Characterization of envelope glycoprotein gp41 genotype and phenotypic susceptibility to enfuvirtide at baseline and on treatment in the phase III clinical trials TORO-1 and TORO-2

AIDS Research and Human Retroviruses

Volumn 22, Issue 5, 2006, Pages 375-385

  Melby, T ^a   Sista, P ^b   DeMasi, R ^a   Kirkland, T ^a   Roberts, N ^c   Salgo, M ^d   Heilek Snyder, G ^c   Cammack, N ^c   Matthews, T J ^a   Greenberg, Michael L ^a,e  

^a Trimeris Pharmaceuticals   (United States)

^b BAYER CORPORATION   (United States)

^c Roche   (United States)

^d HOFFMANN LA ROCHE INC   (United States)

^e Trimeris Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; ENFUVIRTIDE; GLYCOPROTEIN GP 41; VIRUS GLYCOPROTEIN; VIRUS RNA;

ADOLESCENT; ADULT; AMINO ACID SEQUENCE; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG SENSITIVITY; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MUTAGENESIS; OPEN STUDY; PHASE 3 CLINICAL TRIAL; PHENOTYPE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TREATMENT OUTCOME; VIRUS ENVELOPE; VIRUS LOAD; VIRUS TYPING;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; DRUG RESISTANCE, VIRAL; GENOTYPE; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HUMANS; INHIBITORY CONCENTRATION 50; PHENOTYPE; POLYMORPHISM, GENETIC; TIME FACTORS;

EID: 33646868062     PISSN: 08892229     EISSN: None     Source Type: Journal    
DOI: 10.1089/aid.2006.22.375     Document Type: Article

References (51)

