Past, present and future: 30 years of HIV research

This year marks the thirtieth anniversary of the publication of the study that first reported the isolation of HIV-1. In this Timeline article, we provide a historical perspective of some of the major milestones in HIV science, highlighting how translational research has affected treatment and prevention of HIV. Finally, we discuss some of the current research directions and the scientific challenges ahead, in particular in the search for a cure for HIV.

[1]  J. Kublin,et al.  Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. , 2011, The Lancet. Infectious diseases.

[2]  J. Chermann,et al.  Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). , 1983, Science.

[3]  M. Martin,et al.  Molecular organization of the AIDS retrovirus , 1985, Cell.

[4]  W. Saurin,et al.  The evolutionary rate of nonpathogenic simian immunodeficiency virus (SIVagm) is in agreement with a rapid and continuous replication in vivo. , 1996, Virology.

[5]  M A Fischl,et al.  A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. , 1997, The New England journal of medicine.

[6]  Christine Hogan,et al.  Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract , 2004, The Journal of experimental medicine.

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

[8]  Katrien Fransen,et al.  Preexposure prophylaxis for HIV infection among African women. , 2012, The New England journal of medicine.

[9]  M A Fischl,et al.  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[10]  Pham Phung,et al.  Broad neutralization coverage of HIV by multiple highly potent antibodies , 2011, Nature.

[11]  P. Bieniasz,et al.  Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu , 2008, Nature.

[12]  Lynn Morris,et al.  Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women , 2010, Science.

[13]  M. Peeters,et al.  Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. , 1989, AIDS.

[14]  髙折 晃史,et al.  19th Conference on Retroviruses and Opportunistic Infections , 2012 .

[15]  Marc C. Johnson,et al.  The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. , 2008, Cell host & microbe.

[16]  J. Chermann,et al.  Molecular cloning of lymphadenopathy-associated virus , 1984, Nature.

[17]  K. Steimer,et al.  Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). , 1985, Science.

[18]  M. Greaves,et al.  The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus , 1984, Nature.

[19]  Mario Roederer,et al.  HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. , 2006, Blood.

[20]  Robin A. Weiss,et al.  The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain , 1986, Cell.

[21]  A MarioCalvo,et al.  Vaccination with ALVAC and AIDS-VAX to prevent HIV-1 infection in Thailand , 2010 .

[22]  Devan V Mehrotra,et al.  Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial , 2008, The Lancet.

[23]  D W Barry,et al.  3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Martin A. Nowak,et al.  Antibody neutralization and escape by HIV-1 , 2003, Nature.

[25]  Cheryl Jennings,et al.  Depletion of latent HIV-1 infection in vivo: a proof-of-concept study , 2005, The Lancet.

[26]  Till Bärnighausen,et al.  Increases in Adult Life Expectancy in Rural South Africa: Valuing the Scale-Up of HIV Treatment , 2013, Science.

[27]  Asier Sáez-Cirión,et al.  HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype , 2007, Proceedings of the National Academy of Sciences.

[28]  A. Krishnan,et al.  Plasma Viremia and Cellular HIV-1 DNA Persist Despite Autologous Hematopoietic Stem Cell Transplantation for HIV-Related Lymphoma , 2013, Journal of acquired immune deficiency syndromes.

[29]  R. Weiss.  Thirty years on: HIV receptor gymnastics and the prevention of infection , 2013, BMC Biology.

[30]  J J Goedert,et al.  Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene , 1996, Science.

[31]  Philip R. Johnson,et al.  An African primate lentivirus (SIVsmclosely related to HIV-2 , 1989, Nature.

[32]  Tongqing Zhou,et al.  Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01 , 2010, Science.

[33]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[34]  C. Rinaldo,et al.  High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors , 1995, Journal of virology.

[35]  David V Glidden,et al.  Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. , 2010, The New England journal of medicine.

[36]  Marc Parmentier,et al.  Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene , 1996, Nature.

[37]  D. Ho,et al.  Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. , 1995, The New England journal of medicine.

[38]  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.

[39]  R. Gelber,et al.  "Reduction of Maternal-Infant Transmission of Human Immunodeficiency Virus Type I with Zidovudine Treatment." , 1994 .

[40]  Todd M. Allen,et al.  HIV-1 adaptation to NK cell mediated immune pressure , 2011, Nature.

