Antimitotic agents

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Kaposi's sarcoma

The vinca alkaloids vinblastine and vincristine are both effective agents against Kaposi's sarcoma. Vinblastine is more toxic to the bone marrow than vincristine, especially when used in combination with doxorubicin. Bleomycin, also effective in Kaposi's sarcoma, does not usually lead to marrow suppression, whereas etoposide, another very effective agent, can lead to severe neutropenia. The suppressive effects of antimitotic agents are more pronounced in advanced HIV disease when the marrow is already compromised by the effects of HIV and, possibly, by concurrently administered antimicrobial or antiretroviral agents.

AIDS-related lymphoma

The problems of chemotherapy in NHL associated with HIV infection have been discussed earlier. As in Kaposi's sarcoma, the more powerful combinations of chemotherapeutic agents are significantly immunosuppressive and run the risk of precipitating opportunistic infections at the same time as provoking serious bone marrow suppression.

Hepatitis C in HIV disease

Hepatitis C virus (HCV) is especially common among haemophiliacs and intravenous drugs users, most of whom carry both viruses. As deaths from HIV disease are declining as a result of HAART, liver disease has become an increasing cause of morbidity and mortality. The immunodeficiency associated with HIV infection accelerates the course of HCV infection and the hepa-totoxicity of anti-HIV drugs poses particular problems.

HIV antibody-positive patients who fulfil standard criteria for chronic hepatitis C (persistent elevated aminotransaminase levels, detectable serum HCV-RNA and necroinflammatory activity with portal or bridging fibrosis in the liver biopsy) respond less well to combination treatment with interferon-a and ribavirin than HIV antibody-negative patients, although this is linked to the degree of immunosuppression. Slow-release interferon-a, covalently bound to polyethylene glycol (pegylated form) can provide continuous exposure to interferon-a with a single weekly injection. Ribavirin can cause haemolytic anaemia, although this is not usually severe. Care should be taken when it is prescribed along with other nucleoside analogues (especially zidovudine) that cause bone marrow suppression and ddI, which causes severe mitochondrial toxicity.

Selected bibliography

Bain BJ (1997) The haematological features of HIV infection. British Journal of Haematology 99: 1-8.

Bain BJ (1998) Lymphomas and reactive lymphoid lesions in HIV infection. Blood Reviews 12: 154-62.

Bower M (2002) The management of lymphoma in the im-munosuppressed patient. Best Practice and Research in Clinical Haematology 15: 517-32.

Caldena V, Chermann JC (1992) The effects of HIV on hema-topoiesis. European Journal of Haematology 48: 181-6.

Centres for Disease Control and Prevention (CDC) (1992) Revised classification system for HIV infection and expanded surveillance care definition for AIDS among adolescents and adults. Centres for Disease Control and Prevention (CDC), Atlanta, GA, 1992. Morbidity and Mortality Weekly Report 41: 1-19.

Cohen AJ, Philips TM, Kessler CM (1986) Circulating coagulation inhibitors in the acquired immunodeficiency syndrome. Annals of Internal Medicine 104: 175-80.

Coyte TE (1997) Haematological complications ofhuman immunodeficiency virus infection and the acquired immunodeficiency syndrome. Medical Clinics of North America 81: 449 -70.

Doweiko JP (1993) Management of the hematologic manifestations of HIV disease. Blood Reviews 7: 121-6.

Harriman GR, Smith PD, Horne MK etal. (1989) Vitamin B12 malabsorption in patients with acquired immunodeficiency syndrome. Archives of Internal Medicine 149: 2039-41.

Henry DH, Beall GN, Benson CA et al. (1992) Recombinant human erythropoietin in the treatment of anaemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials. Annals of Internal Medicine 117: 739-48.

Henry K, Costello C (1994) HIV-associated bone marrow changes. Current Diagnostic Pathology 1: 131-41.

Holland HK, Spivak JL (1990) The haematological manifestations of acquired immune deficiency syndrome. Baillières Clinical Haematology 3: 103-14.

Kaczmarski RS, Mufti GJ (1993) The pathophysiology and management of HIV-associated haematological abnormalities. Haemato-logia 25: 1-17.

Karcher DS, Frost AR (1991) The bone marrow in human immunodeficiency virus (HlV)-related disease. American Journal of Clinical Pathology 95: 63-71.

Karpatkin S (1990) HIV-related thrombocytopenia. Bailliere's Clinical Haematology 3: 115-38.

Levine AM (2000) Acquired immunodeficiency syndrome-related lymphoma: clinical aspects. Seminars in Oncology 27: 442-53.

Levine AM (2001) Anaemia in HIV Infection. Journal of the International Association ofPhysicians in AIDS Care Winter (Suppl.): 61-72.

Little RF, Pittaluga S, Grant N etal. (2003) Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumour biology. Blood 101: 4653-9.

Miles SA (1992) Hematopoietic growth factors as adjuncts to antiretroviral therapy. AIDS Research on Human Retroviruses 8: 1073-80.

Moses A, Nelson J, Bagby GC Jr (1998) The influence of human immunodeficiency virus-I on hematopoiesis. Blood 91: 1479-95.

Panel of Clinical Practices for Treatment of HIV Infection (1999) Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents, 5 May 1999, online. Available: http://www.hivatis.org (16 December 1999).

Rodriguez-Rosado R, Garcia-Samaniego J, Soriano V (1999) Hepatitis C, an emerging problem in HIV-infected patients. AIDS Review 1: 22-8.

Scaradovou A (2002) HIV-related thrombocytopenia. Blood Reviews 16: 73-6.

Wickramasinghe SN, Beatty C, Sheils S et al. (1992) Ultrastructure of the bone marrow in HIV infection: evidence of dyshaemo-poiesis and stromal cell damage. Clinical and Laboratory Haematology 14: 213-29.

The major histocompatibility complex and human leucocyte antigens, 395 Structure of HLA proteins, 396 Antigen processing and presentation, 396 HLA function, 397 HLA nomenclature, 397 HLA polymorphism, 399

HLA associations with disease, 399 HLA matching in transplantation, 413 Histocompatibility testing procedures, 414

Serology, 414 DNA methods, 414

Sequence-specific oligonucleotide and sequence-specific primer methods, 414

Direct sequencing, 415 Ambiguities, 416 Conformational methods, 416 Cellular assays, 417 Other genetic polymorphisms, 418 Selected bibliography, 418

The major histocompatibility complex and human leucocyte antigens, 395 Structure of HLA proteins, 396 Antigen processing and presentation, 396 HLA function, 397 HLA nomenclature, 397 HLA polymorphism, 399

HLA associations with disease, 399 HLA matching in transplantation, 413 Histocompatibility testing procedures, 414

Serology, 414 DNA methods, 414

Sequence-specific oligonucleotide and sequence-specific primer methods, 414

Direct sequencing, 415 Ambiguities, 416 Conformational methods, 416 Cellular assays, 417 Other genetic polymorphisms, 418 Selected bibliography, 418

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