Lipodystrophy is an alteration of fat metabolism that commonly affects HIV-1 positive patients treated with antiretroviral therapy (ART). The facial area is most commonly affected by peripheral lipoatrophy, thus becoming a social stigma related to chronic HIV. Several treatments have been proposed, such as modification of diet, lifestyle and both surgical and nonsurgical procedures. The goal of our systematic review is to examine published clinical studies involving the use of polyacrylamide filler for the treatment of HIV FLA, and to provide evidence-based recommendations based on published efficacy and safety data. Our research was performed on published literature until April 2021. Polyacrylamide gel is a volumetric gel that has been proven stable, nontoxic, nonallergenic, nonembryotoxic and nonabsorbable. Poly-l-lactic acid (PLA) is a biocompatible, biodegradable, synthetic polymer derived from lactic acid. We believe it is essential to draft a pre- and post-injection and operative protocol to define an even setting for the clinical condition. It is desirable that such specifications are included in a large randomized controlled trial and the follow up is longer than the studies that we found, because as we have seen in the literature there are reported adverse events even 3 or 5 years after the injections.