While researchers have established that certain biological factors—such as coinfection with viral hepatitis, body-mass index and pretreatment CD4 count—can increase the likelihood of certain HIV treatment side effects, very little is known about the impact of race and gender on antiretroviral toxicity rates.

Beginning in 1993, the federally funded Community Programs for the Clinical Research on AIDS (CPCRA) enrolled 1,397 into a trial designed to compare three different antiretroviral regimen strategies as first-line therapy. Being compared in the Flexible Initial Retrovirus Suppressive Therapy (FIRST) study was a regimen that included a protease inhibitor (PI), a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a regimen involving both a PI and an NNRTI. The original analysis of the study found that all three regimens performed equally well in terms of suppressing and keeping virus at undetectable levels.

To determine what impact race and gender may have played on the incidence of side effects in the study, Ellen Tedaldi, MD, of the Temple Comprehensive HIV Program in Philadelphia and her CPCRA colleagues analyzed data involving 1,301 of the study participants. Of those, 20 percent were women, 17 percent were Hispanic and 54 percent were black. Overall the various groups were similar. Women, however, were more likely to start treatment with a higher CD4 count and lower viral load than men, and black participants were more likely to have started treatment with a lower CD4 count and to have high blood pressure at study entry.

During the course of the study, 409 study participants had at least one serious (grade 4) side effect while on treatment. There were 176 deaths during the course of the study, but none were determined to be due to a side effect of treatment. Overall, there were no differences in the rates of side effects or deaths by race or gender.

There were differences in the rates of specific side effects. Women were more likely than men to develop serious anemia, a red blood cell abnormality that can result in significant fatigue. Though the majority of the participants were on regimens that contained zidovudine (found in Retrovir, Combivir and Trizivir)—a known cause of anemia—an analysis by the study investigators revealed that use of this drug was not responsible for the higher anemia rates.

Black participants were more likely than whites or Hispanics to experience serious kidney and heart disease problems during the study. Dr. Tedaldi’s team, however, points out that this may reflect the higher rates of both conditions among blacks in general and that antiretroviral treatment may be exacerbating the risk. Also, because data on smoking and cholesterol were not collected, it was not possible to determine what impact these heart disease risk factors may have played.

Another side effect more common among black men in the study was psychiatric disorders. And while efavirenz (found in Sustiva and Atripla) is generally known for its central nervous system side effects, psychiatric problems were no more common among black men receiving efavirenz compared with those taking Viramune (nevirapine).

The FIRST study suffered from some limitations, notably the lack of baseline information on factors like smoking and the fact that black participants were more likely than whites to start treatment with lower CD4 counts, which can increase the risk for certain side effects. However, Dr. Tidaldi and her fellow authors still offered the conclusion that physicians with diverse patient caseloads should be aware of the differences found in this study when offering antiretroviral treatment.