah Y, Bocket L. Factors associated with the L76V protease mutation in HIV-1-infected patients with virological failure of lopinavir/ritonavir. Antivir. Ther. 14(Suppl.1): A114.
22. Delaugerre C, Flandre P, Chaix ML, Ghosn J, Raffi F, Dellamonica P, et al.Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavir-ritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy. Antimicrob. Agents Chemother. 53: 2934-2939.
23. Nijhuis M, Wensing AM, Bierman WF, de Jong D, Kagan R, Fun A, et al. Failure of treatment with first-line lopinavir boosted with ritonavir can be explained by novel resistance pathways with protease mutation 76V. J. Infect. Dis. 2009; 200: 698-709.
24 Lambert-Niclot S, Flandre P, Canestri A, Peytavin G, Blanc C, Agher R, et al. Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir. Antimicrob. Agents Chemother. 52: 491-496.
25. Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, et al. HIV-1 Protease Mutations and Protease Inhibitor Cross-Resistance. Antimicrob Agents Chemother. 2010, p. 4253-4261.
26. Braun P, Walter H, Hoffmann D, Da?umer M,Ehret R, Korn K, et al. Clinically relevant resensitization of protease inhibitors (PIs) saquinavir and atazanavir (ATV) by L76V mutation in multidrug-resistant HIV-1-infected patients. Antivir. Ther. 12: S142.
27. Mueller SM, Daeumer M, Kaiser R, Walter H, Colonno R., and Korn K. Susceptibility to saquinavir and atazanavir in highly protease inhibitor (PI) resistant HIV-1 is caused by lopinavir-induced drug resistance mutation L76V. Antivir. Ther. 9: S44.
28. Hall DB, Baxter JD, Schapiro JM, Boucher M, Clemens T and J. Scherer. 2008. Mutatins 24I, 50L/V, 54L, and 76V, selected by other protease inhibitors, predict durable response to tipranavir in treatment experienced patients when two or more are present. Antivir. Ther. 13(Suppl. 3): A136.
29. Tartaglia A, Saracino A, Monno L, Tinelli C, Angarano G. Both a protective and a deleterious role for the L76V mutation. Antimicrob. Agents Chemother. 53: 1724-1725.
30. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution. Prescribing information[online]. Available from:URL:http://www.kaletra.com [Accessed 2010 Jun22]
31. Young TP, Parkin NT, Stawiski E, et al.Prevalence, mutation patterns, and effects on protease inhibitor susceptibility of the L76V mutation in HIV-1 protease. Antimicrob Agents Chemother. 2010; 54: 4903-4906.
32. Sterrantino G, Zaccarelli M, Trotta M ,et al.Interpretation of Genotypic Resistance to Predict Darunavir/Ritonavir Failure in Antiretroviral Experienced Patients. J Acquir Immune Defic Syndr. 2012 Feb 1; 59(2): 170-172.
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