Thromb Haemost 1991; 66(04): 415-419
DOI: 10.1055/s-0038-1646430
Review Article
Schattauer GmbH Stuttgart

CD4 Cells in HIV-1 Infected Hemophiliacs: Effect of Factor VIII Concentrates

JoAnne M Goldsmith
1   The Section of Infectious Disease, Northwestern University Medical School and Rehabilitation Institute of Chicago, IL, USA
,
Joann Deutsche
1   The Section of Infectious Disease, Northwestern University Medical School and Rehabilitation Institute of Chicago, IL, USA
2   Hematology-Oncology, Northwestern University Medical School and Rehabilitation Institute of Chicago, IL, USA
,
Mary Tang
2   Hematology-Oncology, Northwestern University Medical School and Rehabilitation Institute of Chicago, IL, USA
,
David Green
2   Hematology-Oncology, Northwestern University Medical School and Rehabilitation Institute of Chicago, IL, USA
› Institutsangaben
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Publikationsverlauf

Received 24. Oktober 1990

Accepted 03. April 1991

Publikationsdatum:
25. Juli 2018 (online)

Summary

The goal of this study was to determine the long-term clinical outcome of Human Immunodeficiency Virus (HIV) infection in a group of HIV-seropositive hemophiliacs for whom the dates of seroconversion were known and to investigate whether the use of monoclonal antibody purified factor (high purity) concentrate and treatment with zidovudine may alter the effect of HIV infection in seropositive hemophiliacs.

Twenty-eight hemophiliacs were followed for up to 9 years after seroconversion. In addition, 13 seropositive patients who elected to receive (high purity) factor VIII concentrate for up to 1.5 years were compared to a contemporaneous concurrent control group of 8 seropositive patients treated with intermediate purity factor VIII concentrate, and then both groups were followed for an additional 1.5 years while receiving zidovudine.

The acquired immunodeficiency syndrome (AIDS) developed in 9 of 28 patients (33%) from 1 to 9 years following seroconversion. CD4 cell count declined at a rate of 13.5% per year for the cohort but for persons 25 years and above the rate was significantly higher (17.5 ± 9.2% per year vs. 9.5 ± 4.7%, mean ± SD, p <0.05) than in those under 25. All three patients who had undergone splenectomy developed AIDS.

Subjects treated with high purity concentrates, with the exception of one patient who developed the nephrotic syndrome secondary to amyloidosis, had stable CD4 cell counts. On the other hand, all patients receiving intermediate purity concentrates had a decline in CD4 cells, and the difference from initial levels was highly significant (p = 0.01). The CD4 cell concentrations in these patients were stable after treatment with zidovudine.

We conclude that the incidence of AIDS in seropositive hemophiliacs more than 9 years after seroconversion is similar to that seen in other seropositive groups. CD4 cell counts declined more rapidly in those patients who were older at the time of seroconversion. Splenectomy may adversely affect the outcome of HIV infection.

Individuals receiving high purity concentrate may have less immunosuppression than those receiving intermediate purity concentrates. Randomized controlled trials are needed to confirm these observations.

