In the news ... 2008

Sustiva study finds ethnicity,
quality of life predict treatment outcomes

by Paul Dalton
April 1, 2008

A study published in the journal AIDS found that ethnicity, adherence and quality of life measures affected how likely people were to experience failure on a regimen with Sustiva (efavirenz). The analysis from ACTG A5095 adds to a growing sense of unease about Sustiva, particularly in people of African descent.

ACTV A5095 compared two HIV drug regimens: Trizivir (zidovudine /AZT + lamivudine /3TC + abacavir), vs. Sustiva + Combivir (zidovudine + lamivudine) in people taking HIV drugs for the first time. Earlier analysis had found a higher rate of treatment failure in participants of African ancestry. The researchers tried to find out what factors may explain this.

This study looked at over 700 people, who had one or more adherence evaluations during the study. Overall, non-adherence after 12 weeks was a strong predictor of treatment failure. Looking more closely, however, this was only true for participants of African descent and not for whites.

A previous report from this study found no adherence differences between ethnic groups, for people taking Trizivir. However, there was a higher rate of self-reported non-adherence for Africans taking Sustiva in this study. One possible explanation for these higher rates could be more severe side effects, discussed in more detail below. Interestingly, non-adherence resulted in treatment failure more often for people of African descent than whites.

What could explain this curious finding? In theory, non-adherence to a Sustiva regimen should lead to treatment failure equally, regardless of racial or ethnic background. It may be that in addition to more blacks than whites reporting missed doses, there could be different numbers of missed doses. More frequent missed doses increase the chance of resistance developing. The study relied on self reporting to measure adherence, which limits the reliability of the information.

Another possibility has to do with racial differences in how Sustiva is absorbed, distributed and eliminated by the body, called pharmacokinetics. At least one study has found that Africans might break down Sustiva more slowly than other ethnic groups. If people miss a dose of their full regimen, this fact might allow lower levels of Sustiva to persist in the body for longer, creating a greater risk of drug resistance.

Some research, along with numerous anecdotal reports, suggests that people of African descent may experience more severe side effects when taking Sustiva, compared to other ethnic groups. The pharmacokinetic differences explained above might help explain the higher risk of side effects, as more drug could accumulate in a person’s body, raising the risk of side effects. More side effects often lead to adherence problems.

The least surprising finding from this study was the relationship between quality of life and treatment outcomes. Participants were asked to rate their quality of life on a scale of 1–100. People whose scores were below 75 had twice the risk of treatment failure than those with higher scores. Better quality of life is likely to lead to more consistent adherence and better treatment outcomes. Importantly, the researchers looked for and did not find any differences in quality of life measures in different ethnic groups.

Understanding the risk of side effects and factors that affect adherence with HIV drugs is vitally important; even more so for widely used drugs like Sustiva — which is part of the popular fixed-dose combination Atripla. Sustiva is a powerful and often effective HIV treatment. It is also well known to cause side effects, particularly neuro-psychological, like vivid dreaming and depression. African Americans are disproportionally impacted by HIV/AIDS, and tend to be underrepresented in clinical trials of HIV drugs. Research like this may lead to better understanding and use of Sustiva.

The bottom line
This research does not suggest that people, including those of African descent, should stop taking Sustiva. It does point to the importance of good adherence and attention to quality of life. This is true no matter what combination of HIV drugs a person takes. It also highlights the need for more research on the effect of ethnicity on regimens with Sustiva.