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Heterosexual Co-transmission of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)

OBJECTIVES To determine the prevalence of antibodies to hepatitis C virus (HCV) in female sexual partners of multitransfused men with hemophilia and to compare the frequency of transmission of HCV and human immunodeficiency virus (HIV). STUDY DESIGN Cross-sectional measurement of HCV and HIV antibodies. SETTING Ten hemophilia treatment centers. PATIENTS A total of 234 female sexual partners of 231 multitransfused men with hemophilia. MEASUREMENTS AND MAIN RESULTS The prevalence of antibodies to HCV (anti-HCV) among female sexual partners of HCV-positive men was 5 of 194 (2.6%). Anti-HIV prevalence among female sexual partners of HIV-positive men was 25 of 196 (12.8%). Five (3%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HCV compared with none of the 30 female sexual partners of HIV-negative/HCV-positive men. Twenty-one (13%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HIV compared with 4 (13%) of 32 female sexual partners of HIV-positive/HCV-indeterminate men. The co-infected men were five times more likely to transmit both viruses than would be expected by chance (P = 0.01). When a single virus was transmitted to a female sexual partner, it was more often HIV than HCV (18 of 164 compared with 2 of 164, P = 0.001; odds ratio, 8.5; 95% Cl, 2.2 to 33.1). CONCLUSIONS The higher prevalence of HCV in female sexual partners of men with hemophilia than in blood donor and other low-risk groups suggests that there is a low level of sexual transmission. Male to female sexual transmission of HCV is less efficient than that of HIV. The frequency of HCV transmission to sexual partners is five times higher when HIV is also transmitted, suggesting that HIV may be a cofactor for the sexual transmission of HCV.

Efficacy and safety of vapor‐heated anti‐inhibitor coagulant complex in hemophilia patients. FEIBA Study Group

The study reported here was designed to measure the efficacy and safety of a vapor‐heated anti‐inhibitor coagulant complex (FEIBA‐VH) for the treatment of bleeding episodes in patients with hemophilia A who have inhibitors to factor VIII (FVIII). FEIBA‐VH, a second‐generation complex, is vapor‐heated for 10 hours at a temperature of 60°C and a pressure of 1190 millibar (mbar) and for 1 additional hour at 80°C and 1375 mbar. The current study was performed because of concern that this vapor‐heating process would reduce the efficacy of FEIBA‐VH as compared with non‐heat‐treated FEIBA (FEIBA). Forty‐one patients received FEIBA‐VH for 106 evaluable bleeding episodes. Ninety‐ three (88%) episodes were controlled, and 13 (12%) were not. Eighty‐ three (79%) episodes were controlled within 36 hours of the first infusion. No significant toxicity was seen. These results were compared with those of an earlier study with FEIBA. FEIBA‐VH was at least as effective as FEIBA in controlling bleeding episodes and can be compared favorably to any reported treatment of bleeding episodes in hemophiliacs with inhibitors to FVIII.

Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status

The availability of monoclonal-antibody-purified factor VIII (FVIII) concentrates allows us to test the hypothesis, based on in vitro observations, that their use in HIV seropositive haemophiliacs would result in a difference in the rate of deterioration of immune function. We designed a multicentre, prospective, randomised, controlled study of symptom-free HIV-infected patients with haemophilia A who were assigned to receive either an intermediate-purity or monoclonal-antibody-purified product. All had CD4 lymphocyte counts of 100-600/microL, were negative for hepatitis B surface antigen, had not received any antiretroviral or immunomodulating drugs before study entry, and had previously received replacement therapy with intermediate purity FVIII concentrates. Use of antiretroviral therapy was permitted. 60 patients were recruited and 30 were assigned to each group. 35 completed the 3 year study, 20 in the monoclonal arm and 15 in the intermediate-purity arm. Among those completing the study, there were no differences between the two groups in the occurrence of AIDS-defining diagnoses (1 in each group). There were, however, striking and significant differences in terms of changes in absolute CD4 counts. The group receiving monoclonal-antibody-purified concentrates had essentially stable counts while a significant drop was observed in the group receiving intermediate-purity FVIII. These differences were independent of the use of antiretroviral therapy. These observations support the use of high-purity concentrates in the treatment of symptom-free HIV-positive patients with haemophilia A, and they should be taken into account along with cost, by doctors making therapeutic decisions.

