Epidemiology of Anemia in Human Immunodeficiency Virus (HIV)-Infected Persons: Results From the Multistate Adult and Adolescent Spectrum of HIV Disease Surveillance Project

I. Introduction

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To study the incidence of, the factors associated with, and the effect on survival of anemia in human immunodeficiency virus (HIV)-infected persons, we analyzed data from the longitudinal medical record reviews of 32,867 HIV-infected persons who received medical care from January 1990 through August 1996 in clinics, hospitals, and private medical practices in nine United States cities. We calculated the 1-year incidence of anemia (a hemoglobin level of <10 g/dL or a physician diagnosis of anemia); the adjusted odds ratios showing excess risk of anemia associated with demographic fectors, prescribed therapies, and concurrent diseases; the risk of death for patients who developed anemia compared with risk for patients who did not develop anemia; and, of patients who did develop anemia, the risk of death for those who did not recover from anemia compared with the risk for those who did recover. The 1-year incidence of anemia was 36.9% for persons with one or more acquired immunodeficiency syndrome (AIDS)-defining opportunistic illnesses (clinical AIDS), 12.1% for patients with a CD4 count of less than 200 cells/µm or CD4 percentage of <14 but not clinical AIDS (immunologic AIDS), and 3.2% for persons without clinical or immunologic AIDS. Of anemia diagnoses, 22% were identified by physicians as drug related. Incidence of anemia was associated with clinical AIDS, immunologic AIDS, neutropenia, thrombocytopenia, bacterial septicemia, black race, female sex, prescription of zidovudine, fluconazole, and ganciclovir, and lack of prescription of trimethoprim-sulfamethoxazole. The increased risk of death associated with anemia differed by first CD4 count: for patients with a CD4 count of > or = 200 cells/µL at the beginning of the survival analysis, the risk of death was 148% (99% confidence interval [CI], 114 to 188) greater for those who developed anemia; for patients whose first CD4 count was <200 cells/µL, the risk of death was 56% (99% CI, 43 to 71) greater for those in whom anemia developed. For persons in whom anemia developed, the risk of death was 170% (99% CI, 132 to 203) greater for persons who did not recover from anemia compared with those who did recover. Anemia is a frequent complication of HIV infection, and its incidence is associated with progression of HIV disease, prescription of certain chemotherapeutics, black race and female sex. Anemia, particularly anemia that does not resolve, is associated with shorter survival of HIV-infected patients.

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Anemia is a frequent complication of infection with the human immunodeticiency virus type 1 (HIV-1) and may have multiple causes.⁽¹⁾ In different study settings, the prevalence of anemia in persons with acquired immunodeficiency syndrome (AIDS) has been estimated at 63% to 95%,^(2-5) making it more common than thrombocytopenia or leukopenia in patients with AIDS.^{(3, 6)} This high prevalence of anemia may be because of a high incidence of anemia, a long duration of anemia, or a combination of both.

HIV infection may lead to anemia in many ways: changes in cytokine production with subsequent effects on hematopoiesis;^(7-9) decreased erythropoietin concentrations;^{(10, 11)} opportunistic infectious agents, such as Mycobacterium avium complex⁽¹²⁾ and parvovirus B-19;⁽¹³⁾ administration of chemotherapeutic agents such as zidovudine,⁽¹⁴⁾ ganciclovir,⁽¹⁵⁾ and trimethoprim-sulfamethoxazole;⁽¹⁶⁾ and myelophthisis caused by cancers such as lymphosarcoma. Other mechanisms for HIV-associated anemia, although uncommon, include vitamin B₁₂ deficiency⁽¹⁷⁾ and the autoimmune destruction of red blood cells.⁽¹⁸⁾ Direct infection of marrow precursor cells⁽¹⁹⁾ has been hypothesized, but not proven.

Anemia has been associated with progression to AIDS⁽²⁰⁾ and shorter survival times^{(21, 22)} for HIV-infected patients. No published data have shown whether, given that anemia has developed, recovery from anemia is associated with improved survival. Understanding the association between anemia and survival is important because treatments for anemia are available including recombinant human erythropoietin (r-huEP0),⁽²³⁾ blood transfusion, and, in drug-induced anemia, cessation of myelosuppressive therapies.

To study the occurrence, associations, and effect of anemia on the survival of HIV-infected patients, we analyzed data from the medical records of 32,867 persons enrolled in a project that provided surveillance for opportunistic illnesses, other clinical conditions, drugs prescribed, and laboratory data for persons infected with HIV.

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