[Treatment Horizons
by Chael Needle

Anemia, an abnormally low number of red blood cells, is one of the most common causes of fatigue in people with HIV—as many as seventy to eighty percent of HIV-positive individuals develop anemia at some time during the course of infection. When anemic, the body tries to compensate in a number of ways—the heart rate increases, putting an increased burden on the heart muscle; the respiratory rate increases; and blood is redistributed due to fluctuations in certain capillary beds.

Even in the era of HAART, it’s important to keep tabs on the problematic relationship between anemia and HIV. That’s what the Anemia and HIV Working Group seeks to address through publishing their retrospective reviews of medical literature and own expert opinions. First convened in 1998, the Working Group is a “nationwide group of experts brought together to look at the state of the art of the impact of anemia on the course of disease,” says Dr. Paul A. Volberding, a researcher at the University of California, San Francisco, who focuses most of his research lens on antiretroviral therapies but, like many others in the Group, has a strong interest in hematology and oncology as they relate to HIV. The Group’s most recent statement was published in the May 15 issue of Clinical Infectious Diseases, and included reminders of anemia’s contribution to fatigue and lower quality of life in those living with HIV/AIDS as well as the importance of epoetin alfa as a significant treatment for those without correctable causes of anemia.

One of the major differences between the earlier and current statements is the source data the Group looked at; in 1998, the Group extrapolated their findings from oncology data and didn’t have the wide breadth of research on the treatment of anemia in HIV patients that they have now, says Dr. Volberding. The Group found that the prevalence of severe anemia has decreased since the introduction of HAART, but mild-to-moderate anemia remains a problem for about half the patients receiving HAART. The Group suggests, however, that physicians and patients pay attention to these less severe forms of anemia. “It’s clear that if you can keep patients healthier overall, there will be less severe anemia,” says Dr. Volberding. Better health, in this case, might be a matter of better nutrition, he notes, citing the fact that many with advanced AIDS endure a lot of wasting illness.

The Group reported that, in the HAART era, anemia is significantly more common among women and African-Americans who are HIV-positive; other risk factors include zidovudine use, increasing age, and lower body-mass index, among others. Dr. Volberding says that a complex set of conditions leads to anemia, but medicine has a fairly firm grasp on how to evaluate it. Nutritional issues such as vitamin B-12 and folic acid deficiencies can be anticipated and prevented. “Drug-related anemia also can be anticipated and prevented from a careful selection of medications,” he continues. “Then you have the effect of HIV itself, which can be reduced by effective antiretroviral therapies. While there are a lot of things that good medical care and overall attention to health can do to prevent the development of severe anemia, a certain degree of anemia is probably not preventable by our current approaches.” He adds: “That might be due to the chronic inflammation of HIV infection itself.” 

Most striking when one looks at the studies that have been conducted, says Dr. Volberding, “is that anemia emerges as an independent predictor of disease progression and mortality in HIV infection. Even independent of CD4 cell count and viral load, anemia contributes to accelerated disease progression and death. The question we are very interested in—and trying to explore—is whether the reversal of anemia will also be associated with slower disease progression and death in the way HIV treatment itself has achieved.”

A clinical trial could be designed to prove whether or not the reversal of anemia can improve survival, he says, “but the survival [rate] now in [those living with] HIV is so good that it would take huge numbers of patients to prove.” He suggests that a retrospective, rather than prospective, study might be more insightful. “But at the same, we hope that basic investigators would try to understand that if this is true—that there’s a cause and effect—what the linkage might be.”

Chael Needle wrote about the microbicide candidate, Carraguard, in the August issue.

September 2004