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Evaluate the effect of antiretroviral therapy (ART) on South African HIV patients’ economic well being, as indicated by symptoms, normal activities, employment, and external support, during the first 5 years on treatment.Prospective cohort study of 879 adult patients at public or nongovernmental clinics enrolled before ART initiation or on ART less than 6 months and followed for 5.5 years or less. Patients were interviewed during routine clinic visits. Outcomes were estimated using population-averaged logistic regression and reported as proportions of the cohort experiencing outcomes by duration on ART.For patients remaining in care, outcomes improved continuously and substantially, with all differences between baseline and 5 years statistically significant (P < 0.05) and continued significant improvement between year 3 and year 5. The probability of reporting pain last week fell from 69% during the three months before starting ART to 17% after 5 years on ART and fatigue from 62 to 7%. The probability of not being able to perform normal activities in the previous week fell from 47 to 5% and of being employed increased from 32 to 44%; difficulty with job performance among those employed fell from 56 to 6%. As health improved, the probability of relying on a caretaker declined from 81 to less than 1%, and receipt of a disability grant, which initially increased, fell slightly over time on ART.Results from one of the longest prospective cohorts tracking economic outcomes of HIV treatment in Africa suggest continuous improvement during the first 5 years on treatment, confirming the sustained economic benefits of providing large-scale treatment.