['Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown.', 'This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later.', 'Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression.', 'We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time.'] Is self-reported body fat change in HIV-infected men a marker of decline in physical health-related quality of life with aging , independent of co-morbidity?