Dissident AIDS Database

Co-factorsHemophilia / factor VIIIAIDS symptomsImmuno-deficiency
Immunological abnormalities in haemophilia: are they caused by American factor VIII concentrate?
 Froebel, K.S., R. Madhok, C. Forbes, S.E. Lennie, G.D. Lowe & R.D. Sturrock
  Froebel et al. also argued against the hypothesis that immunodeficiency in American hemophiliacs was due to a virus, and suggested that it was due to treatments with factor VIII because "Scottish patients with hemophilia, most of whom had received no American factor VIII concentrate for over two years, were found to have immunological abnormalities similar to those in their American counterparts ..."
  Br. Med. J. 287: 1091-1093, 19831983
Association of HTLV-III antibodies and cellular immune status of hemophiliacs.
 Tsoukas, C., F. Gervais, J. Shuster, E. Gold, M. O'Shaughnessy & M. Robert-Guroff
  Tsoukas et al observed that amongst a group of 33 asymptomatic haemophiliacs receiving factor VIII concentrates, 66% were immunodeficient "but only half were seropositive for HTLV-III", while "anti-HTLV-III antibodies were also found in the asymptomatic subjects with normal immune function". They summarised their findings as follows: "These data suggest that another factor (or factors) instead of, or in addition to, exposure to HTLV-III is required for the development of immune dysfunction in haemophiliacs"
  N. Engl. J. Med. 31: 1514-1515, 19841984
Impaired immune function in hemophilia patients treated exclusively with cryoprecipitate: relation to duration of treatment.
 Pollack, S., D. Arias, G. Yoffe, R. Katz, Y. Shechter & I. Tatarsky
  "Derangement of immune function in hemophiliacs results from transfusion of foreign proteins or a ubiquitious virus rather than contracting AIDS infectious agent". In 1985 HIV was extremely rare in blood concentrates outside the U.S., but immunodeficiency was observed in Israeli, Scottish, and American hemophiliacs.
  Am. J. Hematol. 20: 1-6, 19851985
Immunologic and virologic status of multitransfused patients: Role of type and origin of blood products.
 AIDS-Hemophilia French Study Group
  "... Allogenic or altered proteins present in factor VIII ... seem to play a role of immunocompromising agents... A correlation between treatment intensity and immunologic disturbances was found in patients infused with factor VIII preparations, irrespective of their positive or negative LAV [HIV] antibody status"
  Blood, 1985, 66: 896-9011985
Immunological alterations in anti-HTLV-III negative haemophiliacs and homosexual men in Hungary.
 Hollan, S.R., G. Fuest, K. Nagy, A. Horvath, G. Krall, K. Verebelyi, E. Ujhelyi, L. Varga & V. Mayer,
  Likewise, Hollan et al. reported in 1985 "an immunodeficiency independent of HTLV-III infection" in Hungarian hemophiliacs.
  Immunol, 1985, Letters 11: 305-3101985
Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.
 Madhok, R., A. Gracie, G.D.O. Lowe, A. Burnett, K. Froebel, E. Follett & C.D. Forbes
  "Clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV"
  Br. Med, 1986, J. 293: 978-980.1986
HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia.
 Jason, J.M., J.S. McDougal, G. Dixon, D.N. Lawrence, M.S. Kennedy, M. Hilganner, L. Aledort & B.L. Evatt
  Jason et al. from the CDC observed that, "Hemophiliacs with immune abnormalities may not necessarily be infected with HTLV-III/LAV, since factor concentrate itself may be immune suppressive even when produced from a population of donors not at risk for AIDS".
  J. Am. Med. Assoc, 1986 255: 212-215.1986
Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses.
 Sullivan, J.L., E.E. Brewster, D.B. Brettler, A.D. Forsberg, S.H. Cheeseman, K.S. Byron, S.M. Baker, D.L. Willitts, R.A. Lew & E.H. Levine,
  Sullivan et al. deduced from a comprehensive study of hemophiliacs that "hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate [etc.] ... Seropositivity to LAV/HTLV-III (HIV) was 70% for the hemophiliac population and ... varied directly with the amount of factor VIII received".
  J. Pediatr, 1986, 108: 504-5101986
Factor concentrates for treatment of hemophilia: which one to choose?
 Brettler, D.B. & P.H. Levine
  "Factor concentrate itself, perhaps secondary to the large amount of foreign-protein present, may cause alterations in the immune systems of hemophiliac patients"
  Blood 73: 2067-2073, 19891989
T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates.
