Cross-sectional studies report that pain in ambulatory HIV-infected individuals is frequent and often undermanaged. Expanding access to HIV treatment in developing countries means that infected individuals are living longer, but there is a dearth of pain-directed studies from developing countries that describe the progression of pain and its treatment over any period of time. The aim of this study was to characterize the progression of pain and its treatment over a 6-month period in 92 ambulatory HIV-positive patients attending an outpatient clinic in Johannesburg, South Africa. We used the Wisconsin Brief Pain Questionnaire to assess changes in pain intensity, pain sites, pain interference, and pain treatment. At visit 1, pain was present in 78 of 92 patients (85%). Of the 78 patients with pain, 67 had moderate or severe pain (86%) and pain affected two or more body sites simultaneously in 57 of these patients (73%). After 6 months, pain prevalence still was high, but had fallen to 50 patients (54%). Of the patients with pain at visit 2, the proportion with moderate or severe pain (82%), or two or more pain sites (62%) had decreased. Analgesic use was low at both time points (5% and 25% analgesic use at visit 1 and 2, respectively). Despite the high pain burden, pain interference in daily activities was very low across the period assessed. The burden of pain in this cohort of ambulatory HIV-positive patients was high, but there were significant reductions in pain burden over time.