BackgroundAs infection with the Human Immunodeficiency Virus (HIV) has evolved to a chronic disease, perceived health-related quality of life (HRQoL) is becoming a prominent and important patient-reported outcome measure in HIV care. Literature discusses different factors influencing HRQoL in this population, however, currently no consensus exists about the main determinants. In this review a clear, up-to-date overview of the determinants influencing HRQOL among people living with HIV is provided.MethodsAll studies published before July 2013 that identified determinants of HRQoL among people living with HIV in high-income countries, were considered in this narrative review. PubMed, Web of Science and The Cochrane Library were consulted using the keywords ‘determinants’, ‘quality of life’, ‘HIV’ and ‘AIDS’. To be included, studies should have reported overall health and/or physical/mental health scores on a validated instrument and performed multivariable regression analyses to identify determinants that independently influence perceived HRQoL.ResultsIn total, 49 studies were included for further analysis and they used a variety of HRQoL instruments: Medical Outcomes Study Short Form-36 or variants, Medical Outcomes Study-HIV, HIV Cost and Services Utilization Study measure, Multidimensional Quality of Life Questionnaire, HIV targeted quality of life instrument, Functional Assessment of Human Immunodeficiency Virus Infection, HIV Overview of Problems Evaluation System, EuroQol, Fanning Quality of Life scale, Health Index and PROQOL-HIV. In this review, the discussed determinants were thematically divided into socio-demographic, clinical, psychological and behavioural factors. Employment, immunological status, presence of symptoms, depression, social support and adherence to antiretroviral therapy were most frequently and consistently reported to be associated with HRQoL among people living with HIV.ConclusionsHRQoL among people living with HIV is influenced by several determinants. These determinants independently, but simultaneously impact perceived HRQoL. Most HRQoL instruments do not capture all key determinants. We recommend that the choice for an instrument should depend on the purpose of the HRQoL assessment.Electronic supplementary materialThe online version of this article (doi:10.1186/2049-3258-72-40) contains supplementary material, which is available to authorized users.