 Menitove, J.E., R.H. Aster, J.T. Casper, S.J. Lauer, J.L. Gottschall, J.E. Williams, J.C. Gill, D.V. Wheeler. V. Piaskowski, P. Kirchnet & R.R. Montgomery
  Menitove et al. described a correlation between immunosuppression of hemophiliacs and the amount of factor VIII received over a lifetime; the more factor a hemophiliac had received the lower was his T4/T8-cell ratio. Their data were found to be "consistent with the possibility that commercially prepared lyophilized factor VIII concentrates can induce an AIDS-like picture ..."
  N. Engl. J. Med. 308: 83-86, 19831983
Abnormalities of circulating lymphocyte subsets in haemophiliacs in an AIDS-free population.
 Carr, R., E. Edmond, R.J. Prescott. S.E. Veitch, J.E Peutherer & C.M. Steel
  Carr et al. studied immunodeficiency in HIV-positive and HIV-negative hemophiliacs and proposed "that the abnormalities [low T4 to T8 cell ratios] result from transfusion of foreign proteins"
  Lancet, 1984, i: 1431-14341984
Human T-Lymphotropic Virus Type-III (HTLV-III) Infection in Seronegative Hemophiliacs after Transfusion of Factor VIII.
 Ludlam CA et al.
  "Between April and October, 1984, anti-HTLV-III [HIV antibodies] developed in 16 patients with hemophilia A...[of whom] all but one had received a common batch [of clotting] factor VIII...a further eighteen patients received the implicated batch A...[but] have been negative for [HIV antibodies]...The 15 patients who seroconverted used significantly more vials of batch A and also had a higher annual factor VIII consumption than the eighteen patients who did not seroconvert...Our finding in this study that T-helper-cell numbers and the helper/suppressor ratio did not change after infection supports our previous conclusion that the abnormal T-lymphocyte subsets [CD4/CD8 cells] are a result of the intravenous infusion of factor VII concentrates per se, not [HIV] infection”
  Lancet. 1985 Aug 3;2(8449):233-236.1985
Immunoresponsiveness in hemophilia: lymphocyte- and phagocyte-mediated functions.
 Antonaci S, Jirillo E, Stasi D, De Mitrio V, La Via MF, Bonomo L
  Antonaci et al found decreased CD4/CD8 ratios as well is impaired CD4 function in HIV-negative hemophiliacs, stating in their conclusion that "Our findings clearly indicate an impairment of immune function in hemophiliacs regardless of HIV infection".
  Diagn Clin Immunol;5(6):318-25, 19881988
Effect on Lymphocyte Subsets of Clotting Factor Therapy in Human Immunodeficiency Virus-I-Negative Congenital Clotting Disorders.
 Hassett, J., G.E. Gjerset. J.W. Mosley, M.A. Fletcher. E. Donegan, J.W. Parker, R.B. Counts. L.M. Aledort, H. Lee, M.C. Pike & Transfusion Safety Study Group,
  Hassett et al. reported that "patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1 ) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls". The study observed an average T4/T8-cell ratio of 1.47 in a group of 307 HIV-free hemophiliacs, differing over 50 years in age, compared to an average of 1.85 in normal controls. Unlike others, Hassett et al. attributed the lowered CD4+ counts to a hemophilia-related disorder rather than to foreign proteins, but like others they attributed increased CD8+ counts to treatment with commercial factor VIII.
  Blood 82: 1351-1357. 1993.1993
Blood products and immune changes: impacts without HIV infection.
 Aledort, L.M.,
  “It has been suggested that chronically transfused hemophiliacs have T-cell abnormalities that have occurred independently of their HIV status...when we took a look at the HIV-negative [hemophiliac] patients who were recipients of Factor VIII [clotting] concentrates, we found that the T4/T8 ratios were significantly reduced compared to the control group and significantly reduced compared to those who were recipients of single-donor plasma...Recipients of Factor VIII, Factor IX...demonstrated significant T-cell abnormalities regardless of the presence of the HIV antibody”
  Sem. Hematol, 1988, 25: 14-191988
Human immunodeficiency virus-I disease progression in hemophiliacs.
 Becherer, ER., M.L. Smiley, T.J. Matthews, K.J. Weinhold, C.W., McMillan & G.C.I. White
  Becherer et al. showed that immunodeficiency in hemophiliacs increases with both the age and the cumulative dose of clotting factor received during a lifetime.
  Am. J. Hematol, 1990, 34: 204-2091990
Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort.
