- Association of Treatments for Anemia and Survival Among Persons With HIV Infection and Anemia (Poster 1154)
Authored by P. Sullivan, S. Buskin
Anemia in the setting of HIV disease is common, especially among women, African Americans and those with more advanced disease. It can be caused by a variety of mechanisms, including toxicities from medications used to treat HIV or its complications (e.g., zidovudine [AZT, Retrovir], dapsone, trimethoprim-sulfamethoxazole, ganciclovir, etc.).
Other mechanisms include HIV-induced inflammation (anemia of chronic disease), nutritional deficiencies (vitamin B12, folate or iron), blood loss, opportunistic infections and AIDS-related malignancies. Anemia symptoms (fatigue, rapid heartbeat, shortness of breath, headaches, etc.) can range from mild to severe, and anemia is associated with decreased survival in HIV-positive individuals. Additionally, anemic HIV-positive patients who recover from anemia have improved survival rates. Previously published reports from the pre-HAART era have demonstrated that HIV-positive anemic patients treated with recombinant human erythropoietin (epoetin-alfa, Procrit) had an associated decreased risk of death, while those treated with transfusions had an associated increased risk of death.
At present, there is only limited data available looking at the prevalence of anemia and the effect of various anemia treatments on survival among HIV-positive individuals receiving HAART. The present study was designed to characterize the prevalence of anemia and the outcomes associated with anemia and its treatments during the HAART era.
Methods and Results
HIV-positive individuals were followed through the Seattle Adult/Adolescent Spectrum of HIV-Related Diseases (ASD) Study. This Centers for Disease Control and Prevention (CDC)-sponsored project involved periodic medical record reviews of 2,408 HIV-positive patients between January 1996 and December 2001.
Anemia was defined as a hemoglobin less than or equal to 10.5 g/dL on the first visit. Patients were then followed every six months until death or loss to follow-up (defined as no contact for 18 months). Information collected included disease outcome, history of blood transfusions, and use of erythropoietin (epoetin-alfa, Procrit) therapy. Results were adjusted for baseline CD4 count, viral load, hemoglobin level and HAART use.
One thousand eight hundred and fifty-four patients (77 percent) had anemia diagnosed at some point over the six-year period of observation. The prevalence of anemia was greater in patients with a full AIDS diagnosis, and there was a decrease in the overall prevalence of anemia from 1996 to 2001. However, in those patients with a CD4 count of less than 100 cells (29 percent), the prevalence of anemia did not decline over the six-year study period.
Two hundred and sixteen anemic HIV-positive patients (mean hemoglobin 8.1 g/dL, mean CD4 count 140 cells/µl) were followed for a mean of 13 months. The overall mortality rate was 37 percent. Twenty-two percent received no treatment for their anemia, 42 percent received only blood transfusions, 12 percent received only erythropoietin (Procrit) and 24 percent received both blood transfusions and erythropoietin. Those patients treated with blood transfusions had an increased risk of death not seen in those treated with erythropoietin.
These results demonstrate that in the HAART era, just as in the pre-HAART era, there is an associated increased risk of mortality for HIV-positive anemic patients treated with blood transfusions.
This study was not designed to prove if this association was or was not a cause (blood transfusion) and affect (death) phenomenon. However, the study does reinforce current guidelines that consistently recommend anemia management with non-transfusion alternatives whenever possible. These therapies include optimization of antiretroviral regimens, provision of nutritional supplements when indicated (iron, vitamin B12, folate) and treatment with recombinant erythropoietin (epoetin-alfa, Procrit).
This study is of vital importance to both physicians and people living with HIV. These results were carefully adjusted to account for AIDS status, HAART use, CD4 cell count, viral load and hemoglobin level (severity of anemia). The highly significant three-fold increase in death among those receiving blood transfusions relative to those not receiving transfusions is impressive, and once again reminds us of the importance of monitoring and appropriately treating HIV-related anemia. The treatment of anemia in patients with HIV should be considered when hemoglobin levels fall below 12 g/dL in men and 11 g/dL in women, according to the current guidelines of the Anemia in HIV Working Group (Volberding, 2000).
It's interesting to note that the latest guidelines for the initiation of HAART in HIV-positive patients have shifted to favor treatment at a more advanced stage of disease (CD4 cell count less than 350 cells/µl). Certainly, the goal of this change is to avoid exhausting therapeutic options for later-stage disease; however, an unintended consequence of delaying HAART could be the reversal of the HAART-associated reduction in HIV-related anemia.
In light of the availability of a simple blood test to easily diagnose anemia, several therapeutic options to treat anemia, and additional data associating increased mortality with the use of blood transfusions as a treatment for anemia, vigilance for the early diagnosis and appropriate treatment of HIV-related anemia, on the part of both the treating physician and HIV-infected person, is warranted and could be life-saving.