Background Musculoskeletal symptoms in people living with HIV (PLWH) such as pain, joint stiffness, and fatigue are commonly reported. Prevalence rates of up to 45%, 79% and 88% respectively have been reported. However, very little is known about differences in prevalence and impact of musculoskeletal symptoms on physical functioning and quality of life of PLWH on effective combined antiretroviral treatment (cART) in high and low-resource settings. Methods A cross-sectional study of PLWH on effective cART enrolled from two large urban clinics in the UK and Zambia was conducted in 2016. Eligible participants had no history of trauma to the joints within 4 weeks of recruitment, or documented evidence of previous rheumatic disease. Current musculoskeletal symptoms, functional ability, and health-related quality of life were evaluated using the health assessment (HAQ) and quality-of-life short form (SF-36) self-reported questionnaires. Results 214 patients were enrolled (108:UK and 106:Zambia). Participants from Zambia were younger (47 vs 44 years) and had significantly lower CD4 counts (640 vs 439 cells/mL p = 0.018) compared to those from the UK, while the UK group had lived with HIV longer (11 vs 6 years; p<0.001) and reported more comorbidities than the Zambian group (66% vs 26%; p<0.001). Musculoskeletal pain was common in both groups (UK:69% vs Zambia:61% p = 0.263) but no significant differences in physical functional capacity between the groups were observed. However, the UK group had significantly worse quality of life measurements (general health, vitality, mental health, emotional, and social functioning) associated with musculoskeletal symptoms compared to the Zambian group (p<0.001). Conclusions Musculoskeletal symptoms in PLWH from both the UK and Zambia were common. PLWH in the UK reported worse quality of life measures associated with musculoskeletal symptoms compared to those in Zambia, suggesting that factors such as mental health, patient expectations and multimorbidity might play a role in determining well-being and quality of life of PLWH with musculoskeletal symptoms.

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