The syndemics theory seeks to understand the effect of multiple synergic problems in promoting poor health outcomes. To disentangle which and how syndemic conditions affect the quality of life (QoL) may be important to improve well-being of people living with HIV/AIDS (PLWHA). This study evaluates the association between syndemic conditions and QoL among PLWHA. We performed a secondary analysis using data obtained between 2014 and 2017 among PLWHA under care in Rio de Janeiro, Brazil. The outcomes were the six QoL domains (physical, psychological, level of independence, social relationships, environmental, and spirituality) measured through the World Health Organization Quality of Life in HIV infection scale, abbreviated version (WHOQOL-HIV-BREF). The independent variables were demographic and clinical characteristics, syndemic conditions (binge drinking, compulsive sexual behavior, polysubstance use, intimate partner violence, and depression), and syndemics (two or more syndemic conditions simultaneously). Bivariate analysis (-test and ANOVA) and linear regressions were performed for each quality-of-life domain. The analytical sample comprised 1530 participants, mostly male at birth (64%) and with median age of 43 years. The syndemic conditions most frequently observed were binge drinking (56%), IPV (13%), and depression (9%). Both individual syndemic conditions and syndemics were associated with worse QoL. In the multivariate analysis, positive screening for depression was associated with worse QoL in all domains. Polysubstance users presented worse QoL at social and environmental domains. Intimate partner violence was associated with worse QoL at environment domain while binge drinking was associated with worse scores in the physical domain. The presence of syndemics increased the likelihood of worse scores in the psychological, social, and environment domains. Our study expands the understanding of QoL in PLWHA, as it considers a holistic/integral, multifactorial, and synergistic approach to the determinants of QoL. Seeking strategies that target syndemics may be important to improve patient-centered outcomes in health.Abbreviations: HIV/AIDS: human immunodeficiency virus/acquired immunodeficiency syndromeWHO: World Health OrganizationQoL: quality of lifeHRQoL: health-related quality of lifePLWHA: people living with HIV/AIDScART: combined antiretroviral therapyIPV: intimate partner violenceINI/FIOCRUZ: Evandro Chagas National Institute of Infectious DiseasesOswaldo Cruz FoundationSRH: self-rated healthVL: viral loadCD4: CD4 cell countNIAAA: National Institute on Alcohol Abuse and AlcoholismCSBcompulsive sexual behaviorWHO-ASSIST: alcoholsmoking and substance involvement screening test developed by the World Health OrganizationPHQ-2: Patient Health Questionnaire-2.

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