 Simmonds, P., D. Beatson, R.J.G. Cuthbert, H. Watson, B. Reynolds, J.F. Peutherer, J.V. Parry, C.A. Ludlam & C.M. Steel,
  Even among HIV-positive hemophiliacs "The rate of disease progression, as assessed by the appearance or not of AIDS symptoms or signs within five years of seroconversion, was related ... to the concentration of total plasma IgM before exposure to infection ..."
  Lancet, 1991, 338: 1159-1163.1991
The significance of T lymphocytes in transfusion medicine.
 Prince, H.
  "When serum samples from these [immunodeficient hemophilia] patients were tested for antibodies to HIV-1, it was found that a sizable group of hemophilia patients, usually 25% to 40%, were seronegative for HIV-1," and "... all found marked anergy, lack of response, in HIV-seronegative concentrate recipients. Taken together, these findings were interpreted as evidence that clotting factor concentrates suppressed the immunocompetence of recipients ...".
  Transfus. Med. Rev, 1992, 16: 32-431992
Factor concentrate is a co-factor.
 Maynard, T
  The editor of aids News, published by the Hemophilia Council of California, granted foreign proteins the role of a cofactor of HIV in hemophilia AIDS with an editorial "Factor concentrate is a Co-factor"
  Aids News, 1994, (Hemophilia Council of California) 8: 1.1994
The acquired immunodeficiency syndrome in patients with hemophilia.
 Evatt, B.L., R.B. Ramsey, D.N. Lawrence, L.D. Zyla & J.W. Curran
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (in the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years). According to Evatt, "This age bias may be due to differences in duration of exposure to blood products ..."
  Ann. Intern. Med. 100: 499-505. 1984.1984
AIDS and Hemophilia.
 Koerper, M.A.
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (in the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years). According to the hematologist Koerper, "this may reflect lifetime exposure to a greater number of units of concentrate, ..."
  AIDS: Pathogenesis and Treatment, pp. 79-95, J.A. Levy (ed.) Marcel Dekker, Inc., New York, 19891989
Incidence of AIDS and excess mortality associated with HIV in haemophiliacs in the United Kingdom: report on behalf of the directors of haemophilia centers in the United Kingdom.
 Darby, S.C., C.R. Rizza, R. Doll, R.J.D. Spooner, I.M. Stratton & B. Thakrar,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (in the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years).
  Br. Med. J. 298: 1064-1068, 1989.1989
AIDS incubation in 1891 HIV seroconverters from different exposure groups.
 Biggar, RJ. & the International Registry of Seroconverters,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (In the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years). The annual AIDS risk of HIV-positive hemophiliacs also shows a strong age bias : the annual AIDS risk of children was estimated at 1% and that of adult hemophiliacs at 3% over a 5-year period of HIV-infection.
  AIDS 4: 1059-1066. 1990.1990
HIV epidemiology: past, present, and future.
 Blattner, W. A.
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (in the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years).
  FASEB J. 5: 2340-2348. 19911991
A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia.
 Goedert, J.J., C.M. Kessler, L.M. Aledort, R.J. Biggar, W.A. Andes, G.C. Whim II, J.E. Drummond, K. Vaidya, D.L. Mann, M.E. Eyster, M.V. Ragni, M.M. Lederman, A.R. Cohen, G.L. Bray, ES. Rosenberg, R.M. Friedman, M.W. Hilgartner, W.A. Blattner, B. Kroner & M.H. Gail.
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => the annual AIDS risk of HIV-positive hemophiliacs shows a strong age bias : in the U.S., Goedert et al. reported that the annual AIDS risk of 1- to 17-year-old hemophiliacs was 1.5%, that of 18- and 34-year-old hemophiliacs was 3%, and that of 64- year-old hemophiliacs was 5%
  N. Engl. J. Med. 321: 1141-1148. 1989.1989
CD4 Cells in HIV-1 Infected Hemophiliacs: Effect of Factor VIII Concentrates.
 Goldsmith, J .M., J. Deutsche, M. Tang & D. Green,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => the annual AIDS risk of HIV-positive hemophiliacs shows a strong age bias : Goldsmith et al. reported that the annual T-cell loss of hemophiliacs under 25 years was 9.5% and for hemophiliacs over 25 years 17.5%
  Thromb. Haemost. 66: 415-419. 1991.1991
Progression of HIV disease in a haemophiliac cohort followed for 11 years and the effect of treatment.
