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Background: The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented., Methods: This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy., Results: After a median follow-up of 23.2 months (interquartile range 22.3-23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15-2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33-1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22-0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28-1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5-307.4]; P=0.006) were significantly associated with lipohypertrophy., Conclusions: Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART.