Correlates of nontransmission in US women at high risk of human immunodeficiency virus type 1 infection through sexual exposure.

Seventeen women who were persistently uninfected by human immunodeficiency virus type 1 (HIV-1), despite repeated sexual exposure, and 12 of their HIV-positive male partners were studied for antiviral correlates of non-transmission. Thirteen women had > or = 1 immune response in the form of CD8 cell noncytotoxic HIV-1 suppressive activity, proliferative CD4 cell response to HIV antigens, CD8 cell production of macrophage inflammatory protein-1 beta, or ELISPOT assay for HIV-1-specific interferon-gamma secretion. The male HIV-positive partners without AIDS had extremely high CD8 cell counts. All 8 male partners evaluated showed CD8 cell-related cytotoxic HIV suppressive activity. Reduced CD4 cell susceptibility to infection, neutralizing antibody, single-cell cytokine production, and local antibody in the women played no apparent protective role. These observations suggest that the primary protective factor is CD8 cell activity in both the HIV-positive donor and the HIV-negative partner. These findings have substantial implications for vaccine development.

[1]  R. Brookmeyer,et al.  Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda , 2001, The Lancet.

[2]  C. Kovacs,et al.  Factors contributing to the lack of human immunodeficiency virus type 1 (HIV-1) transmission in HIV-1-discordant partners. , 2000, The Journal of infectious diseases.

[3]  D. Burton,et al.  Absence of specific mucosal antibody responses in HIV-exposed uninfected sex workers from the Gambia , 2000, AIDS.

[4]  J. Mestecky,et al.  False positivity of enzyme-linked immunosorbent assay for measurement of secretory IgA antibodies directed at HIV type 1 antigens. , 2000, AIDS research and human retroviruses.

[5]  T. Quinn,et al.  Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. , 2000, The New England journal of medicine.

[6]  L. Lopalco,et al.  CCR5-Reactive Antibodies in Seronegative Partners of HIV-Seropositive Individuals Down-Modulate Surface CCR5 In Vivo and Neutralize the Infectivity of R5 Strains of HIV-1 In Vitro1 , 2000, The Journal of Immunology.

[7]  R. Kaul,et al.  HIV-1-Specific Mucosal CD8+ Lymphocyte Responses in the Cervix of HIV-1-Resistant Prostitutes in Nairobi1 , 2000, The Journal of Immunology.

[8]  J. T. Boerma,et al.  HIV incidence and HIV-associated mortality in a cohort of factory workers and their spouses in Tanzania, 1991 through 1996. , 2000 .

[9]  N. Sewankambo,et al.  Relative risks and population attributable fraction of incident HIV associated with symptoms of sexually transmitted diseases and treatable symptomatic sexually transmitted diseases in Rakai District, Uganda. Rakai Project Team. , 1999, AIDS.

[10]  L. Lopalco,et al.  Human immunodeficiency virus (HIV)-specific IgA and HIV neutralizing activity in the serum of exposed seronegative partners of HIV-seropositive persons. , 1999, The Journal of infectious diseases.

[11]  J. Margolick,et al.  High rates of transmission of subtype E human immunodeficiency virus type 1 among heterosexual couples in Northern Thailand: role of sexually transmitted diseases and immune compromise. , 1999, The Journal of infectious diseases.

[12]  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.

[13]  C. Tsoukas,et al.  Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocyte activity in HIV-exposed seronegative persons. , 1999, The Journal of infectious diseases.

[14]  M. Emerman,et al.  Protection against human immunodeficiency virus type 1 infection in persons with repeated exposure: evidence for T cell immunity in the absence of inherited CCR5 coreceptor defects. , 1999, The Journal of infectious diseases.

[15]  J. Skurnick,et al.  Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  John P. Moore,et al.  HIV–1 neutralizing antibodies: How full is the bottle? , 1999, Nature Medicine.

[17]  S. Rowland-Jones,et al.  A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. , 1999, Journal of immunology.

[18]  R. Kaul,et al.  HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers. , 1999, AIDS.

[19]  S. Rowland-Jones,et al.  Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. , 1998, The Journal of clinical investigation.