 Lee, C.A., A.N. Phillips, J. Elford, G. Janossy, P. Griffiths and E. Keruoff,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => the annual AIDS risk of HIV-positive hemophiliacs shows a strong age bias : Lee et al. reported that the annual AIDS risk of hemophiliacs 11 years after HIV seroconversion was 31% under 25 years and 56% over 25 years. They estimated that the relative risk of AIDS increased 5-fold over 25 years.
  Br. Med. J. 303: 1093-1096. 1991.1991
Use of CD4 lymphocyte count to predict long term survival free of AIDS after HIV infection.
 Phillips, A.N., C.A. Sabin, J. Elford, M. Bofill, G. Janossy & C.A. Lee
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => the annual AIDS risk of HIV-positive hemophiliacs shows a strong age bias : this group confirmed in 1994 that the annual AIDS risk of HIV-positive hemophiliacs over 30 years is 2-times higher than in those under 15 years of age
  Br. Med. J. 309: 309-313. 19941994
Geographic variability of hemophilia-associated AIDS in the United States: effect of population characteristics.
 Stehr-Green, J.K., J.M. Jason, B.L. Evatt & the HemophiliaAssociated AIDS Study Group,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => Statistics show that the median age of hemophiliacs with AIDS in the U.S. and other countries is about 5-15 years higher than the average age of hemophiliacs (in the U.S., the average age of hemophiliacs was 20-27 years from 1980 to 1986, while that of hemophiliacs with AIDS was 32-35 years). The annual AIDS risk of HIV-positive hemophiliacs also shows a strong age bias : Stehr-Green et al. estimated that "... the risk of AIDS increased two fold for each 10 year increase in age after controlling for year of seroconversion" and that "repeated exposure to factor concentrate ... could also account for more rapid progression of HIV infection with age."
  Am. J. Hematol. 32: 178-183, 1989.1989
Effect of Age on Human Immunodeficiency Virus Type I-Induced Changes in Lymphocyte Populations Among Persons with Congenital Clotting Disorders.
 Fletcher, M.A., J.W. Mosley, J. Hassea, G.E Gjerset, J. Kaplan, J.W. Parker, E. Donegan, J.M. Lusher, H. Lee & Transfusion Safety Study Group,
  According to the foreign-protein hypothesis, immunodeficiency in hemophilia patients is proportional to the lifetime dose of foreign proteins received and thus, the annual AIDS risk of a hemophiliac increases with age => the annual AIDS risk of HIV-positive hemophiliacs shows a strong age bias : Fletcher et al. reported a 4-fold higher incidence of AIDS in hiv+ hemophiliacs over 25 years of age than in those aged 5 to 13 years. This study also showed that even in HIV-free hemophiliacs, "with increasing age, numbers of CD4+CD45RA+ cells decreased and continued to do so throughout life". Fletcher et al. also described a positive "relationship between the amount of concentrate administered and anti-HIV prevalence rate ..."
  Blood 80: 831-840. 1992.1992
FOREIGN-PROTEIN-MEDIATED IMMUNODEFICIENCY IN HEMOPHILIACS WITH AND WITHOUT HIV
 Duesberg Peter
  According to the foreign-protein hypothesis, hiv seropositivity in hemophilia patients is a marker to 1) the number of transfusions received before hiv (a rare contaminant of factor VIII) was eliminated from the blood supply in 1984, 2) the lifetime dose of foreign proteins received and 3) the foreign-protein mediated immuno-deficiency. => "Twenty-one studies, summarized in Table 3, have observed 1,186 immunodeficient hemophiliacs, 416 of whom were HIV-free. Immunodeficiency in these studies was either defined by a T4 to T8-cell ratio of about 1 or less than 1, compared to a normal ratio of 2, or by other tests such as immunological anergy. Since immunodeficiency was observed in the absence of HIV, most of the studies listed in Table 3 have concluded that immunodeficiency in hemophiliacs was caused by transfusion of factor VIII and contaminating proteins. Nevertheless, several of the controlled studies listed in Table 3, which compare HIV-negative to HIV-positive hemophiliacs, have shown that immunodeficiency is more often associated with HIV-positives than with negatives... Some of the investigators listed in Table 3, and others who have not performed controlled studies, have proposed that HIV is just a marker for the number of transfusions received."
  Genetica 95: 51-70, 19951995
Factor VIII products and disordered immune regulation.
 Gordon, R.S.
  "Repeated administration of factor VIII concentrate from many varied donors induces a mild disorder of immune disregulation by purely immunological means, without the intervention of infection."
  Lancet i: 991, 19831983