Lipodystrophy is one of the foremost concerns among the HIV-positive population, and is often associated with psychosocial disorders. We evaluated the clinical efficacy of facial infiltrations with autologous fat, polylactic acid, and polyacrylamide gel using clinical inspection and facial photographs (ordinal scale). Additionally, we assessed the safety of the infiltration techniques and determined changes in patient satisfaction, emotional status, and quality of life. Evaluations were made at 48- and 96-week follow-up visits. This paper presents the 48-week follow-up results. The current analysis includes 138 patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel groups, respectively. At baseline, almost 50% of the patients (67/138) presented grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these advanced grades (no patients from the polyacrylamide group). A new round of infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and 8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious adverse events were detected with any of the substances. Patient satisfaction and quality of life improved significantly in all three groups. Infiltrations with autologous fat, polylactic acid, or polyacrylamide gel appear to be an effective and safe alternative to repair facial lipoatrophy, at least up to 48 weeks, significantly improving patient quality of life. Similar results were observed for all degrees of severity and between genders. Polyacrylamide gel provided the longest lasting benefits. © Mary Ann Liebert, Inc.