[20]  D B Louria,et al.  Herpes simplex type II and Mycoplasma genitalium as risk factors for heterosexual HIV transmission: report from the heterosexual HIV transmission study. , 1998, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[21]  J. Skurnick,et al.  Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  J. Skurnick,et al.  CD3+CD8+ cell levels as predictors of transmission in human immunodeficiency virus-infected couples: a report from the heterosexual HIV transmission study. , 1998, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[23]  Fred Russell Kramer,et al.  Spectral Genotyping of Human Alleles , 1998, Science.

[24]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.

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

[26]  M. Clerici,et al.  HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals , 1997, Nature Medicine.

[27]  D. Stram,et al.  Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients. Transfusion Safety Study Group. , 1997, American journal of epidemiology.

[28]  A. McMichael,et al.  Rapid Effector Function in CD8+ Memory T Cells , 1997, The Journal of experimental medicine.

[29]  B. Zerhouni.  HIV-specific cytotoxic T lymphocytes in persons exposed through sexual contact with HIV-infected patients. , 1997, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[30]  D. Katzenstein,et al.  A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137). , 1996, The Journal of infectious diseases.

[31]  J. Levy,et al.  Controlling HIV pathogenesis: the role of the noncytotoxic anti-HIV response of CD8+ T cells. , 1996, Immunology today.

[32]  Steven M. Wolinsky,et al.  Relative resistance to HIV–1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high–risk sexual exposures , 1996, Nature Medicine.

[33]  S. Arya,et al.  Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells , 1995, Science.

[34]  J. Spouge,et al.  Human plasma enhances the infectivity of primary human immunodeficiency virus type 1 isolates in peripheral blood mononuclear cells and monocyte-derived macrophages , 1995, Journal of virology.

[35]  J. Bartlett,et al.  IL‐7 enhancement of antigen‐driven activation/expansion of HIV‐1‐specific cytotoxic T lymphocyte precursors (CTLp) , 1995, Clinical and experimental immunology.

[36]  J. Berzofsky,et al.  ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. , 1995, The Journal of clinical investigation.

[37]  S. Rowland-Jones,et al.  Errata , 1995, Nature Medicine.

[38]  J. Callen.  A longitudinal study of human immunodeficiency virus transmission by heterosexual partners: de Vincenzi I for the European Study Group on Heterosexual Transmission of HIV. N Engl J Med 1994;331:341–346 , 1995 .

[39]  J. Lifson,et al.  Non-cytolytic CD8 T-cell anti-HIV responses in primary HIV-1 infection , 1994, The Lancet.

[40]  I. de Vincenzi,et al.  A Longitudinal Study of Human Immunodeficiency Virus Transmission by Heterosexual Partners , 1994 .

[41]  J. McElrath,et al.  Detection of rectal antibodies to HIV-1 by a sensitive chemiluminescent western blot immunodetection method. , 1994, Journal of acquired immune deficiency syndromes.

[42]  É. Oksenhendler,et al.  Human immunodeficiency virus (HIV) nef-specific cytotoxic T lymphocytes in noninfected heterosexual contact of HIV-infected patients. , 1994, The Journal of clinical investigation.

[43]  F. Valentine,et al.  Lymphocytes from some long-term seronegative heterosexual partners of HIV-infected individuals proliferate in response to HIV antigens. , 1992, AIDS research and human retroviruses.

[44]  E. G. Shpaer,et al.  Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro , 1992, Journal of virology.

[45]  J. Levy,et al.  Optimal conditions for recovery of the human immunodeficiency virus from peripheral blood mononuclear cells , 1988, Journal of clinical microbiology.

[46]  J. Levy,et al.  Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. , 1985, Virology.

[47]  J. Levy,et al.  Rapid CD8+ Cell Anti-HIV Activity Correlates with the Clinical State of the Infected Individual , 2003 .

[48]  J. Excler,et al.  Development and standardization of methods to evaluate the antibody response to an HIV-1 candidate vaccine in secretions and sera of seronegative vaccine recipients. , 1999, Journal of immunological methods.

[49]  M. Robb,et al.  Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand. Chiang Mai HEPS Working Group. , 1999, The Journal of infectious diseases.

[50]  S. Arya,et al.  Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. , 1995, Science.