Transmission in Hemophiliacs

““From ‘87 [the year that AZT was approved], all we [hemophiliacs and their families] saw was people dying,” said Alice, her hair white at 51. “And believe me, when you see someone dying of AIDS, it’s really bad. It’s different each time. No one dies the same way.””

“An HIV-positive man who didn’t tell his girlfriend he had the condition was sentenced to 12 years in prison Thursday…Neither [his girlfriend nor another sexual partner] contracted HIV despite their long-term relationship with Hunter, Jones said…Court documents said Hunter has hemophilia and got HIV through a blood transfusion when he was 7 years old. He attended the University of Arkansas, where he met at least one of the women.”

“HIV-1 testing became available in 1984…During 1977–1984, mortality in individuals with severe haemophilia remained constant at 0.9%. Among HIV-uninfected individuals, mortality remained at this level during 1985–1999. In contrast, among HIV-infected individuals, mortality increased progressively to 2.5, 4.3, 5.8, 8.1, and 12.7% in the years 1985–1986, 1987–1988 [when AZT was approved for use outside clinical trials], 1989–1990, 1991– 1992, and 1993–1994, respectively. In 1995– 1996 annual mortality was 11.3%, before falling to 5.3% in 1997–1999, after the introduction of HAART. For individuals with moderate/mild haemophilia, annual mortality during 1977–1984 was 0.4%. This is half the corresponding value in individuals with severe haemophilia, and the difference is principally caused by the lower mortality from causes involving bleeding. For individuals with moderate/mild haemophilia without HIV, annual mortality remained at 0.4% throughout 1985–1999. For individuals with moderate/mild haemophilia with HIV, annual mortality increased progressively, to 2.5, 2.6, 5.9, 8.1, 11.5, and 13.1% in years 1985–1986, 1987–1988, 1989–1990, 1991– 1992, 1993–1994, and 1995–1996, before falling to 2.9% in 1997–1999…when mortality from other [non-HIV] causes was examined separately, a substantial increase over time remained, with the value during 1991–1996 almost double that for 1985–1990 and no appreciable decline in 1997–1999. The increase was entirely caused by an increase in liver disease, which during 1997–1999 was the certified cause of death for over 25% of deaths in HIV-infected individuals…For deaths that were classified neither as HIV related nor from liver disease, mortality remained virtually constant during 1985–1999, albeit at a higher level than that of HIV-uninfected individuals. It seems likely that at least some of these deaths were attributable to HIV, although there was no indication that the individuals concerned had developed an AIDS-defining condition. HAART has been associated with several categories of major toxic effects, but there was no evidence of any deaths occurring as a result of HAART in this population. [but what other explanation is there?]”

“Surprisingly sera/plasmas obtained from high-risk HIV-1 seropositive hemophiliacs prior to seroconversion more often contained alloreactive antibodies than date-matched sera/plasmas obtained from HRSN [high-risk, HIV-negative] hemophiliacs. Thus alloreactivity may predispose to acquisition of HIV-1 infection after parenteral exposure [ignoring the possibility that it is exposure to larger quantities of clotting factor that both generates the alloreactive antibodies and ‘HIV’ antibodies as well as being a risk factor for AIDS]”

“A significant number of those [hemophiliacs] receiving batches [of Factor VIII clotting compound] known to be infected [with HIV] did not seroconvert [become HIV-positive]”

“The chronology of studies investigating immunodeficiency in HIV-free hemophiliacs faithfully reflects the popularity of the HIV hypothesis: the more popular the HIV hypothesis became over time the fewer studies investigated immunodeficiency in HIV-free hemophiliacs. Indeed, most of the controlled studies investigating the role of HIV in immunodeficiency of HIV-positive and matched HIV-negative hemophiliacs were conducted before the virus hypothesis became totally dominant in 1988, namely between 1984 and 1988 . The studies by Jin, Cleveland and Kaufman, and Lang et al., both dated 1989, and the studies by Becherer et al. and by Jason et al., both dated 1990, all described data collected before 1988. After 1988 the question whether HIV-free hemophiliacs developed immunodeficiency became increasingly unpopular. As a result, only a few studies have described immunodeficiency in HIV-free hemophiliacs.”

“In this review, the association between the Acquired Immune Deficiency Syndrome (AIDS) and haemophilia has been carefully examined, especially the data that have been interpreted as indicating transmission of the human immunodeficiency virus (HIV) to the recipients of purportedly contaminated factor VIII preparations. In our view, the published data do not prove the hypothesis that such transmission occurs, and therefore HIV cannot account for AIDS in haemophiliacs.”

