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Purpose: We selected and evaluated a comprehensive set of themes that encompass health-related quality of life (HRQOL) among HIV patients, which enables clinicians to tailor care to individual needs, follow changes over time and quantify returns on health care investments and interventions., Methods: HIV patients (N = 250) of two Dutch HIV clinics were invited to complete an online survey comprised of a set of (adaptations of) validated questionnaires measuring eight themes, including general health (SF-12), stigma (short stigma scale), social support (SSL12-I), self-esteem (SISE), sexuality problems, anxiety and depression (HADS), sleeping difficulties (SCL90-Sleep) and perceived side-effects., Results: Findings from 170 (response rate 68%) patients (Male = 159, 94.1%) showed that questionnaires had high internal consistency, and most themes significantly correlated (r's .21 to - .69, p < .05) in the expected directions. Exploring cut-off scores shows that a significant proportion of patients score outside of the desired range on single themes (between 16.0 and 73.1%), and many patients on multiple themes simultaneously (8.9% on 5 or more themes). Regression analysis showed that social support, self-esteem and sexuality problems were associated with general health (R = .48, R 2  = .23, F(4,145) = 10.57, p < .001); adding anxiety and depression, sleeping difficulties and perceived side-effects explained 51.2% of the variance in total (R = .72, ∆R 2  = .29, F(3, 142) = 27.82, p < .001)., Conclusions: We succeeded in developing a questionnaire that comprehensively assesses HRQOL. HRQOL of the majority of Dutch HIV patients could be improved. The themes strongly influenced each other, therefore insights into any of the themes could inform interventions to improve HRQOL, and increase attention to these themes in routine consultations between patients and health care professionals.