The prevalence of anemia in HIV-positive people has been well described in several studies. Anemia remains the most common hematological complication of HIV disease, occurring in nearly 30% of asymptomatic patients and in 75% to 80% in patients with clinical AIDS.1 It can result in dramatic consequences for anyone living with HIV disease. Anemia in HIV disease has been associated with an increased progression to clinical AIDS, decreased survival, fatigue, decreased quality of life, the need for erythropoietin therapy, and blood transfusion.2-3

In general, women experience anemia more often than men due to monthly menstrual blood loss. However, there have been few studies that have examined this clinical manifestation in HIV-positive females. Two recent studies have been conducted that address this problem.

Semba and colleagues performed a longitudinal study that examined anemia in HIV-positive females (n = 797) and compared them to an HIV-negative (n = 389) cohort. Over 60% of the HIV-positive women developed anemia over the 5.4 years of study. Anemia occurred at the highest rate among women who had a CD4 lymphocyte count of less than 200 cells/uL. The rate was lowest among women whose CD4 count was greater than 500 cells/uL.4

The Human Immunodeficiency Virus Epidemiology Study (HERS) not only examined the prevalence but also assessed for risk factors associated with anemia. In addition to the lower CD4 count, other risk factors were found to be increasing age (in 5 year increments), African American race, zidovudine use, and morbidities such as fever for greater than 2 weeks, weight loss, diarrhea, oral candidiasis, Mycobacterium avium complex, bacterial pneumonia, and Pneumocystis carinii pnemonia.4

In a similar study Levine and colleagues examined anemia in 2,056 HIV-positive females and 569 HIV-negative females enrolled in the Women's Interagency HIV Study (WIHS). Since the etiology of anemia in HIV infection is diverse, the researchers examined what clinical correlates existed in HIV-positive women.5

Generally, the causes of anemia can include abnormalities of red blood cell production, increased red blood cell destruction, or ineffective production (ie, vitamin B12 deficiency). In addition, anemia in HIV disease is frequently associated with decreased serum erythropoietin levels, various opportunistic infections, and some anti-HIV medications (ie, zidovudine).1,4,5

The findings of the Levine study support the need for vigilant anemia assessment. Factors that correlated to the development of anemia in the HIV-positive female included an inverse relationship between hemoglobin levels and viral loads greater than 50,000 copies. As was previously detailed, the CD4 count was also predictive of anemia, as was the development of clinical AIDS.

African American females are thought to be biologically burdened by anemia because of the higher prevalence of a and b thalassemia traits in this cohort. Also of note, anemia was found more frequently in women with low mean corpuscular volume (MCV) in their red blood cells.5

Several studies have defined anemia as a hemoglobin level of less than 12 g/dl.4,5 Some researchers have postulated that, given the profound clinical implications of anemia in HIV disease, other parameters should be employed.6

Based on the high incidence of anemia in HIV-infected patients, appropriate screening, diagnosis, management, and treatment is essential and may prolong survival and increase quality of life. Screening for anemia should begin with the first visit and should be repeated at the same time that CD4 count and viral loads are assessed (every 2 to 3 months). Evaluation should include a complete history and physical examination, documentation of signs and symptoms, and laboratory tests (hemoglobin/ hematocrit levels, iron levels, folic acid). A hemoglobin? level <1g/dL below the normal reference level can be diagnosed as anemia; factors such as age, gender and pregnancy should also be considered, because normal hemoglobin levels vary according to patient characteristics.6 Therefore, to minimize these differences, it is recommend that a diagnosis of mild, moderate, and severe anemia be based on a graded decrease in hemoglobin concentration from that considered to be normal for the individual patient. Further evaluation of anemia should include quality of life (QOL) questionnaires (eg, Medical Outcomes Study HIV Health Survey, The Functional Assessment of Human Immunodeficiency Virus) that can be used to assess fatigue, functional status, and activities of daily living in an anemic patient. Symptomatic patients at a hemoglobin level suggestive of mild anemia may be considered to be more severely anemic than those who have the same hemoglobin level but who are asymptomatic.6

