Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Less is more? STI in acute and chronic HIV-1 infection

Emerging data has indicated that supervised treatment interruption (STI) of highly active antiretroviral therapy might significantly augment immune responses in HIV-1-infected patients and slow disease progression. Here the authors discuss the rationale behind STI and future directions for study.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Enhancement of virus-specific immune responses by STI.

References

  1. Dybul, M. et al. Short-cycle intermittent HAART: A pilot study. in Program and Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections, Abstract 354 (Chicago, Illinois, 2001).

    Google Scholar 

  2. Miller, V. Structured treatment interruptions in antiretroviral management of HIV- 1. Curr. Opin. Infect. Dis. 14, 29–37 (2001).

    Article  Google Scholar 

  3. Miller, V. et al. Virological and immunological effects of treatment interruptions in HIV- 1 infected patients with treatment failure. AIDS 14, 2857–2867 (2000).

    Article  CAS  Google Scholar 

  4. Deeks, S.G. et al. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N. Engl. J. Med. 344, 472–480 (2001).

    Article  CAS  Google Scholar 

  5. Autran, B. et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 277, 112–116 (1997).

    Article  CAS  Google Scholar 

  6. Rosenberg, E.S. et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447–1450 (1997).

    Article  CAS  Google Scholar 

  7. Lisziewicz, J. et al. Control of HIV despite the discontinuation of antiretroviral therapy. N. Engl. J. Med. 340, 1683–1684 (1999).

    Article  CAS  Google Scholar 

  8. Ortiz, G.M. et al. HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy. J. Clin. Invest. 104, R13–18 (1999).

    Article  CAS  Google Scholar 

  9. Goulder, P.J.R., Rowland, S.L., McMichael, A.J. & Walker, B.D. Anti-HIV cellular immunity: recent advances towards vaccine design. AIDS 13, s121–s136 (1999).

    CAS  PubMed  Google Scholar 

  10. McMichael, A.J. & Rowland-Jones, S.L. Cellular immune responses to HIV. Nature 410, 980–987 (2001).

    Article  CAS  Google Scholar 

  11. Schmitz, J.E. et al. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283, 857–860 (1999).

    Article  CAS  Google Scholar 

  12. Jin, X. et al. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189, 991–998 (1999).

    Article  CAS  Google Scholar 

  13. Ogg, G.S. et al. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279, 2103–2106 (1998).

    Article  CAS  Google Scholar 

  14. Kalams, S.A. et al. Association between virus-specific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection. J. Virol. 73, 6715–6720 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Poignard, P. et al. Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo. Immunity 10, 431–438 (1999).

    Article  CAS  Google Scholar 

  16. Harrer, T. et al. Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. J. Immunol. 156, 2616–2623 (1996).

    CAS  PubMed  Google Scholar 

  17. Harrer, T. et al. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of people with stable nonprogressing HIV type 1 infection. AIDS Res. Hum. Retroviruses 12, 585–592 (1996).

    Article  CAS  Google Scholar 

  18. Oxenius, A. et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc. Natl. Acad. Sci. USA 97, 3382–3387 (2000).

    Article  CAS  Google Scholar 

  19. Malhotra, U. et al. Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection. J. Infect. Dis. 181, 121–131 (2000).

    Article  CAS  Google Scholar 

  20. Altfeld, M. et al. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J. Exp. Med. 193, 169–180 (2001).

    Article  CAS  Google Scholar 

  21. Rosenberg, E.S. et al. Immune control of HIV-1 after early treatment of acute infection. Nature 407, 523–526 (2000).

    Article  CAS  Google Scholar 

  22. Hermans, P. et al. Successful interruption of antiretroviral therapy (ARVT) in patients with primary HIV infection (PHI). in Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections Abstract 290 (Chicago, Illinois, 2001).

    Google Scholar 

  23. Markowitz, M. et al. Prolonged HAART initiated within 120 days of primary HIV-1 infection does not result in sustained control of HIV-1 after cessation of therapy. in Program and abstracts of the 8th Conference on Retroviruses and Opportunistic Infections Abstract 288 (Chicago, Illinois, 2001).

    Google Scholar 

  24. Blankson, J.N., Gallant, J.E. & Siliciano, R.F. Proliferative responses to human immunodeficiency virus type 1 (HIV-1) antigens in HIV-1-infected patients with immune reconstitution. J. Infect. Dis. 183, 657–661 (2001).

    Article  CAS  Google Scholar 

  25. Lori, F. et al. Hydroxyurea and didanosine long-term treatment prevents HIV breakthrough and normalizes immune parameters. AIDS Res. Hum. Retroviruses 15, 1333–1338 (1999).

    Article  CAS  Google Scholar 

  26. Montaner, L.J. Structured treatment interruptions to control HIV-1 and limit drug exposure. Trends Immunol. 22, 92–96 (2001).