“We interviewed 31 of the 47 patients [hemophiliacs] identified with [HIV-negative AIDS, involving low immune cell counts (lymphocytopenia) and no record of positive HIV tests] and 23 of their contacts…19 persons had AIDS-defining illnesses (18 had opportunistic infections), 25 had conditions that were not AIDS-defining [except for their low CD4 cell counts] and 3 were asymptomatic…The investigation of contacts revealed no evidence of a new transmissible agent that causes lymphocytopenia.”

“Early in 1988, 13 patients were elected to receive monocolonal antibody purified factor VII (high purity [blood clotting] concentrate)…[if one patient with a severe drop of CD4 counts due to another disease is omitted from analysis] the CD4 value for the remaining 12 patients in the high purity group is 308 +/- 158, not significantly different from the baseline value. On the other hand, the CD4 value for the subjects treated with intermediate purity concentrate fell significantly (to 176 +/- 148). While 5 subjects in the high purity group had an increase in CD4 counts, all patients receiving intermediate purity concentrate had a decrease in the CD4 cell count.”

“HIV was recovered from only 2 of 16 spouses of the seropositive hemophiliacs whom we studied…This inefficient heterosexual transmission of HIV in hemophiliacs seems different than that observed in other groups where one partner is bisexual or an intravenous drug addict [ignoring the possibility of higher levels of health risk in partners within these other groups]”

“Infection with HIV was studied in 14 sexually active spouses of infected hemophilic men who had been HIV antibody reactive for a mean of 46 months. One half of the hemophilic men studied had overt HIV antigenemia for a mean duration of 27 months; 6 of the men studied fulfilled clinical criteria for the diagnosis of AIDS. All 14 couples were sexually active in a strictly monogamous fashion, in marriages of [an average duration of] 13.5 years with an average reported frequency of 4 sexual encounters per month…Antibodies to HIV developed in only one of the 14 wives. At the time when this seroconversion was detected, her husband, in whom AIDS developed, had been reactive for HIV antibody for 49 months, and showed positive findings for HIV antigen for 26 months. No additional risk factors were identified for this couple. The infected female spouse, however, has a 14-year history of multiple sclerosis, and had been treated with immunosuppressant intermittently. Despite a significantly reduced number of CD4 lymphocytes, she has remained clinically asymptomatic for 17 months since seroconversion. HIV antibodies did not develop in any of the 13 remaining wives, despite the frequent practice of oral sex by six couples and reports of occasional anal intercourse by another couple.”

“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”

“HTLV-III [HIV]-seropositive hemophiliac subjects, on average, had been exposed to twice as much concentrate during the previous year as seronegative hemophiliac subjects. The seropositive group had a significantly lower mean helper/suppressor T cell ratio and absolute helper T cell level that the seronegative group...It is concluded that HTLV-III antibody occurs with high frequency in hemophiliac subjects, and is related to the amount of factor VIII or IX concentrate infused.”

“Only two (2.3%) of 88 individuals without hemophilia [who were sexual partners and/or lived with hemophiliacs] had antibody to HTLV-III/LAV [HIV]”

“We report the apparent spread of LAV [HIV] in a white American family from husband to wife through heterosexual contact. Although the wife remained clinically well, she developed LAV antibody and a decreased number of T-helper cells. She was followed for 10 months; after exposure to her husband’s semen was discontinued, the LAV antibody was no longer detectable and the T-helper cell number returned to normal [all other family members were consistently negative and clinically well] [This example violates the belief that HIV infections cannot be overcome by the body without drugs, and that HIV antibodies are unambiguous proof of HIV infection]”

“No one has reported the isolation of HTLV-III/LAV [HIV] from antihemophilic factor using macroculture isolation techniques despite compelling evidence that this material transmits AIDS”

“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”

“we studied a group of 65 adult hemophiliacs for T-cell subset abnormalities [e.g. low CD4 cell counts]. 65% of concentrate recipients had an abnormal T-helper to T-suppressor cell ratio, 40% had a depressed absolute T-helper cell level, and 29% had an elevated absolute T-suppressor cell count…we [also] studied 41 [of their] spouses. We found no correlation between paired husband and wife values for T-cell ratio or any other immune parameter studied. There were no significant differences found between wives of hemophiliacs with reversed T-cell ratios and wives of hemophiliacs with T-cell ratios of 1.0 or greater, with respect to immunologic tests. We conclude that there is no evidence to date for heterosexual or household-contact transmission of T-cell subset abnormalities from hemophiliacs to their spouses in our study population.”

“in most cases, low levels of exposure to [clotting] factor VIII were associated with normal OKT4/OKT8 [CD4/CD8] ratios…The hemophiliac patients with persistent lymphadenopathy in our study received more factor concentrate therapy and had more profound perturbations of T-lymphocyte numbers and function”