Low risk of viral infection after administration of vapor-heated factor VIII concentrate

A multicenter prospective study was carried out to evaluate whether a vapor‐heated factor VIII concentrate transmitted blood‐borne viral infections over a surveillance period of 15 months. Thirty‐five patients with hemophilia and von Willebrand disease who had never received any blood components were treated. Twenty‐eight were analyzed and found not to have non‐A,non‐B hepatitis. Sera from 20 of these 28 patients were also tested for the antibody to the hepatitis C virus. None had sero‐converted during the follow‐up period. None of the patients analyzed developed markers of the hepatitis B virus (n = 17) or the human immunodeficiency virus (n = 31). This vapor‐heated factor VIII concentrate carries a low risk of transmitting hepatitis and human immunodeficiency virus infection.

Comparison of the recovery and half‐life of a high‐purity factor IX concentrate with those of a factor IX complex concentrate. Factor IX Study Group

BACKGROUND: Recovery and half‐life estimations were carried out to compare a high‐purity factor IX concentrate with an established factor IX complex concentrate. STUDY DESIGN AND METHODS: Two high‐purity factor IX concentrates, which are identical except for the presence or absence of heparin (Immuninehep‐plus and Immuninehep‐minus), were evaluated in two independent crossover studies using an intermediate‐ purity factor IX complex concentrate (Bebulin) as reference drug. RESULTS: In the Immuninehep‐plus crossover study (n = 27), Immuninehep‐ plus and Bebulin had, respectively, a recovery of 0.90 +/− 0.26 and 0.84 +/− 0.23 IU per dL per IU per kg, a compartmental half‐life of 17.11 +/− 6.18 and 15.94 +/− 4.69 hours, and an effective half‐life of 16.51 +/− 3.48 and 16.48 +/− 4.26 hours. In the Immuninehep‐minus crossover study (n = 26), Immuninehep‐minus and Bebulin had, respectively, a recovery of 0.92 +/− 0.31 and 1.02 +/− 0.36 IU per dL per IU per kg, a compartmental half‐life of 17.42 +/− 5.60 and 18.77 +/− 6.27 hours, and an effective half‐life of 16.39 +/− 4.44 and 16.48 +/− 4.28 hours. Equivalence tests indicated that the recovery and half‐life of Immunine, with or without heparin, are equivalent to those of Bebulin. CONCLUSION: The equivalence in pharmacokinetics and bioavailability indicates that the dosage schedule for Immunine should be the same as or very similar to that of Bebulin. The high specific activity of the former, however, allows administration at lower volumes.

Low risk of viral infection after administration of vapor-heated factor VII concentrate or factor IX complex in first-time recipients of blood components. International Factor Safety Study Group

BACKGROUND: Vapor‐heated human factor VII concentrate and human factor IX complex are both obtained from prothrombin complex, undergo similar methods of manufacture, and are subjected to an identical two‐step vapor‐heating process for virus inactivation. STUDY DESIGN AND METHODS: Intermediate‐purity vapor‐heated human factor VII concentrate and vapor‐ heated human factor IX complex were monitored for safety with regard to viral infection in the context of an International Factor Safety Study, a prospective study that follows the revised recommendations from the International Congress of Thrombosis and Hemostasis (ICTH). Because the rarity of the respective hereditary deficiencies would have made separate analyses unrealizable, the results were combined for the final analysis. Entry required that patients have no history of transfusion with any blood derivative. After the first infusion of the study drug, patients were monitored for 6 months for the development of non‐A, non‐ B hepatitis (NANBH) and infection with hepatitis B virus (HBV) and for 15 months for infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). An event was defined as a positive result on any test for any infection. An alanine aminotransferase level more than 2.5 times the upper limit of normal on two consecutive occasions was defined as an event for NANBH. HBV infection was monitored with tests for three different HBV markers: the HBV surface antigen, antibody against the HBV surface antigen, and antibody against HBV core antigen. HCV and HIV infection were monitored with tests for HCV and HIV antibodies. RESULTS: The 25 patients who completed the study (1 has not completed the study and 1 dropped out) received a total of 434 infusions comprising 17 different production lots of the concentrates. Twenty patients were analyzable for NANBH and 25 for HCV and HIV infection. Since most patients had been given HBV vaccination, only 4 patients were analyzable for this end point. None of the patients showed evidence of having developed an event. These data satisfy ICTH criteria when the products are considered together, but vapor‐heated factor VII concentrate does not qualify alone because there were only five patients in this group. CONCLUSION: Vapor‐heated factor VII concentrate and vapor‐heated factor IX complex are associated with a low risk of viral infection. Preliminary results are also presented, indicating that the concentrates are safe with regard to inhibitor development.