Despite this, there did not appear to be any relation between skin induration and the amount of product injected in our study; however, the maximum amount injected into each cheek was only 3 mL. The occurrence of skin induration was spread evenly among study participants, with only three patients developing skin indurations twice during the study period. Six patients who did not present with skin indurations at the 6-week post-treatment consultation

went on to develop round subcutaneous papules in the following 12 months. In some cases it appeared as if a capsule had formed around the product over time. The papules did not appear to be granulomatous inflammatory reactions. The most common Venetoclax chemical structure adverse event associated with polylactic acid injections is subcutaneous papule formation [10] and, similar to our experience, papule formation as early as the first month and up to 12 months later has been described [20], as well as late-onset inflammatory nodules [21]. Four patients in our study, who found the papules to be bothersome, were treated with hyaluronidase injections at

the 24-month visit to remove the papules. In all four cases, the papules dissolved completely within a few hours of a single treatment with hyaluronidase. Given that many of the soft-tissue fillers available for treatment of lipoatrophy can result in papule formation [9], hyaluronic acid Wnt inhibitor preparations offer the added advantage of being easily dissolved with hyaluronidase should any complications occur [22]. As a comparison, in a long-term study where polylactic acid was used to treat HIV lipoatrophy and subcutaneous papules were the most common adverse event, subcision was used to remove papules, and although there was an improvement, complete resolution was not attained [10]. After injections of Restylane SubQ, skin indurations

have also been treated by partial or complete aspiration of the implant (performed Diflunisal as late as 12 months after initial treatment) which led to resolution [13]. Biodegradable soft-tissue fillers have a lower incidence of adverse events compared with permanent fillers [9] and are a preferable treatment given that the recovery process of adipose tissue continues after ART has been modified [3,4], which could result in an overcorrection of the lipoatrophic area if permanent fillers are used. Two biodegradable soft-tissue fillers, Radiesse (calcium hydroxyapatite) and Sculptra (polylactic acid), are to date the only FDA approved treatments for lipoatrophy in HIV-positive patients. Radiesse is well tolerated with few adverse events; however, long-term data for use of this product in HIV-positive patients is lacking [23]. Polylactic acid appears to be the material most often used in the treatment of HIV-related facial fat atrophy.