trimethoprim--sulfamethoxazole-drug-combination and Hemophilia-A

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes; Child; Desensitization, Immunologic; Drug Hypersensitivity; Female; Follow-Up Studies; Hemophilia A; HIV Infections; Humans; Leukocyte Count; Male; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

An 82-year-old man was referred to our hospital because of bilateral leg swelling and ecchymosis. A hemostatic study showed prolonged aPTT, <1% factor VIII coagulant activity, and a high titer (30.4 Bethesda Units/ml) of factor VIII inhibitor. The diagnosis of acquired hemophilia A (AHA) was made, and treatment with prednisolone (PSL) was started. Within one month of treatment, the hemorrhagic symptom disappeared, aPTT levels returned to normal, and his factor VIII inhibitor was eradicated; however, factor VIII inhibitor was detected again when PSL was decreased to 10 mg/day. We then added cyclosporine A (CyA) to PSL as a second line salvage therapy. CyA therapy resulted in the resolution of AHA with marked and prolonged efficacy; however, hot, red tumors appeared in his right arm and left thigh. Needle aspiration of the tumors revealed muscle abscess, and Nocardia brasiliensis was isolated. We started treatment with sulfamethoxazole-trimethoprim, and the abscess healed promptly without recurrence.

Topics: Abscess; Aged, 80 and over; Biopsy, Fine-Needle; Cyclosporine; Hemophilia A; Humans; Immunocompromised Host; Male; Muscular Diseases; Nocardia Infections; Opportunistic Infections; Prednisolone; Salvage Therapy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Allogenic proteins that contaminate intermediate purity clotting factor concentrates may activate the immune system of HIV-infected haemophilic patients. In 37 haemophilic patients infected with HIV who had originally been treated with intermediate purity factor VIII concentrate and then changed to monoclonally-purified high purity factor VIII concentrate the rates of CD4+ decline (10(9)/l per year) were 0.06 before and 0.02 after a switch to high purity products (p = 0.01). The median follow-up of patients after the switch to high purity products was 1.7 years (range 0.2 to 3 years). This significant change in the rate of CD4 decline was independent of the starting CD4 count, age and antiretroviral therapy. This result is consistent with those from randomised trials of the introduction of high-purity concentrate. Given the strong association between the CD4+ count and survival, treatment with high purity rather than intermediate purity clotting factor concentrate may confer a survival benefit for HIV-infected haemophilic patients.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Child; Child, Preschool; Cohort Studies; Disease Progression; Factor VIII; Fluconazole; Hemophilia A; HIV Infections; Humans; Male; Middle Aged; Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Drug Combinations; Drug Hypersensitivity; Hemophilia A; Humans; Male; Pneumonia, Pneumocystis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Adverse reactions to trimethoprim-sulfamethoxazole are very prevalent in patients with acquired immunodeficiency syndrome (AIDS). Recently we have observed severe toxicities associated with trimethoprim-sulfamethoxazole in three hemophiliacs, a group known to be at risk for developing AIDS. At the time of these reactions to the antibiotic, none of the patients had yet manifested any stigmata of AIDS per se. We advise caution in the use of trimethoprim-sulfamethoxazole in hemophiliacs and other patients at high risk for the development of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Drug Combinations; Hemophilia A; Humans; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In order to reveal the activity of polymorphonuclear neutrophil leukocytes (PMNL) representing the first step of defence against infections, measurements of chemiluminescence (CL) were performed in patients suffering from acquired immune deficiency syndrome (AIDS), lymphadenopathy, or hemophilia. In comparison with healthy controls, AIDS patients revealed significant reduction (about 50 per cent) of phagocytic, i.e. CL activity of neutrophils, which had been induced by Zymosan. Only part of the patients suffering from lymphadenopathy answered with decreased granulocyte activity on the application of Zymosan. If concanavalin A was used as stimulant of metabolic activity of PMNL-independently of phagocytosis-again AIDS and some of the lymphadenopathy patients showed a markedly reduced neutrophil response. In conclusion it should be stated that there is some evidence for at least two defects of cellular immunity associated with AIDS and to some extent, with AIDS-endangered homosexuals suffering from lymphadenopathy: first the defect of PMNL to answer to concanavalin A with increased metabolic activity, and secondly the defect of PMNL to start phagocytosis induced by Zymosan with a subsequent release of oxygen radicals which are measurable as chemiluminescence. The appraisal of granulocyte activity by means of measurements of chemiluminescence might become an additional criterion for AIDS diagnostics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Infective Agents, Urinary; Concanavalin A; Drug Combinations; Hemophilia A; Humans; Immunoglobulins; Luminescent Measurements; Luminol; Lymphoproliferative Disorders; Male; Neutrophils; Phagocytosis; Sulfamethoxazole; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Zymosan