HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy.

Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to suppression of HIV-1 plasma viremia to undetectable levels for 3 or more years. However, adherence to complex drug regimens can prove problematic, and subjects may temporarily discontinue HAART for variable periods. We studied 6 HIV-1-infected individuals who stopped therapy. Off HAART, levels of viremia were suppressed to fewer than 500 copies/mL in 2 subjects for more than 12 and more than 24 months, respectively, and in 1 subject for 4 months on 1 occasion. Three subjects failed to contain plasma viremia. Broad and strong HIV-1-specific immune responses were detected in subjects with prolonged suppression of viral replication. This longitudinal study suggests that containment of HIV-1 replication to low or undetectable levels after discontinuation of HAART is associated with strong virus-specific immune responses. Boosting of HIV-1-specific immune responses should be considered as an adjunctive treatment strategy for HIV-1-infected individuals on HAART.

[1]  G. Shaw,et al.  Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection , 1994, Journal of virology.

[2]  D. Ho,et al.  Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome , 1994, Journal of virology.

[3]  A. Trkola,et al.  Restricted antigenic variability of the epitope recognized by the neutralizing gp41 antibody 2F5 , 1996, AIDS.

[4]  J. Goedert,et al.  Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. , 1996, JAMA.

[5]  John W. Mellors,et al.  Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma , 1996, Science.

[6]  D. Ho,et al.  Characterization of long-term survivors of human immunodeficiency virus type 1 infection. , 1996, Immunology letters.

[7]  R Brookmeyer,et al.  Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. , 1997, Science.

[8]  P. Klenerman,et al.  Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Xiping Wei,et al.  Antiviral pressure exerted by HIV-l-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus , 1997, Nature Medicine.

[10]  J. Seigneurin,et al.  Absence of viral rebound after treatment of HIV-infected patients with didanosine and hydroxycarbamide , 1997, The Lancet.

[11]  D. Richman,et al.  Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. , 1997, Science.

[12]  M A Nowak,et al.  Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  E. Rosenberg,et al.  Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. , 1997, Science.

[14]  C. Rouzioux,et al.  High rebound of plasma and cellular HIV load after discontinuation of triple combination therapy. , 1998, AIDS.

[15]  J. Altman,et al.  Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function , 1998, The Journal of experimental medicine.

[16]  D. Ho,et al.  HIV-1 Antigen–specific and –nonspecific B Cell Responses Are Sensitive to Combination Antiretroviral Therapy , 1998, The Journal of experimental medicine.

[17]  Antiretroviral therapy in countries with low health expenditure , 1998, The Lancet.

[18]  M A Nowak,et al.  Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. , 1998, Science.

[19]  B. Walker,et al.  Longitudinal and Cross-Sectional Analysis of Cytotoxic T Lymphocyte (CTL) Responses and their Relationship to Vertical HIV Transmission , 1998 .

[20]  B. Walker,et al.  Longitudinal and cross-sectional analysis of cytotoxic T lymphocyte responses and their relationship to vertical human immunodeficiency virus transmission. ARIEL Project Investigators. , 1998, The Journal of infectious diseases.

[21]  Studies reveal early impact of HIV infection, effects of treatment. , 1998, JAMA.

[22]  A. Trkola,et al.  Immunological and Virological Analyses of Persons Infected by Human Immunodeficiency Virus Type 1 while Participating in Trials of Recombinant gp120 Subunit Vaccines , 1998, Journal of Virology.

[23]  C. Sabin,et al.  Rebound of HIV-1 viral load after suppression to very low levels. , 1998, AIDS.

[24]  J. Lisziewicz,et al.  HIV-1 suppression by early treatment with hydroxyurea, didanosine, and a protease inhibitor , 1998, The Lancet.

[25]  S. Staszewski,et al.  HIV‐1 RNA, CD4 cell count and the risk of progression to AIDS and death during treatment with HIV‐1 reverse transcriptase inhibitors , 1998, AIDS.

[26]  J. Stephenson.  AIDS researchers target poor adherence. , 1999, JAMA.

[27]  R. Steinman,et al.  A recombinant vaccinia virus based ELISPOT assay detects high frequencies of Pol-specific CD8 T cells in HIV-1-positive individuals. , 1999, AIDS.

[28]  A. Perelson,et al.  Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. , 1999, The New England journal of medicine.

[29]  J. Lisziewicz,et al.  Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy , 1999, Nature Medicine.

[30]  J. Moore,et al.  The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses. , 1999, The Journal of infectious diseases.

[31]  D. Ho,et al.  Molecular tracking of an Human Immunodeficiency Virus nef specific cytotoxic T-cell clone shows persistence of clone-specific T-cell receptor DNA but not mRNA following early combination antiretroviral therapy. , 1999, Immunology letters.

[32]  C. A. Macken,et al.  Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. , 1999, The New England journal of medicine.

[33]  M. Nowak,et al.  Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy , 1999, Journal of Virology.

[34]  T. Merigan,et al.  Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART). , 1999, Journal of immunology.