Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Conventional clotting factor concentrates have, until recently, been “of intermediate purity,” containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

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Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Blood ◽

10.1182/blood.v73.7.1859.1859 ◽

1989 ◽

Vol 73 (7) ◽

pp. 1859-1863 ◽

Cited By ~ 28

Author(s):

DB Brettler ◽

AD Forsberg ◽

PH Levine ◽

J Petillo ◽

K Lamon ◽

...

Keyword(s):

Factor Viii ◽

Plasma Proteins ◽

Coagulation Factor ◽

Clotting Factor ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Clotting Factor Concentrates ◽

Cd4 Cell ◽

Hiv Seropositive

Abstract Conventional clotting factor concentrates have, until recently, been “of intermediate purity,” containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.

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Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group

Blood ◽

10.1182/blood.v83.7.1958.bloodjournal8371958 ◽

1994 ◽

Vol 83 (7) ◽

pp. 1958-1962

Author(s):

PM Mannucci ◽

DB Brettler ◽

LM Aledort ◽

JM Lusher ◽

CF Abildgaard ◽

...

Keyword(s):

Factor Viii ◽

Recombinant Factor Viii ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Factor Viii Concentrates ◽

Beta 2 ◽

Beta 2 Microglobulin ◽

Cd4 Cell ◽

Hiv Seropositive

Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2- microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

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Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group

Blood ◽

10.1182/blood.v83.7.1958.1958 ◽

1994 ◽

Vol 83 (7) ◽

pp. 1958-1962 ◽

Cited By ~ 19

Author(s):

PM Mannucci ◽

DB Brettler ◽

LM Aledort ◽

JM Lusher ◽

CF Abildgaard ◽

...

Keyword(s):

Factor Viii ◽

Recombinant Factor Viii ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Factor Viii Concentrates ◽

Beta 2 ◽

Beta 2 Microglobulin ◽

Cd4 Cell ◽

Hiv Seropositive

Abstract Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2- microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

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Deficient Antibody-Dependent Cellular Cytotoxicity against Human Immunodeficiency Virus (HIV)-Expressing Target Cells in Perinatal HIV Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.5.718-724.1999 ◽

1999 ◽

Vol 6 (5) ◽

pp. 718-724 ◽

Cited By ~ 10

Author(s):

Ulrike Ziegner ◽

Donald Campbell ◽

Kent Weinhold ◽

Ian Frank ◽

Richard Rutstein ◽

...

Keyword(s):

Nk Cell ◽

Target Cells ◽

Cellular Cytotoxicity ◽

Antibody Dependent Cellular Cytotoxicity ◽

Cd4 Cells ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Cd4 Cell ◽

Hiv Seropositive

ABSTRACT Peripheral blood mononuclear cells (PBMC) of human immunodeficiency virus (HIV)-infected children, age-matched HIV-seronegative controls, and HIV-infected asymptomatic and symptomatic adults were compared for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell-mediated cytotoxicity against target cells expressing HIV or herpes simplex virus (HSV) antigens. Target cells consisted of CD4 lymphocytes purified from PBMC of HIV-seronegative adults and incubated with the IIIB strain of HIV, HUT78 cells chronically infected with IIIB, and HSV-infected human fibroblasts. PBMC of asymptomatic HIV-infected adults were generally able to lyse CD4 cells expressing HIV antigens. Direct correlation was found between the magnitude of lysis and absolute CD4 cell counts in these individuals. In contrast to these results, PBMC from HIV-infected children were generally unable to lyse IIIB-expressing CD4 cells, regardless of the children’s clinical status, age, or absolute CD4 cell counts. Cells from HIV-seronegative adults and children did not directly lyse these target cells either but, in contrast to cells of HIV-seropositive children, were able to mediate cell lysis when serum from an HIV-seropositive adult was added. However, effector cells from these HIV-infected children were able to mediate both ADCC against HSV-infected fibroblasts and NK cell-mediated cytotoxicity against IIIB-infected HUT78 cells. Reduced ability of PBMC from vertically HIV-infected children to mediate ADCC against HIV antigen-expressing CD4 cells may contribute to rapid progression to AIDS.

