Rigorous analysis of study data has upheld the finding from a 2006 report that black people with HIV who didn’t adhere to their regimen were more likely to fail treatment than their non-adherent white counterparts. The report in the December 15th edition of the Journal of Acquired Immune Deficiency Syndromes also found that quality of life was an independent predictor of treatment failure in the study, though it could not explain the difference between races.
The perplexing results arose from US-based clinical trial ACTG A5095, which compared the efficacy of three protease inhibitor-sparing first-line regimens: a three-NRTI regimen versus a two NRTI plus NNRTI regimen versus a three NRTI plus NNRTI regimen. Due to virologic inferiority, the three-NRTI arm was stopped prematurely in 2003. The two remaining NNRTI regimens continued and showed no significant difference in virologic response through a median follow-up of three years. Researchers interpreted the results of the trial as evidence that adding a fourth drug to a regimen does not improve efficacy.
Subgroup analysis of trial data revealed racial differences: black participants were 66% more likely to experience virologic failure than their white counterparts. Researchers also observed a significant interaction between race and self-reported adherence. These results, they stated, suggested that blacks who reported missing doses had a significantly shorter time to virologic failure than non-adherent whites. There are few other studies exploring race and virologic failure and their results are conflicting.
To investigate the link further, Schackman and colleagues revisited the original study data on adherence. During the three-year trial, participants regularly completed a self-administered questionnaire that surveyed for four adherence parameters: any missed doses during the past four days, any missed dose during the previous weekend, any missed dose during the previous month, and never missing a dose. Participants were classified as non-adherent if they reported missing a single dose during the time period in question.
In the initial 2006 analysis, researchers analysed the four-day measure of adherence. They found that virologic failure was associated with nonadherence at week twelve among blacks but not whites. Non-adherent black participants had an estimated cumulative probability of failure by week 144 of 53%, compared with 25% for adherent blacks. White participants, whether adherent or non-adherent, had a probability of 20%.
In the extended analysis, researchers evaluated the interaction using the other three adherence measures (past weekend, past month, and ever). Analysis with these other parameters yielded similar results supporting an interaction between race and adherence in association with virologic failure. The probability of virologic failure among non-adherent blacks ranged from 41% to 57%, depending on the adherence measure used. For adherent blacks, the probability ranged from 22% to 27%. The difference for each adherence measure was statistically significant. Non-adherent whites had a probability of failure from 11% to 24%, compared with the 16% to 21% probability for adherent whites.
In an attempt to better define this interaction of race and adherence, researchers also evaluated quality of life (QOL) among trial participants. Participants were asked to rate their health on a 0-to-100 scale, with 100 representing best possible health. Mean QOL increased from 73.0 at baseline to 83.3 at week 144. The distribution of scores varied with neither four-day adherence nor race. However, using week twelve data, QOL scores were associated with virologic failure. Participants with QOL scores less than 75 had a 2.18 times higher risk of virologic failure than participants with a score of 90 or higher. QOL scores from 75 to 89 were associated with an 1.61-fold higher risk.
QOL was an independent indicator of virologic failure. When observed over time and adjusted for four-day adherence, participants with a QOL score of less than 75 or between 75 and 89 had more than twice the risk of virologic failure of participants with a QOL score of at least 90. There was no significant interaction with adherence or race in this association of QOL and virologic failure. The researchers note that this simple rating scale may be a clinically effective tool for identifying patients at risk of failing treatment.
To account for their findings on race, adherence and virologic failure, the researchers offered two possible explanations. First, they acknowledge that their adherence measures may have missed some racial difference in adherence patterns, such as underreporting of missed doses or reporting interruption as a missed dose. Alternatively, the researchers hypothesise that the association between adherence and virologic failure varies with race due to genetic differences.
Schackman BR et al. Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy. J Acquir Immune Defic Syndr 46:547 – 554, 2007.