Once the patient is properly diagnosed and evaluated, treatment should be initiated. Treatment goals include maintaining a normal hemoglobin concentration, improving overall QOL, and alleviating signs and symptoms. The treatment of anemia in any patient, including those with HIV infection, should whenever possible correct the underlying cause of anemia (eg, opportunistic infection, nutritional deficiency, myelosuppressive drugs) because this by itself may correct the problem. Patients are treated according to severity (mild, moderate, and severe) with either red blood cell transfusion or human recombinant erythropoietin (epoetin alfa). Transfusion, indicated for severe anemia, provides immediate increase in hemoglobin concentration and improvement in energy levels, but is associated with an increased risk of death, transfusion reaction, and immunosuppression.7 Epoetin alfa, on the other hand, has been associated with increased survival, as well as improvements in anemia and QOL, and is indicated for the treatment of moderate anemia. Consideration should be given to instituting iron supplementation to ensure the best response to epoetin alfa. Asymptomatic patients diagnosed with mild anemia should receive nutritional support, should participate in aerobic exercise, and should be monitored at least every 2 months.

For these treatment regimens to be appropriately administered, education and support is crucial. If blood transfusion is required to correct anemia, it is essential to provide safe patient care and administration of the blood product, and to educate patients and caregivers about the importance of reporting adverse events (fever, chills, pruritus, rash, shortness of breath). For patients receiving epoetin alfa, careful instructions on the proper drawing up of the product and on storage and disposal should be provided. Patients need to be counseled on the benefits of proper nutrition, the use of vitamin supplements, exercise, and adequate rest. Moreover, patients should be educated to report fatigue, shortness of breath, rapid heart rate, and light-headedness as obvious signs of anemia and not to consider these as unimportant or untreatable complications associated with HIV infection.

In summary, increased awareness about the prevalence and implications of anemia in patients infected with HIV implies increased vigilance in screening and diagnosis in this patient population. This is especially important for females. Patients should be queried about symptoms associated with anemia, and hemoglobin levels should be checked at every evaluation in which viral load and CD4 lymphocyte counts are routinely made. Obvious causes of anemia should be treated. Safe, effective treatment in the form of epoetin alfa is available for anemia of chronic disease.?

See Dr. Ferri's bio on page 85.

?References

???? 1.?? Levine AM. Anemia, neutropenia, and thrombocytopenia: pathogenesis and evolving treatment options in HIV infected patients. In: HIV Clinical Management, Vol 10. Available at: , Accessed May 4, 2002.

???? 2.?? Moore RD. Human immunodeficiency virus infection, anemia, and survival. Clin Infectious Dis. 1999;29:44-49.

???? 3.?? Barroso J. A review of fatigue in people with HIV infection. J Assoc Nurses in AIDS Care. 1999;10:42-49.

???? 4.?? Semba RD, Shah N, Klein RS, et al. Prevalence and cumulative incidence of and risk factors for anemia in a multicenter cohort study of the human immunodeficiency virus: infected and uninfected women. Clin Infectious Dis. 2002;34:.

???? 5.?? Levine AM, Berhane K, Masri-Lavine L, et al. Prevalence and correlated of anemia in a large cohort study of HIV-infected women: women's interagency study. HIV Treatment Bulletin. 2001;26:28-35.

???? 6.?? Ferri RS, Adinolfi A, Orsi A, et al. Treatment of anemia in patients with HIV infection, Part 2. J Assoc Nurses in AIDS Care. 2002;13:50-59.

???? 7.?? Hillyer CD, Lankford KV, Roback JD, Gillespie TW, Silberstein LE. Transfusion of the HIV-seropositive patient: immunomodulation, viral reactivation, and limiting exposure to EBV (HHV-4), CMV (HHV-5), and HHV-6, -7, and -8. Transfusion Med Rev. 1999;13:1-17.