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

Abstract

SummaryThe 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.

Foreign-protein-mediated immunodeficiency in hemophiliacs with and without HIV

“…Moreover, four out of six anergic HIV-positive patients treated with purified factor VIII recovered immunological activity (de Biasi et al, 1991). Goldsmith et al also found that the T-cell counts of 13 hemophiliacs treated with purified factor VIII remained stable for 1.5 years (Goldsmith et al, 1991). Seremetis et al have confirmed and extended de Biasi et al's conclusion by establishing that the Tcells of HIV-positive hemophiliacs were not depleted after treatment with pure factor VIII for three years (Seremetis et al, 1993).…”

“…AZT has been recommended and prescribed to symptomatic HIV carriers since 1987 Richman et al, 1987) and to healthy HIV carriers with lower than 500 T-cells since 1988 (Volberding et al, 1990;Goldsmith et al, 1991;Phillips et al, 1994b). Approximately 200,000 HIV antibodypositives with and without AIDS diseases are currently prescribed AZT worldwide (Duesberg, 1992a).…”

“…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 hemohiliacs was 3%, and that of 64-year-old hemophiliacs was 5% (Goedert et al, 1989). 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% (Goldsmith et al, 1991). 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 (Lee et al, 1991).…”

“…However, despite the evidence that purified factor VIII is beneficial in maintaining or even increasing Tcell counts, several studies testing purified factor VIII are ambiguous about its effectiveness in preventing or treating AIDS (Goldsmith et al, 1991;Hilgartner et al, 1993;Gjerset et al, 1994;Goedert et al, 1994;Phillips et al, 1994a). Some of these studies have only tested partially purified, i.e.…”

No effect of a new second‐generation B‐domain‐deleted recombinant product on lymphocyte transformation in vitro: a study of plasma‐derived and recombinant products

“…This issue might be important not only for the development of inhibitors, but also for replacement therapy in haemophiliacs with associated immune defects such as HIV. In this context, it is noteworthy that monoclonal antibody (Mab)-purified CFCs may stabilize the CD4 þ cell count in HIV-infected haemophiliacs, although it has not been possible to correlate this effect to improved clinical outcome (de Biasi et al, 1991;Goldsmith et al, 1991;Mannucci et al, 1992;Seremetis et al, 1993;Hilgartner et al, 1993).…”