    Article  CAS  Google Scholar 

  27. Garcia, F. et al. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS 13, F79–86 (1999).

    Article  CAS  Google Scholar 

  28. Ruiz, L. et al. Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. AIDS 14, 397–403 (2000).

    Article  CAS  Google Scholar 

  29. Neumann, A.U. et al. HIV-1 rebound during interruption of highly active antiretroviral therapy has no deleterious effect on reinitiated treatment. Comet Study Group. AIDS 13, 677–683 (1999).

    Article  CAS  Google Scholar 

  30. Davey, R.T. Jr et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. USA 96, 15109–15114 (1999).

    Article  CAS  Google Scholar 

  31. Papasavvas, E. et al. Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected people after temporary treatment interruption. J. Infect. Dis. 182, 766–775 (2000).

    Article  CAS  Google Scholar 

  32. Hatano, H. et al. Pre-HAART HIV burden approximates post-HAART viral levels following interruption of therapy in patients with sustained viral suppression. AIDS 14, 1357–1363 (2000).

    Article  CAS  Google Scholar 

  33. Colven, R., Harrington, R.D., Spach, D.H., Cohen, C.J. & Hooton, T.M. Retroviral rebound syndrome after cessation of suppressive antiretroviral therapy in three patients with chronic HIV infection. Ann. Intern. Med. 133, 430–434 (2000).

    Article  CAS  Google Scholar 

  34. Kilby, J.M. et al. Recurrence of the acute HIV syndrome after interruption of antiretroviral therapy in a patient with chronic HIV infection: A case report. Ann. Intern. Med. 133, 435–438 (2000).

    Article  CAS  Google Scholar 

  35. Ruiz, L. et al. HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection. AIDS 15, F19–27 (2001).

    Article  CAS  Google Scholar 

  36. Garcia, F. et al. The virological and immunological consequences of structured treatment interruptions in chronic HIV-1 infection. AIDS 15, F29–40 (2001).

    Article  CAS  Google Scholar 

  37. Zajac, A.J. et al. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med. 188, 2205–2213 (1998).

    Article  CAS  Google Scholar 

  38. Altfeld, M. & Rosenberg, E.S. The role of CD4(+) T helper cells in the cytotoxic T lymphocyte response to HIV-1. Curr. Opin. Immunol. 12, 375–380 (2000).

    Article  CAS  Google Scholar 

  39. Walker, B.D. & Korber, B.T. Immune control of HIV: the obstacles of HLA and viral diversity. Nature Immunol. 2, 473–475 (2001).

    Article  CAS  Google Scholar 

  40. Migueles, S.A. et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc. Natl. Acad. Sci. USA 97, 2709–2714 (2000).

    Article  CAS  Google Scholar 

  41. Goulder, P.J.R. et al. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature (in the press).

  42. Goulder, P.J. et al. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nature Med. 3, 212–217 (1997).

    Article  CAS  Google Scholar 

  43. Carrington, M. et al. HLA and HIV-1: Heterozygote advantage and B*35-Cw*04 disadvantage. Science 283, 1748–1752 (1999).

    Article  CAS  Google Scholar 

  44. Flores-Villanueva, P.O. et al. Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity. Proc. Natl. Acad. Sci. USA 98, 5140–5145 (2001).

    Article  CAS  Google Scholar 

  45. Barouch, D.H. et al. Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290, 486–492 (2000).

    Article  CAS  Google Scholar 

  46. Amara, R.R. et al. Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292, 69–74 (2001).

    Article  CAS  Google Scholar 

  47. Bhardwaj, N. et al. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells. J. Clin. Invest. 94, 797–807 (1994).

    Article  CAS  Google Scholar 

  48. Sarawar, S.R., Lee, B.J., Reiter, S.K. & Schoenberger, S.P. Stimulation via CD40 can substitute for CD4 T cell function in preventing reactivation of a latent herpesvirus. Proc. Natl. Acad. Sci. USA 98, 6325–6329 (2001).

    Article  CAS  Google Scholar 

  49. Ostrowski, M.A. et al. The role of CD4(+) T cell help and CD40 ligand in the In vitro expansion of HIV-1-specific memory cytotoxic CD8(+) T cell responses. J. Immunol. 165, 6133–6141 (2000).

    Article  CAS  Google Scholar 

  50. Day, C.L. et al. Relative dominance of epitope-specific cytotoxic t-lymphocyte responses in human immunodeficiency virus type 1-infected people with shared hla alleles. J. Virol. 75, 6279–6291 (2001).

    Article  CAS  Google Scholar 

  51. Lori, F. et al. Control of SIV rebound through structured treatment interruptions during early infection. Science 290, 1591–1593 (2000).

    Article  CAS  Google Scholar 

  52. Hel, Z. et al. Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques. Nature Med. 6, 1140–1146 (2000).

    Article  CAS  Google Scholar 

  53. Lyles, R.H. et al. Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study. J. Infect. Dis. 181, 872–880 (2000).

    Article  CAS  Google Scholar 

  54. Volberding, P.A. et al. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in people with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N. Engl. J. Med. 322, 941–949 (1990).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Altfeld, M., Walker, B. Less is more? STI in acute and chronic HIV-1 infection. Nat Med 7, 881–884 (2001). https://doi.org/10.1038/90901

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/90901

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing