Treatment-mediated alterations in hiv fitness preserve CD4+ T cell counts but have minimal effects on viral load

PLoS Computational Biology

Volumn 6, Issue 11, 2010, Pages

  Vaidya, Naveen K ^a   Rong, Libin ^b   Marconi, Vincent C ^c   Kuritzkes, Daniel R ^d   Deeks, Steven G ^e,f   Perelson, Alan S ^a  

^a LOS ALAMOS NATIONAL LABORATORY   (United States)

^b OAKLAND UNIVERSITY   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f SAN FRANCISCO GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOLOGY; DISEASES; DRUG PRODUCTS; DRUG THERAPY; T-CELLS;

ANTIRETROVIRALS; BIOLOGICAL BASIS; CD4 T-CELLS; CELL COUNT; DRUG-RESISTANCE; INFECTED PATIENTS; MINIMAL EFFECTS; THERAPY CONTROL; VIRAL LOAD; VIRAL REPLICATION;

VIRUSES;

ANTIRETROVIRUS AGENT; ENFUVIRTIDE; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; VIRUS RNA; GLYCOPROTEIN GP 41; PEPTIDE FRAGMENT;

ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CASE REPORT; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CONCEPTUAL FRAMEWORK; CONTROLLED STUDY; DRUG WITHDRAWAL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MATHEMATICAL MODEL; VIROGENESIS; VIRUS LOAD; VIRUS RESISTANCE; BIOLOGICAL MODEL; DRUG EFFECT; HOST PATHOGEN INTERACTION; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; PHYSIOLOGY; PROGNOSIS; TREATMENT OUTCOME; VIROLOGY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; DRUG RESISTANCE, VIRAL; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMANS; MODELS, BIOLOGICAL; PEPTIDE FRAGMENTS; PROGNOSIS; TREATMENT OUTCOME; VIRAL LOAD;

EID: 78649669772     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1001012     Document Type: Article

References (36)