1. Richman D, Morton S, Wrin T, et al.: The prevalence of anti-retroviral drug resistance in the United States. AIDS 2004;18:1393-1401.
2. Wild C, Greenwell T, Shugars D, Rimsky-Clarke L, and Matthews T: The inhibitory activity of an HIV type 1 peptide correlates with itsability to interact with a leucine zipper structure. AIDS Res Hum Retroviruses 1995;11:323-325.
3. Wild C, Greenwell T, and Matthews TJ: A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 1993;9:1051-1053.
4. Rimsky LT, Shugars DC, and Matthews TJ: Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 1998;72:986-993.
5. Root MJ and Steger HK: HIV-1 gp41 as a target for viral entry inhibition. Curr Pharm Des 2004;10:1805-1825.
6. Church JA, Cunningham C, Hughes M, et al.: Safety and anti-retroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children. Pediatr Infect Dis J 2002;21:653-659.
7. Kilby JM, Hopkins S, Venetta TM, et al.: Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 1998;4:1302-1307.
8. Kilby JM, Lalezari JP, Eron JJ, et al.: The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res Hum Retroviruses 2002;18:685-693.
9. Lalezari JP, Eron JJ, Carlson M, et al.: A phase II clinical study of the long-term safety and antiviral activity of enfuvirtide-based antiretroviral therapy. AIDS 2003;17:691-698.
10. Wheeler DA, Lalezari JP, Kilby JM, et al.: Safety, tolerability, and plasma pharmacokinetics of high-strength formulations of enfuvirtide (T-20) in treatment-experienced HIV-1-infected patients. J Clin Virol 2004;30:183-190.
11. Lalezari JP, DeJesus E, Northfelt DW, et al.: A controlled phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther 2003;8:279-287.
12. Lalezari JP, Henry K, O'Hearn M, et al.: Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med 2003;348:2175-2185.
13. Lazzarin A, Clotet B, Cooper D, et al.: Efficacy of enfuvirtide in patients infected with drug-resistant human immunodeficiency virus type 1 in Europe and Australia. N Engl J Med 2003;348:2186-2195.
14. Katlama C, Arusteh K, Clotet B, Cooper D, et al.: Enfuvirtide TORO studies: 48 week results confirm 24 week findings. In: The 2nd IAS Conference on HIV Pathogenesis and Treatment. Paris, France, July 13-16, 2003; abstract LB2.
15. Fikkert V, Cherepanov P, Van LAetham K, et al.: Env chimeric virus technology for evaluating human immunodeficiency virus susceptibility to entry inhibitors. Antimicrob Agents Chemother 2002;46:3954-3962.
16. Wei X, Decker JM, Liu H, et al.: Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 2002;46:1896-1905.
17. Matthews T, Salgo M, Greenberg M, et al.: Enfuvirtide: The first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes. Nat Rev Drug Discov 2004;3:215-225.
18. Mink M, Greenberg ML, Mosier S, et al. Impact of HIV-1 gp41 amino acid substitutions (positions 36-45) on susceptibility to T-20 (enfuvirtide) in vitro: Analysis of primary virus isolates recovered from patients during chronic enfuvirtide treatment and site directed mutants in NL4-3. In: XIth International HIV Drug Resistance Workshop. Seville, Spain, July 2-5, 2002; abstract 22.
19. Sista PR, Melby T, Davison D, et al.: Characterization of determinants of genotypic and phenotypic resistance to enfuvirtide in baseline and on treatment HIV-1 isolates. AIDS 2004;18:1787-1794.
20. Sista P, Melby T, Greenberg ML, et al.: Characterization of baseline and treatment-emergent resistance to T-20 (enfuvirtide) observed in phase II clinical trials: Substitutions in gp41 amino acids 36-45 and enfuvirtide susceptibility of virus isolates. In: XIth International HIV Drug Resistance Workshop. Seville, Spain, July 2-5 2002; poster 21.
21. Lu J, Sista P, Giguel F, Greenberg ML, and Kuritzkes DR: Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). J Virol 2004;78:4628-4637.
22. DeGruttola V, Dix L, D'Aquila R, et al.: The relation between baseline HIV drug resistance and response to antiretroviral therapy: Re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antivir Ther 2000;5:41-48.
23. Huang W, Wrin T, Yap J, et al.: A rapid multi-functional HIV-1 entry assay for measuring drug susceptibility, co-receptor tropism, and antibody neutralization. In: 41st Interscience Conference on Antiviral Agents and Chemotherapy. Chicago, Illinois, December 16-19, 2001; abstract 1968.
24. Thompson JD, Higgins DG, and Gibson TJ. CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994;22:4673-4680.
25. Stanfield-Oakley SA, Jeffrey J, McDanal CB, et al.: Determinants of susceptibility to enfuvirtide map to gp41 in enfuvirtide-naive HIV-1. In: XIIth International HIV Drug Resistance Workshop. Los Cabos, Mexico, June 10-14, 2003; abstract 56.
26. Heil M, Decker J, Sfakianos J, et al.: Determinants of human immunodeficiency virus type 1 baseline susceptibility to fusion inhibitors enfuvirtide and T-649 reside outside the peptide interaction site. J Virol 2004;78:7582-7589.
27. Su C, Heilek-Snyder GFD, Ravindran P, et al.: The relationship between susceptibility to enfuvirtide of baseline viral recombinants and polymorphisms in the env region of R5-tropic HIV-1. In: XIIth International HIV Drug Resistance Workshop. Los Cabos, Mexico, June 10-14, 2003; abstract 54.
28. Greenberg ML, Melby T, Sista P, et al.: Baseline (BL) and on-treatment susceptibility to enfuvirtide seen in TORO 1 and TORO 2 through 24 weeks. In: 10th Conference on Retroviruses and Opportunistic Infections. Boston, Massachusetts, February 10-14, 2003; abstract 141.
