Identification of new genotypic cut-off levels to predict the efficacy of lopinavir/ritonavir and darunavir/ritonavir in the TITAN trial

HIV Medicine

Volumn 10, Issue 10, 2009, Pages 620-626

  Hill, A ^a   Marcelin, A G ^b   Calvez, V ^b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b SORBONNE UNIVERSITÉ   (France)

Author keywords

Algorithms; Darunavir; Genotype; HIV RNA; Lopinavir; Resistance; Ritonavir

Indexed keywords

DARUNAVIR PLUS RITONAVIR; LOPINAVIR PLUS RITONAVIR;

ADULT; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; GENETIC ALGORITHM; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MALE; MULTIVARIATE LOGISTIC REGRESSION ANALYSIS; NONHUMAN; PREDICTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; VIRUS LOAD; VIRUS MUTATION; VIRUS RESISTANCE;

ADULT; ALGORITHMS; ANTI-HIV AGENTS; CD4 LYMPHOCYTE COUNT; DRUG RESISTANCE, VIRAL; DRUG THERAPY, COMBINATION; FEMALE; GENOTYPE; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; INTENTION TO TREAT ANALYSIS; LOGISTIC MODELS; MALE; MUTATION; PYRIMIDINONES; RITONAVIR; RNA, VIRAL; SENSITIVITY AND SPECIFICITY; SULFONAMIDES; TREATMENT OUTCOME; VIRAL LOAD;

EID: 70449363818     PISSN: 14642662     EISSN: 14681293     Source Type: Journal    
DOI: 10.1111/j.1468-1293.2009.00734.x     Document Type: Article

References (24)

1. Johnson V, Brun-Vezinet F, Clotet B. Update of the drug resistance mutations in HIV-1. Top HIV Med 2007, 15:119-125.
2. De Luca A, Antinori A, Di Giambenedetto S. Interpretation systems for genotypic drug resistance of HIV-1. Scand J Infect Dis 2003, 35((Suppl)):29-34.
3. King M, Rode R, Cohen-Codar I. Predictive genotypic algorithm for virologic response to lopinavir-ritonavir in protease inhibitor-experienced patients. Antimicrob Agents Chemother 2007, 51:3067-3074.
4. Calvez V, Masquelier B. http://www.hivfrenchresistance.org/2007/tab2.html, ANRS mutations list. Available at, (accessed 19 May 2008).
5. http://hivdb.stanford.edu, Stanford University. Stanford PI resistance algorithms. Available from, (accessed 19 May 2008).
6. Van Laetham K, De Luca A, Antinori A, Cingolani A, Perno C, Vandamme A. A genotypic drug resistance interpretation algorithm that significantly predicts therapy response in HIV-1-infected patients. Antivir Ther 2002, 7:123-129.
7. http://rxabbott.com/pdf/kaletratabpi.pdf, Abbott Pharmaceuticals. Lopinavir/ritonavir (Kaletra) US Prescribing Information. Abbott Laboratories, 2004. Available at, (accessed 19 May 2008).
8. Naeger L, Struble K. Effect of baseline protease genotype and phenotype on HIV response to atazanavir/ritonavir in treatment-experienced patients. AIDS 2006, 20:847-853.
9. Walmsley S, Cotte L, Rusconi S. Treatment response to ritonavir-boosted tipranavir vs. ritonavir-boosted lopinavir in HIV-1 patients with higher lopinavir mutation score. AIDS 2007, 21:2245-2248.
10. Kempf D, Isaacson J, King M. Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1 infected patients receiving lopinavir/ritonavir therapy. Antivir Ther 2002, 7:165-174.
11. http://www.fda.gov/CDER/GUIDANCE/3647fnl.pdf, US Department of Health and Human Services, Food and Drug Administration and Center for Drug Evaluation and Research. Guidance for industry: antiretroviral drugs using plasma HIV RNA measurements - clinical considerations for accelerated and traditional approval. Available at, (accessed 15 August 2007)
12. Hill A, Sabin C. Designing and interpreting HIV noninferiority trials in naïve and experienced patients. AIDS 2008, 22:913-921.
13. Walmsley S, Ruxrungtham K, Slim J, Ward D, Larson P, Raffi F. The Gemini Study. Saquinavir/r (SQV/r) . lopinavir/r (LPV/r) plus emtricitabine/tenofovir (FTC/TDF) as initial therapy in HIV-1-infected patients. . Madrid, Spain, October 2007 [Abstract PS1/4]
14. Eron J, Yeni P, Gathe J. The KLEAN study of fosamprenavir-ritonavir vs. lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks. Lancet 2006, 368:476-482.
15. Molina J, Andrade-Villanueva J, Echevarria J. Efficacy and safety of once-daily atazanavir-ritonavir compared to twice daily lopinavir-ritonavir, each in combination with tenofovir and emtricitabine in ARV-naïve HIV-1-infected subjects: the CASTLE Study, 48 week results. . Boston, MA, February 2008 [Abstract 37]
16. Ortiz R, DeJesus E, Khanlou H. Efficacy and safety of once-daily darunavir/ritonavir vs. lopinavir-ritonavir in treatment naïve HIV-1-infected patients at week 48. AIDS 2008, 22:1389-1397.
17. Hicks CB, Cahn P, Cooper DA. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies. Lancet 2006, 368:466-475.
18. Clotet B, Bellos N, Molina J. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2. Lancet 2007, 369:1169-1178.
19. Madruga J, Berger D, McMurchie M. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN. Lancet 2007, 370:49-58.
20. De Meyer S, Vangeneugden T, Lefebvre E. Phenotypic and genotypic determinants of TMC114 (darunavir) resistance: POWER 1, 2 and 3 pooled analysis. . Glasgow, UK, November 2006 [Abstract P196]
21. Johnson M, Grinsztejn B, Rodriguez C. Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures. AIDS 2005, 19:685-694.
22. Cooper D, Gatell J, Rockstroh J. Results of BENCHMRK-1, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. . Los Angeles, CA, February 2007 [Abstract 105aLB]
23. Madruga J, Cahn P, Grinsztejn B. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1. Lancet 2007, 370:29-38.
24. Lazzarin A, Campbell T, Clotet B. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2. Lancet 2007, 370:39-48.