1. Lu J, Sista P, Giguel F, Greenberg M, Kuritzkes DR (2004) Relative replicative fitness of human immunodeficiency virus type 1 mutants resistant to enfuvirtide (T-20). J Virol 78: 4628-4637.
2. Miller MD (2004) K65R, TAMs and tenofovir. AIDS Rev 6: 22-33.
3. Nicastri E, Sarmati L, d'Ettorre G, Parisi SG, Palmisano L, et al. (2003) High prevalence of M184 mutation among patients with viroimmunologic discordantresponses to highly active antiretroviral therapy and outcomes after change of therapy guided by genotypic analysis. J Clin Microbiol 41: 3007-3012.
4. Sufka SA, Ferrari G, Gryszowka VE, Wrin T, Fiscus SA, et al. (2003) Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitorbased highly active antiretroviral therapy: immune response and viral control. J Infect Dis 187: 1027-1037.
5. Weber J, Chakraborty B, Weberova J, Miller MD, Quinones-Mateu ME (2005) Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. J Clin Microbiol 43: 1395-1400.
6. Reeves JD, Lee FH, Miamidian JL, Jabara CB, Juntilla MM, et al. (2005) Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization. J Virol 79: 4991-4999.
7. Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, et al. (1998) Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 4: 1302-1307.
8. Fung HB, Guo Y (2004) Enfuvirtide: a fusion inhibitor for the treatment of HIV infection. Clin Ther 26: 352-378.
9. Kitchen CM, Lu J, Suchard MA, Hoh R, Martin JN, et al. (2006) Continued evolution in gp41 after interruption of enfuvirtide in subjects with advanced HIV type 1 disease. AIDS Res Hum Retroviruses 22: 1260-1266.
10. Lazzarin A, Clotet B, Cooper D, Reynes J, Arasteh K, et al. (2003) Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 348: 2186-2195.
11. Deeks SG, Lu J, Hoh R, Neilands TB, Beatty G, et al. (2007) Interruption of enfuvirtide in HIV-1 infected adults with incomplete viral suppression on an enfuvirtide-based regimen. J Infect Dis 195: 387-391.
12. Lu J, Deeks SG, Hoh R, Beatty G, Kuritzkes BA, et al. (2006) Rapid emergence of enfuvirtide resistance in HIV-1-infected patients: results of a clonal analysis. J Acquir Immune Defic Syndr 43: 60-64.
13. Marconi V, Bonhoeffer S, Paredes R, Lu J, Hoh R, et al. (2008) Viral dynamics and in vivo fitness of HIV-1 in the presence and absence of enfuvirtide. J Acquir Immune Defic Syndr 48: 572-576.
14. Greenberg ML, Cammack N (2004) Resistance to enfuvirtide, the first HIV fusion inhibitor. J Antimicrob Chemother 54: 333-340.
15. Marcelin AG, Reynes J, Yerly S, Ktorza N, Segondy M, et al. (2004) Characterization of genotypic determinants in HR-1 and HR-2 gp41 domains in individuals with persistent HIV viraemia under T-20. AIDS 18: 1340-1342.
16. Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, et al. (2005) 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 79: 12447-12454.
17. Poveda E, Rodes B, Lebel-Binay S, Faudon JL, Jimenez V, et al. (2005) Dynamics of enfuvirtide resistance in HIV-infected patients during and after long-term enfuvirtide salvage therapy. J Clin Virol 34: 295-301.
18. Aquaro S, D'Arrigo R, Svicher V, Perri GD, Caputo SL, et al. (2006) Specific mutations in HIV-1 gp41 are associated with immunological success in HIV-1- infected patients receiving enfuvirtide treatment. J Antimicrob Chemother 58: 714-722.
19. Xu L, Pozniak A, Wildfire A, Stanfield-Oakley SA, Mosier SM, et al. (2005) Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41. Antimicrob Agents Chemother 49: 1113-1119.
20. McLean AR, Nowak MA (1992) Competition between zidovudine-sensitive and zidovudine-resistant strains of HIV. AIDS 6: 71-79.
21. Rong L, Feng Z, Perelson AS (2007) Emergence of HIV-1 drug resistance during antiretroviral treatment. Bull Math Biol 69: 2027-2060.
22. Sachsenberg N, Perelson AS, Yerly S, Schockmel GA, Leduc D, et al. (1998) Turnover of CD4+ and CD8+ T lymphocytes in HIV-1 infection as measured by Ki-67 antigen. J Exp Med 187: 1295-1303.
23. Nowak MA, May RM (2000) Virus dynamics: mathematical principles of immunology and virology. New York: Oxford University Press Inc.
24. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271: 1582-1586.
25. Ramratnam B, Bonhoeffer S, Binley J, Hurley A, Zhang L, et al. (1999) Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354: 1782-1785.
26. Mohri H, Bonhoeffer S, Monard S, Perelson AS, Ho DD (1998) Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 279: 1223-1227.
27. Tuckwell HC, Shipman PD, Perelson AS (2008) The probability of HIV infection in a new host and its reduction with microbicides. Math Biosci 214: 81-86.
28. Macey RI, Oster GF (2001) Berkeley Madonna, version 8.3.18. Berkeley, CA: University of California at Berkeley.
29. Efron B, Tibshirani R (1986) Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci 1: 54-75.
30. Stafford MA, Corey L, Cao Y, Daar ES, Ho DD, et al. (2000) Modeling plasma virus concentration during primary HIV infection. J Theor Biol 203: 285-301.
31. Markowitz M, Louie M, Hurley A, Sun E, Di Mascio M, et al. (2003) A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol 77: 5037-5038.
32. Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, et al. (1996) Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci U S A 93: 4398-4402.
33. Derdeyn CA, Kilby JM, Miralles GD, Li LF, Sfakianos G, et al. (1999) Evaluation of distinct blood lymphocyte populations in human immunodeficiency virus type 1-infected subjects in the absence or presence of effective therapy. J Infect Dis 180: 1851-1862.
34. Lambotte O, Chaix ML, Gubler B, Nasreddine N, Wallon C, et al. (2004) The lymphocyte HIV reservoir in patients on long-term HAART is a memory of virus evolution. AIDS 18: 1147-1158.
35. Poveda E, Rodes B, Labernardiere JL, Benito JM, Toro C, et al. (2004) Evolution of genotypic and phenotypic resistance to Enfuvirtide in HIV-infected patients experiencing prolonged virologic failure. J Med Virol 74: 21-28.
36. Murray JD, Perelson AS (2005) Human immunodeficiency virus: Quasispecies and drug resistance. Multiscale Model Simul 3: 300-311.