[41]  J. Brenchley,et al.  Microbial translocation is a cause of systemic immune activation in chronic HIV infection , 2006, Retrovirology.

[42]  B. Sobhian,et al.  SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx , 2011, Nature.

[43]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[44]  D. Price,et al.  CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract , 2004, The Journal of experimental medicine.

[45]  Robert F. Siliciano,et al.  In vivo fate of HIV-1-infected T cells: Quantitative analysis of the transition to stable latency , 1995, Nature Medicine.

[46]  Luc Montagnier,et al.  T-lymphocyte T4 molecule behaves as the receptor for human retrovirus  LAV , 1984, Nature.

[47]  Stephen Moses,et al.  Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial , 2007, The Lancet.

[48]  M. Gottlieb,et al.  Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. , 1981, The New England journal of medicine.

[49]  Paul E. Kennedy,et al.  HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor , 1996, Science.

[50]  Richard A Koup,et al.  Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection , 1996, Cell.

[51]  M A Fischl,et al.  The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[52]  E. Thiel,et al.  Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. , 2009, The New England journal of medicine.

[53]  Oliver Laeyendecker,et al.  Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial , 2007, The Lancet.

[54]  Michael Rayment,et al.  Prevention of HIV-1 infection with early antiretroviral therapy , 2012, Journal of Family Planning and Reproductive Health Care.

[55]  Brigitte Autran,et al.  Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study , 2013, PLoS pathogens.

[56]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[57]  Robert S. Pinals,et al.  A double‐blind, placebo‐controlled trial , 1986 .

[58]  M. Malim,et al.  Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein , 2002, Nature.

[59]  Jerome H. Kim,et al.  Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. , 2009, The New England journal of medicine.

[60]  A. Fauci,et al.  Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. , 1983, The New England journal of medicine.

[61]  Keith Hoots,et al.  Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS , 2002, Nature Genetics.

[62]  F. Marincola,et al.  HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[63]  J. Levy,et al.  Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. , 1984, Science.

[64]  Ron Diskin,et al.  HIV therapy by a combination of broadly neutralizing antibodies in humanized mice , 2012, Nature.

[65]  C. Rouzioux,et al.  HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[66]  M. Carrington,et al.  Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV‐1 infection , 1998, AIDS.

[67]  C. M. Owens,et al.  The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys , 2004, Nature.

[68]  S. J. Clark,et al.  High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. , 1993, Science.

[69]  S. Buchbinder,et al.  Long‐term HIV‐1 infection without immunologic progression , 1994, AIDS.

[70]  F. Brun-Vézinet,et al.  DETECTION OF IgG ANTIBODIES TO LYMPHADENOPATHY-ASSOCIATED VIRUS IN PATIENTS WITH AIDS OR LYMPHADENOPATHY SYNDROME , 1984, The Lancet.

[71]  R. Gallo,et al.  Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. , 1984, Science.

[72]  J Schüpbach,et al.  Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. , 1984, Science.

[73]  D. Douek,et al.  Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts , 2009, Nature Medicine.

[74]  L. Montagnier,et al.  Simian Immunodeficiency Virus Replicates to High Levels in Sooty Mangabeys without Inducing Disease , 1998, Journal of Virology.

[75]  R P Johnson,et al.  Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. , 1998, Science.

[76]  Olivier Danos,et al.  Nucleotide sequence of the AIDS virus, LAV , 1985, Cell.

[77]  Q. Sattentau,et al.  Anti-HIV IgA isotypes: differential virion capture and inhibition of transcytosis are linked to prevention of mucosal R5 SHIV transmission , 2013, AIDS.

[78]  J. Sodroski,et al.  Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody , 1998, Nature.

[79]  Emmanuel Lagarde,et al.  Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial , 2005, PLoS medicine.

[80]  G. Shaw,et al.  Molecular cloning and characterization of the HTLV-III virus associated with AIDS , 1984, Nature.

[81]  Anthony S. Fauci,et al.  HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease , 1993, Nature.

[82]  S. J. Potter,et al.  Molecular cloning of AIDS-associated retrovirus , 1984, Nature.

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

[84]  Mario Roederer,et al.  Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection , 2005, Nature.

[85]  Mario Roederer,et al.  Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 , 2010, Science.