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Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.11.2664 ◽

1996 ◽

Vol 40 (11) ◽

pp. 2664-2668 ◽

Cited By ~ 2

Author(s):

A M Been-Tiktak ◽

I Williams ◽

H M Vrehen ◽

J Richens ◽

D Aldam ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Transcriptase Inhibitor ◽

Viral Loads ◽

Nonnucleoside Reverse Transcriptase Inhibitor ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Reverse Transcriptase Inhibitor ◽

Cd4 Cell ◽

Hiv 1

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

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Primary Prophylaxis for Cryptococcosis With Fluconazole in Human Immunodeficiency Virus (HIV)-Infected Patients With CD4 Cell Counts <100 Cells/mm3 and Receiving Antiretroviral Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw194.61 ◽

2016 ◽

Vol 3 (suppl_1) ◽

Author(s):

Chutchaiwat Savetamornkul ◽

Warisara Pattanapongpaiboon ◽

Somnuek Sungkanuparph

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Primary Prophylaxis ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Cd4 Cell

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Acyclovir Use and Survival Among Human Immunodeficiency Virus‐Infected Patients with CD4 Cell Counts of < 500/mm

Clinical Infectious Diseases ◽

10.1086/516272 ◽

1998 ◽

Vol 26 (1) ◽

pp. 85-90 ◽

Cited By ~ 2

Author(s):

Ramón A. Torres ◽

James D. Neaton ◽

Deborah N. Wentworth ◽

Michael R. Barr ◽

Donald Abrams ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Immunodeficiency Virus ◽

Cd4 Cell

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TT Virus Is Present in a High Frequency of Italian Hemophilic Patients Transfused With Plasma-Derived Clotting Factor Concentrates

Blood ◽

10.1182/blood.v94.12.4333.424k11_4333_4336 ◽

1999 ◽

Vol 94 (12) ◽

pp. 4333-4336 ◽

Cited By ~ 1

Author(s):

Benjamin P. Chen ◽

Maria Grazia Rumi ◽

Massimo Colombo ◽

Yu-Huei Lin ◽

Latha Ramaswamy ◽

...

Keyword(s):

Factor Viii ◽

Odds Ratio ◽

Causal Effect ◽

Clotting Factor ◽

Hepatitis Viruses ◽

Tt Virus ◽

Plasma Factor ◽

Immunodeficiency Virus ◽

Factor Viii Concentrates ◽

Clotting Factor Concentrates

The prevalence of the blood-borne TT virus (TTV) in Italian hemophiliacs treated with different preparations of factor VIII was determined. Of the 178 hemophilic patients (mean age, 29 years), TTV-DNA was found in 123 (69%), in comparison to 22 of 100 (22%) blood donors (P < .0001). Of the 123 patients who tested positive for TTV, significant numbers were also infected with human hepatitis viruses and/or human immunodeficiency virus (HIV): 31% had TTV and hepatitis C virus (HCV), 22% had TTV, and at least 2 of the 4 known human blood-borne viruses tested, whereas 15% had TTV alone. The risk of acquiring TTV alone was only slightly higher in recipients of unmodified plasma factor concentrates (78%, odds ratio, 1.24; 95% confidence interval [CI], 0.27 to 5.79) than in patients treated with virus inactivated concentrates (67%), whereas the risk was significantly lower in recipients of recombinant factors (11%, odds ratio, 0.09; 95% CI, 0.01 to 0.52). Serum alanine aminotransferase (ALT) levels were elevated in 2 of 27 patients (7%) with TTV alone compared with 43 of 56 patients (77%) coinfected with TTV and HCV and compared with 16 of 21 patients (76%) with HCV alone. Taken together, these results indicate that TTV frequently infects Italian hemophiliacs treated with plasma-derived factor VIII concentrates, both unmodified and virus-inactivated. Our results do not suggest a causal effect of TTV on chronic liver disease in these patients.

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