A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia

James J. Goedert, Craig M. Kessler, Louis M. Aledort, Robert J. Biggar, W. Abe Andes, Gilbert C. White, James E. Drummond, Kampala Vaidya, Dean L. Mann, M. Elaine Eyster, Margaret V. Ragni, Michael M. Lederman, Alan R. Cohen, Gordon L. Bray, Philip S. Rosenberg, Robert M. Friedman, Margaret W. Hilgartner, William A. Blattner, Barbara Kroner, Mitchell H. Gail

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    Abstract

    We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (±SE) of 13.3±5.3 percent for ages 1 to 17, 26.8±6.4 percent for ages 18 to 34, and 43.7±16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P≤0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease. (N Engl J Med 1989; 321:1141–8.), ALTHOUGH the duration of infection with human immunodeficiency virus type 1 (HIV-1) is clearly related to the risk that the acquired immunodeficiency syndrome (AIDS) will develop, estimates of this risk have been imprecise because of the small numbers of subjects whose dates of HIV-1 seroconversion are known.1,2 Intermediate markers, particularly the numbers of circulating CD4+ T lymphocytes (CD4 counts), help to define prognoses, not only in persons with incident (i.e., dated) infections,2,3 but also in persons for whom the date of HIV-1 seroconversion cannot be ascertained.4 5 6 7 8 A refined quantification of the risk of AIDS, taking into consideration laboratory indexes and….

    Original languageEnglish (US)
    Pages (from-to)1141-1148
    Number of pages8
    JournalNew England Journal of Medicine
    Volume321
    Issue number17
    DOIs
    StatePublished - Oct 26 1989

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    Hemophilia A
    HIV-1
    Acquired Immunodeficiency Syndrome
    Prospective Studies
    Infection
    Incidence
    Lymphocyte Count
    HIV
    CD4 Lymphocyte Count
    Serum
    Interferons
    Biomarkers
    Seroconversion
    T-Lymphocytes
    Antigens

    All Science Journal Classification (ASJC) codes

    • Medicine(all)

    Cite this

    Goedert, J. J., Kessler, C. M., Aledort, L. M., Biggar, R. J., Andes, W. A., White, G. C., ... Gail, M. H. (1989). A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia. New England Journal of Medicine, 321(17), 1141-1148. https://doi.org/10.1056/NEJM198910263211701
    Goedert, James J. ; Kessler, Craig M. ; Aledort, Louis M. ; Biggar, Robert J. ; Andes, W. Abe ; White, Gilbert C. ; Drummond, James E. ; Vaidya, Kampala ; Mann, Dean L. ; Eyster, M. Elaine ; Ragni, Margaret V. ; Lederman, Michael M. ; Cohen, Alan R. ; Bray, Gordon L. ; Rosenberg, Philip S. ; Friedman, Robert M. ; Hilgartner, Margaret W. ; Blattner, William A. ; Kroner, Barbara ; Gail, Mitchell H. / A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia. In: New England Journal of Medicine. 1989 ; Vol. 321, No. 17. pp. 1141-1148.
    @article{826b9244d4e54534a9cf0cd8d5c01884,
    title = "A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia",
    abstract = "We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (±SE) of 13.3±5.3 percent for ages 1 to 17, 26.8±6.4 percent for ages 18 to 34, and 43.7±16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P≤0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease. (N Engl J Med 1989; 321:1141–8.), ALTHOUGH the duration of infection with human immunodeficiency virus type 1 (HIV-1) is clearly related to the risk that the acquired immunodeficiency syndrome (AIDS) will develop, estimates of this risk have been imprecise because of the small numbers of subjects whose dates of HIV-1 seroconversion are known.1,2 Intermediate markers, particularly the numbers of circulating CD4+ T lymphocytes (CD4 counts), help to define prognoses, not only in persons with incident (i.e., dated) infections,2,3 but also in persons for whom the date of HIV-1 seroconversion cannot be ascertained.4 5 6 7 8 A refined quantification of the risk of AIDS, taking into consideration laboratory indexes and….",
    author = "Goedert, {James J.} and Kessler, {Craig M.} and Aledort, {Louis M.} and Biggar, {Robert J.} and Andes, {W. Abe} and White, {Gilbert C.} and Drummond, {James E.} and Kampala Vaidya and Mann, {Dean L.} and Eyster, {M. Elaine} and Ragni, {Margaret V.} and Lederman, {Michael M.} and Cohen, {Alan R.} and Bray, {Gordon L.} and Rosenberg, {Philip S.} and Friedman, {Robert M.} and Hilgartner, {Margaret W.} and Blattner, {William A.} and Barbara Kroner and Gail, {Mitchell H.}",
    year = "1989",
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    language = "English (US)",
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    pages = "1141--1148",
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    Goedert, JJ, Kessler, CM, Aledort, LM, Biggar, RJ, Andes, WA, White, GC, Drummond, JE, Vaidya, K, Mann, DL, Eyster, ME, Ragni, MV, Lederman, MM, Cohen, AR, Bray, GL, Rosenberg, PS, Friedman, RM, Hilgartner, MW, Blattner, WA, Kroner, B & Gail, MH 1989, 'A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia', New England Journal of Medicine, vol. 321, no. 17, pp. 1141-1148. https://doi.org/10.1056/NEJM198910263211701

