The Exception to the Rule: Discordant Responses to Antiretroviral Therapy
October 2011 - After starting antiretroviral therapy (ART), HIV in the blood typically falls to undetectable levels, leading to increases in CD4 cells that reflect improvements in the immune system. However, some people do not follow this pattern. Instead, they continue to have low levels of virus despite increases in their CD4 cells, or they have minimal changes in their CD4 levels despite having undetectable virus. These are known as "discordant" responses to ART and have been well described in Western settings.
Researchers studied discordant responses among 1,121 Asian and 1,036 Australian patients within the Asia-Pacific HIV Observational Database (APHOD).1 After 12 months of ART, 19 percent of patients had undetectable virus but limited improvements in CD4 levels, and 12 percent had good CD4 recovery but low levels of virus. This pattern of discordant response was similar at 24 months after ART.
In comparison to those with a typical pattern of response to ART, the 12 percent of patients who had persistently detectable HIV in their blood also had a significantly higher risk of disease progression (i.e., either death or a new AIDS-defining illness). The 19 percent of patients with poor CD4 responses were more likely to be male, have been diagnosed with AIDS before starting ART, and have used the antiretroviral drug didanosine in their treatment regimen. Overall, patients who started ART when their CD4 levels were higher and had comparatively lower virus levels in their blood (i.e., <50,000 copies/ml) were more likely to have a better immune system response.
These results were similar to levels of discordance reported in patients in the U.S. The study findings emphasize that viral load testing is a more accurate indicator than CD4 levels of whether patients are responding to ART. They also raise the concern that assessing treatment failure on the basis of the CD4 level alone can lead to unnecessary ART regimen switches in those patients with discordant responses.
1. Choi JY, Zhou J, Giles M, Broom J, Templeton DJ, Law MG, Chaiwarith R, Tanuma J, for Asia-Pacific HIV Observational Database. Predictors and outcomes of HIV-infected antiretroviral-naive patients with discordant responses to combination antiretroviral treatment in Asian and Australian populations: results from APHOD. J Acquir Immune Defic Syndr. 2011 May 1;57(1):e13-5.