29. Sista P, Melby T, Greenberg ML, et al.: Subgroup analysis of baseline (BL) susceptibility and early virological response to enfuvirtide in the combined TORO studies. In: XIIth International HIV Drug Resistance Workshop. Los Cabos, Mexico, June 10-14, 2003; abstract 55.
30. Labrosse B, Labernardiere JL, Dam E, et al.: Baseline susceptibility of primary human immunodeficiency virus type 1 to entry inhibitors. J Virol 2003;77:1610-1613.
31. Derdeyn CA, Decker JM, Sfakianos JN, et al.: Sensitivity of human immunodeficiency virus type 1 to fusion inhibitors targeted to the gp41 first heptad repeat involves distinct regions of gp41 and is consistently modulated by gp120 interactions with the coreceptor. J Virol 2001;75:8605-8614.
32. Derdeyn CA, Decker JM, Sfakianos JN, et al.: Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor t-20 is modulated by coreceptor specificity defined by the v3 loop of gp120. J Virol 2000;74:8358-8367.
33. Brumme ZL, Goodrich J, Mayer HB, Brumme CJ, Henrick BM, Wynhoven B, Asselin JJ, Cheung PK, Hogg RS, Montaner JS, and Harrigan PR: Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis 2005;192:466-474.
34. Moyle GJ, Wildfire A, Mandalia S, Mayer H, Goodrich J, Whitcomb J, and Gazzard BG: Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis 2005;191:866-872.
35. Reeves JD, Gallo SA, Ahmad N, Miamidian JL, Harvey PE, Sharron M, Pohlmann S, Sfakianos JN, Derdeyn CA, Blumenthal R, Hunter E, and Doms RW: Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci USA 2002;99:16249-16254.
36. Wrin T, Huang W, Yap J, Fransen S, Paxinos E, Parkin N, Whitcomb J, and Petropolous CJ: Evaluating HIV-1 coreceptor usage and inhibitors of virus entry using recombinant virus assays. In: 5th International Workshop on HIV Drug Resistance and Treatment Strategies. Scottsdale, Arizona, June 4-8, 2001.
37. Cilliers T, Patience T, Pillay C, Papathanasopoulos M, and Morris L: Sensitivity of HIV type 1 subtype C isolates to the entry inhibitor T-20. AIDS Res Hum Retroviruses 2004;20:477-482.
38. Aghokeng AF, Ewane L, Awazi B, Nanfack A, Delaporte E, Zekeng L, and Peeters M. Enfuvirtide binding domain is highly conserved in non-B HIV type 1 strains from Cameroon, West Central Africa. AIDS Res Hum Retroviruses 2005;21:430-433.
39. Brun-Vezinet F: Genetic pathways of resistance among HIV subtypes. In: 44th Interscience Conference on Antiviral Agents and Chemotherapy. Washington, D.C., October 30-November 2, 2004; abstract 1645.
40. Mink M, Mosier SM, Janumpalli S, et al.: Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol 2005;79:12447-12454.
41. Menzo S, Castagna A, Monachetti A, Hasson H, Danise A, Carini E, Bagnarelli P, Lazzarin A, and Clementi M: Genotype and phenotype patterns of human immunodeficiency virus type 1 resistance to enfuvirtide during long-term treatment. Antimicrob Agents Chemother 2004;48:3253-3259.
42. Xu L, Pozniak, A., Wildfire A, Stanfield-Oakley SA, Mosier SM, Ratcliffe D, Workman J, Joall A, Myers R, Smit E, Cane PA, Greenberg ML, and Pillay D: Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41. Antimicrob Agents Chemother 2005;49:1113-1119.
43. Melby T, DeMasi R, Miralles G, Heilek-Snyder G, and Greenberg ML: Evolution of enfuvirtide resistance in longitudinal samples obtained after continued enfuvirtide dosing post-virological failure. In: XIVth International Drug Resistance Workshop. Quebec City, PQ, Canada, June 7-11, 2005; abstract 67.
44. Su C, Heilek-Snyder G, Ravindran P, et al.: Substitutions within HIV gp41 amino acids 36-45 are identified as the primary determinants for loss of in vitro susceptibility to enfuvirtide: Results of data mining analyses of genotypic changes in gp41 in TORO 1 and TORO 2 that associate with changes in phenotypic susceptibility to enfuvirtide. In: XIIIth International HIV Drug Resistance Workshop. Tenerife, Spain, June 8-12, 2004; abstract 162.
45. Nameki D, Kodama E, Ikeuchi M, Mabuchi N, Otaka A, Tamamura H, Ohno M, Fujii N, and Matsuoka M: Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions. J Virol 2005;79:764-770
46. Delfraissy J-F, Montaner J, Eron J, et al.: Summary of pooled efficacy and safety analysis of enfuvirtide (ENF) treatment for 24 weeks in TORO 1 and TORO 2 phase III trials in highly anti-retroviral (ARV) treatment experienced patients. In: 10th Conference on Retroviruses and Opportunistic Infections. Boston, Massachusetts, February 10-14, 2003; abstract 568.
47. Walmsley S, Clotet B, Cooper D, et al.: Efficacy of enfuvirtide in subgroups of patients through 48 weeks of therapy in the TORO trials. In: 9th European AIDS Conference, Warsaw, Poland. October 25-29, 2003; poster 7.3/15.
48. Cohen C, DeMasi R, Greeberg ML, et al.: Selection of non-enfuvirtide (ENF) vs ENF-containing regimens leads to higher failure rates and loss of future antiretroviral (ARV) treatment options. In: 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Washington, D.C., October 30-November 2, 2004; poster H-580.
49. Clotet B, Raffi F, Cooper D, et al.: Clinical management of treatment-experienced, HIV infected patients with the fusion inhibitor enfuvirtide: Consensus recommendations. AIDS 2004;18:1137-1146.
50. Yeni PG, Hammer SM, Hirsch MS, et al.: Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA panel. JAMA 2004;292:251-265.
51. Pozniak A, Gazzard B, Anderson J, et al.: BHIVA Writing Committee on behalf of the British HIV Association (BHIVA): BHIVA guidelines for the treatment of HIV-infected adults with antiretroviral therapy. HIV Med 2003;4(Suppl. 1):1-41.