    A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia. / Goedert, James J.; Kessler, Craig M.; Aledort, Louis M.; Biggar, Robert J.; Andes, W. Abe; White, Gilbert C.; Drummond, James E.; Vaidya, Kampala; Mann, Dean L.; Eyster, M. Elaine; Ragni, Margaret V.; Lederman, Michael M.; Cohen, Alan R.; Bray, Gordon L.; Rosenberg, Philip S.; Friedman, Robert M.; Hilgartner, Margaret W.; Blattner, William A.; Kroner, Barbara; Gail, Mitchell H.

    In: New England Journal of Medicine, Vol. 321, No. 17, 26.10.1989, p. 1141-1148.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia

    AU - Goedert, James J.

    AU - Kessler, Craig M.

    AU - Aledort, Louis M.

    AU - Biggar, Robert J.

    AU - Andes, W. Abe

    AU - White, Gilbert C.

    AU - Drummond, James E.

    AU - Vaidya, Kampala

    AU - Mann, Dean L.

    AU - Eyster, M. Elaine

    AU - Ragni, Margaret V.

    AU - Lederman, Michael M.

    AU - Cohen, Alan R.

    AU - Bray, Gordon L.

    AU - Rosenberg, Philip S.

    AU - Friedman, Robert M.

    AU - Hilgartner, Margaret W.

    AU - Blattner, William A.

    AU - Kroner, Barbara

    AU - Gail, Mitchell H.

    PY - 1989/10/26

    Y1 - 1989/10/26

    N2 - We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (±SE) of 13.3±5.3 percent for ages 1 to 17, 26.8±6.4 percent for ages 18 to 34, and 43.7±16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P≤0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease. (N Engl J Med 1989; 321:1141–8.), ALTHOUGH the duration of infection with human immunodeficiency virus type 1 (HIV-1) is clearly related to the risk that the acquired immunodeficiency syndrome (AIDS) will develop, estimates of this risk have been imprecise because of the small numbers of subjects whose dates of HIV-1 seroconversion are known.1,2 Intermediate markers, particularly the numbers of circulating CD4+ T lymphocytes (CD4 counts), help to define prognoses, not only in persons with incident (i.e., dated) infections,2,3 but also in persons for whom the date of HIV-1 seroconversion cannot be ascertained.4 5 6 7 8 A refined quantification of the risk of AIDS, taking into consideration laboratory indexes and….

    AB - We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (±SE) of 13.3±5.3 percent for ages 1 to 17, 26.8±6.4 percent for ages 18 to 34, and 43.7±16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P≤0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease. (N Engl J Med 1989; 321:1141–8.), ALTHOUGH the duration of infection with human immunodeficiency virus type 1 (HIV-1) is clearly related to the risk that the acquired immunodeficiency syndrome (AIDS) will develop, estimates of this risk have been imprecise because of the small numbers of subjects whose dates of HIV-1 seroconversion are known.1,2 Intermediate markers, particularly the numbers of circulating CD4+ T lymphocytes (CD4 counts), help to define prognoses, not only in persons with incident (i.e., dated) infections,2,3 but also in persons for whom the date of HIV-1 seroconversion cannot be ascertained.4 5 6 7 8 A refined quantification of the risk of AIDS, taking into consideration laboratory indexes and….

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