We have presented a thorough analysis of observational HRQL data in a single cohort using established qualitative methods and the new psychometric instrument, PROQOL-HIV. This is the first comprehensive study of HRQL in Western Australia since the HIV epidemic began thirty years ago. The results from the survey, supported by the interview material, demonstrate that HIV influences HRQL across the spectrum of biological, social and psychological domains that comprise the complex continuum of measures of health . In particular, people reporting: unemployment, depression, and a higher frequency of symptoms, particularly those impacting negatively on sexual expression, scored a poorer quality of life overall, independently of other factors and regardless of ART status. Interview respondents struggling with romantic relationships described feelings of loss around cessation of sexual practices relinquished to prevent transmission; opportunities to engage in sexual activity without the burden of disclosure; fear of rejection and the potential for transmission despite use of safer sex strategies. Accordingly, the novel instrument has captured a dimension of HIV-related stigma, by way of an individual’s fear of disclosing their HIV serostatus and/or transmitting the infection that clearly results in emotional distress. Therefore, although the HIV/AIDS-Targeted Quality of Life Instrument (HAT-QOL) has a dimension for disclosure concerns , the PROQOL–HIV questionnaire goes a step further and juxtaposes anxiety about transmitting the infection with fear of disclosure.
In concordance with Lee’s research , the survey showed that feelings of stigma were heightened in those more recently diagnosed in contrast with those who had a longer history of HIV infection. These included the small number of patients infected via IDU who had a relatively long time since diagnosis (mean=12 years) and might be expected to experience compound stigma related to their membership of another marginalised group . However, more than half of survey respondents expressing stigma concerns had been on therapy for over three years; and the interviews highlighted persistent concern that HIV-related stigma negatively affected relationships and employment opportunities, consistent with other studies [11, 12, 32, 33]. Courtenay-Quirk and colleagues  found that avoidant coping strategies, anxiety, loneliness, depressive symptoms, and suicidal ideation were associated with HIV-related stigma in a community of HIV-positive men; and Holzemer  showed that stigma had a negative effect on quality of life independently of HIV-related symptoms and severity of illness. More recently Hutton and others , using the Personal Well Being Index  reported that stigma impacted negatively on subjective well-being in PLWH in Australia and the USA by way of perceived unsupportive (hurtful) social interactions.
While HIV-related stigma has been associated with depression , and specific concerns such as serostatus disclosure fears and transmission anxiety have been reported [11, 30, 39], we could not find evidence in the literature suggesting that transmission anxiety per se is a specific stressor in HIV-related depression and contagion fears appear more commonly addressed in uninfected individuals [40, 41]. Cognitive behavioural interventions have been trialed to decrease HIV-related stigma and a recent study reported that an intervention improving personal control via a sense of mastery and increased social support may be beneficial in reducing stigma in people with depressive symptoms [38, 40].
It was somewhat surprising then that reported depression did not correlate with the stigma domain in our study, and it is concerning that the fear of infecting others, which in some individuals resulted in avoidant behaviour out of proportion to risk, may not be uncovered in the course of clinical consultations. Since stigma may be nuanced by its various associations with sex, gender, death and ethnicity  and deeply internalised  it could be examined by assessing the limitations that people place upon their lives as a result of the anxiety.
A number of demographic factors contributed to a diminished perception of HRQL among the respondents to the interviews and the questionnaires. Notably, people living alone cited restricted intimate and/or social relationships, although whether this was as a result of self withdrawal or inhibition with regard to disclosing HIV status, or some other reason, is not clear. Older age and longer duration of HIV were associated with an improvement in HRQL, as observed by others . In particular, older Caucasians were less troubled by health concerns related to regular CD4 and viral load monitoring and progression of the disease, perhaps reflecting their adjustment to diagnosis, better knowledge of the disease and/or greater confidence in the treatment, reinforced by successful treatment outcomes. However, unemployment and disability resulted in diminished HRQL regardless of age and the interviews revealed a picture of social isolation and physical discomfort not necessarily directly attributable to HIV disease.
People on PIs reported more symptoms, especially gastrointestinal, and more tablets overall compared with those on NNRTI regimens. This translated into greater treatment impact, but not into reduced HRQL overall, most likely because of improvements in overall physical health and perhaps psychosocial adjustments associated with the longer average duration of ART and time since diagnosis. The level of adherence in our patients was higher than in the other cohorts in the international study , perhaps reflecting once daily dosing, but we did not find a direct relationship between adherence and global HRQL. However, non-adherence to ART remained predictive of lower treatment impact scores over and above treatment choice and viral load. This finding suggests that the benefits of treatment were not perceived by non-adherent participants.
The study had been sufficiently powered to show significant site-specific effects of covariates on HRQL domains. However, the fact that the combined covariate sets explained only 55% in the PROQOL-HIV score variation suggests the total score may incorporate facets additional to quality of life specifically related to HIV, and is assessing additional information from a patient perspective that cannot be adequately inferred from the usual sociodemographic or biological variables. This finding concurs with Wilson’s  conceptual model suggesting that total HRQL is substantially impacted by some hard-to-measure factors relating to personality, which may contribute to resilience and coping.
There were limitations to our study. Cross-sectional design is less robust than longitudinal measurement where responses are measured over a period of time; however the qualitative component strengthens the internal validity of the study. The closed-ended format of the questionnaires did not accommodate explanations, but the questions were derived from the themes gathered in the interviews where patients qualified their responses to semi-directive questions freely.
The development of PROQOL-HIV, has allowed the measurement of dimensions not assessed in the past. Application in our local setting has demonstrated that the instrument will provide a useful tool in cohort analysis to assess health-related quality of life in general, and those that result from treatment interventions in particular. Inclusion of a stigma domain adds further utility since it is evident that stigma is a persistent feature of HIV infection and may result in emotional harm, particularly in those less resilient. The multiple nuances of stigma should be disentangled in future research in order to develop suitable interventions. In conclusion, disease-specific HRQL instruments can bring additional information to the classical criteria for evaluating clinical outcomes and should be part of studies evaluating health policy and treatment strategies .
The study was conducted at Royal Perth Hospital in Western Australia and was supported by the Assistance Publique–Hopitaux de Paris (AP-HP), GILEAD Sciences, and Sidaction.