Quality of life in the GRACE study
Polly Clayden, HIV i-Base
One study that was designed to enroll and evaluate a high proportion of women was the Gender, Race And Clinical Experience (GRACE) open label trial of darunavir/ritonavir (DRV/r)-based regimens. 
This trial also included a high proportion of black participants and everyone was treatment experienced.
Of the 429 people enrolled, 66.9% were women, 61.5% black, 22.4% Hispanic and 15.2% white.
This trial found significant differences in discontinuations with substantially more women than men discontinuing for reasons other than virological failure, 32.8% vs 23.3%, p=0.042. A higher proportion of black participants did not complete the study compared to hispanic or white participants.
Intent-to-treat analysis showed 50.9% of women compared to 58.5% men had viral load <50 copies/mL at week 48, p=0.067. In the analysis that censored the patients that discontinued for reasons other than virological failure, the response rate was 73.0 in women compared to 73.5% in men, p=0.44.
Health-related quality of life (HRQoL) measures are used to quantify the physical and mental aspects of being HIV-positive that can have an impact on someones overall well being. Several studies have demonstrated a correlation between HRQoL and survival of people with HIV.
Judith Feinberg reported the HRQoL results by sex and race from the GRACE study. 
HRQoL was measured by the validated Functional Assessment of HIV Infection (FAHI) questionnaire. This was completed at baseline, at weeks 4, 12, 24 and 48 (or when a participant left the study, if they discontinued early).
FAHI consists of 47 questions to measure aspects of physical, emotional, functional and social well-being, and cognitive functioning. The total score (range 0-176, higher scores better) is calculated as the sum of the scores from the five subscales.
The investigators also conducted some post hoc analyses to look at factors associated with an improvement in scores. Analyses were performed on the observed population.
The total FAHI scores at baseline were 118.1 (n=423) overall, 116.8 (n=283) women and 120.8 (n=140) men. They were 119.5 (n=261), 114.1 (n=94) and 119.5 (n=64) for black, Hispanic and white ethnicity respectively.
The overall score of the total population improved significantly by week 4, with a mean increase from baseline of almost 30%, p<0.05. By week 12, near maximum changes of just over 70% were achieved overall and these remained consistent through to week 24 and week 46. Patterns of improvement were similar for men and women, but improvements were greater for women, with over 80% at 48 weeks, than men whose improvement was less than 60%. Black participants also demonstrated greater improvement in total FAHI score that either Hispanic or white participants.
The investigators found that patients with lower baseline HRQoL scores were significantly more likely to discontinue the study than those who scored higher, p=0.044. They noted that this is the first time lower baseline HRQoL has predicted study discontinuations.
In order to assess whether the QoL improvement was due to participants with lower HRQoL scores discontinuing early, the investigators conducted a sensitivity analysis evaluating only those who completed the study. They found, the baseline value with patients who discontinued excluded was 120.1 and the total FAHI score still improved to the same extent from baseline to 48 weeks compared to the total study population, p<0.05.
Multivariate analysis identified four factors that were significantly associated with the improvement in FAHI score over 48 weeks: lower baseline FAHI score, p<0.001; lower baseline CD$ count, p=0.0077; virological response, p=0.0045 and the timepoint of analysis (total FAHI score increased over time. Neither sex nor ethnicity was independently found to be associated.
The investigators concluded that HRQoL improved significantly for the study population overall and that sensitivity analysis suggests that this was not due to people with low HRQoL scores discontinuing the trial.
The largest improvements in total FAHI scores were seen in women and black participants, despite these two groups having lower virological response rates and higher discontinuation rates when compared to men and to Hispanic and white patients, respectively.
In future, it may be possible to identify patients with a higher risk of discontinuation based on their baseline HRQoL scores; these patients could then be more closely monitored and supported, potentially improving retention.
These are interesting findings and GRACE must be applauded for conducting this study in harder to reach trial populations.
Gender sub-analyses from ARTEMIS and CASTLE trials also show similar virological response between women and men.
- Currier J et al. Sex-based outcomes of a single-group trial. Annals of Internal Medicine. Volume 153. Number 6. 21 September 2010.
- Feinburg J et al. Association of sex and race with health-related quality of life in patients treated with darunavir/ritonavir-based therapy in the GRACE trial. 1st International Workshop on HIV and Women. 1011 January 2011, Washington. Oral abstract O_15.