 
  • References

  • 1 Smit C, Rosendaal FR, Varekamp I, Brocker-Vriends A, Van Dijk H, Suurmeijer TPBM, Birët E. Physical condition, longevity and social performance of Dutch haemophiliacs, 1972-1985. Br Med J 1989; 298: 235-8
  • 2 Sullivan JL, Brewster FE, Brettler DB, Forsberg AD, Cheeseman SH, Byron RS, Baker SM, Willitts DL, Lew RA, Levine PH. Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate. LAV/HTLV-III and herpes viruses. J Pediatr 1986; 108: 504-10
  • 3 Margolick JB, Volkman DJ, Folks TM. HTLV-III/LAV infection by antigen induced activation of T-cells and amplification of direct suppression by virus of lymphocyte blastogenic responses. J Immunol 1987; 138: 1719-23
  • 4 Eyster ME, Gail MH, Ballard JO, Ali-Mondiry H, Goedert JJ. Natural history of human immunodeficiency virus infection in hemophiliacs: effects of T-cell subsets, platelet counts and age. Ann Intern Med 1987; 107: 1-6
  • 5 Eyster ME, Ballard JO, Gali MH, Drummond JE, Goedert JJ. Predictive markers for the acquired immunodeficiency syndrome (AIDS) in hemophiliacs: persistence of p24 antigen and low T4 cell count. Ann Intern Med 1989; 110: 963-9
  • 6 Goldsmith JM, Kalish SB, Green D, Chmiel JS, Wallemark C-B, Phair JP. Sequential, clinical and immunologic abnormalities in hemophiliacs. Arch Int Med 1985; 145: 431-4
  • 7 Nishanian P, Taylor JM, Korns E, Detels R, Saah A, Fahey JL. Significance of quantitative enzyme-linked immunosorbent assay (ELISA) results in evaluation of three ELISAs and Western blot tests for detection of antibodies in a high risk population. J Clin Microbiol 1987; 25: 395-400
  • 8 Giorgi JV, Nishanian PG, Schmid I, Hultin LE, Cheng HL, Detels R. Selective alterations in immunoregulatory lymphocyte subsets in early HIV (human T-lymphotropic virus type III/lymphadenopathy associated virus infection). J Clin Immunol 1987; 7: 140-50
  • 9 Kalish SB, Goldsmith JM, Phair JP, Green D, Hsu CCS. Acquired immunodeficiency syndrome in a patient with multiple risk factors. Arch Int Med 1983; 143: 2310-1
  • 10 CDC Classification System for human T-lymphotropic virus type III/lymphadenopathy-associated virus infection. MMWR 1986; 35: 334
  • 11 Cozzi PJ, Abu-Jawdeh GM, Green RM, Green D. Amyloidosis in association with human immunodeficiency virus (HIV) infection. Rev Infect Dis, in press.
  • 12 Bernard DB. Extrarenal complications of the nephrotic syndrome. Kidney Int'l 1988; 33: 1184-202
  • 13 Evatt BL, Gomberts ED, McDougal JS, Ramsey RB. Coincidental appearance of LAV/HTLV-III antibodies in hemophiliacs and the onset of the AIDS epidemic. N Engl J Med 1985; 312: 483-6
  • 14 Eyster ME, Goedert JJ, Sarngadharan MG, Weiss SH, Gallo RC, Blattner WA. Development and early natural history of HTLV-III antibodies in persons with hemophilia. JAMA 1985; 253: 2219-23
  • 15 Lederman MM, Ratnoff OD, Evatt BL, McDougal JS. Acquisition of antibody to lymphadenopathy-associated virus in patients with classic hemophilia factor VII deficiency. Ann Intern Med 1985; 102: 753-7
  • 16 Andes WA, Daul DB, DeShazo RD, Palmer CH. Seroconversion of human immunodeficiency virus (HIV) in hemophiliacs: relation to lymphoadenopathy. Transfusion 1988; 28: 98-102
  • 17 Daul CB, DeShazo RD, Andes WA. Human immunodeficiency virus infection in hemophiliac patients: a three year prospective evaluation. Am J Med 1988; 84: 801-9
  • 18 Johnson RE, Lawrence DN, Evatt BL, Bregman DJ, Zyla LD, Curran JW, Aledort LM, Eyster ME, Brownstein AP, Carmen CJ. Acquired immunodeficiency syndrome among patients attending hemophilia treatment centers and mortality experience of hemophiliacs in the United States. Am J Epidemiol 1985; 121: 797-810
  • 19 Goldsmith JC, Dewhurst S, Hedenskog M, Casareale D, Volsky DJ. High prevalence and high titers of LAV/HTLV-III antibodies in healthy hemophiliacs in the Midwestern United States. Am J Med 1986; 81: 579-83
  • 20 Lambert T, Laurian Y, Verroust F, Mielot F, Larrieu MJ. Longitudinal study of LAV/HTLV-III infection in 260 French hemophiliacs. Second Intl Conf on AIDS, Paris: June 2-5 1986. p 102 (Abstract)
  • 21 Goedert JJ, Biggar RJ, Weiss SH, Eyster ME, Melbye M, Wilson S, Ginzburg HM, Grossman RJ, Digiolia RA, Sanchez WC, Grion JA, Ebbesen P, Gallo RC, Blattner WA. Three year incidence of AIDS in five cohorts of HTLV-III infected risk group members. Science 1986; 231: 992-7
  • 22 Andes WA, Wulff K, Mercer D, Ohene-Frempong K, Patin J. Coagulation factor concentrate usage and the risk of lymphadenopathy: a prospective study. Am J Med Sci 1986; 26: 142-6
  • 23 Beth-Giraldo E, Giraldo G, DeBiasi R, Miraglia E, Castello G, Perna M, Zarrilli D, Piazzi M, Cataldo PT, Ceparano S. Human immunodeficiency virus in hemophiliac patients: a 4 year prospective study. Antibot Chemother 1987; 38: 66-79
  • 24 Moss AR, Bacchetti P, Osmond D, Krampf W, Chaisson RE, Stites D, Wilber J, Allain JP, Carlson J. Seropositivity for HIV and the development of AIDS or AIDS related condition: three years follow up of the San Francisco General Hospital Cohort. Br Med J 1988; 296: 745-50
  • 25 Allain JP, Laurian Y, Paul DA, Verroust F, Leuther M, Gazengel C, Senn D, Larrieu MJ, Bosser C. Long-term evaluation of HIV antigen and antibodies to p24 and gp41 in patients with hemophilia: potential clinical importance. N Engl J Med 1987; 317: 1114-21
  • 26 Goedert JJ, Biggar RJ, Melbye M, Mann DL, Wilson S, Gail MH, Grossman RJ, DiGioia RA, Sanchez WC, Weiss SH, Blattner WA. Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus. JAMA 1987; 257: 331-4
  • 27 Polk BF, Fox R, Brookmeyer R, Kanchanaraksa S, Kaslow R, Visscher B, Rinaldo C, Phair JP. Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men. N Engl J Med 1987; 316: 61-6
  • 28 Lang W, Anderson RE, Perkins H, Grant RM, Lyman D, Winkelstein W, Royce R, Levy JA. Clinical, immunologic and serologic findings in men at risk for acquired immunodeficiency syndrome. JAMA 1987; 257: 326-30
  • 29 Barbui T, Cortelazzo S, Minetti B, Galli M, Buelli M. Does splenectomy enhance risk of AIDS in HIV-positive patients with chronic thrombocytopenia?. Lancet 1987; 2: 342-3
  • 30 Rocino A, Quirino AA, Miraglia E, Ziello L, Mastrullo L, DeBiasi R. Prospective controlled trial of an ultra-pure factor VIII concentrate to evaluate the effects on the immune status of HIV antibody-positive hemophilia patients (preliminary results). Acta Toxicol Ther 1990; 11: 49-58
  • 31 Brettler DB, Forsberg AD, Levine PH, Petillo J, Lamopn K, Sullivan JL. Factor VIII: C concentrate purified from plasma using monoclonal antibodies: human studies. Blood 1989; 3: 1859-63