CLINICAL TRIALS/CLINICAL STUDIES Immediate versus Delayed Surgical Intervention for Reconstructive Therapy of HIV-Associated Facial Lipoatrophy: A Randomized Open-Label Study Pasquale Narciso, 1 Raffaella Bucciardini, 2 Valerio Tozzi, 1 Rita Bellagamba, 1 Jelena Ivanovic, 1 Marinella Giulianelli, 1 Sabrina Scevola, 1 Antonio Palummieri, 1 Vincenzo Fragola, 2 Maurizio Massella, 2 Luca Fracasso, 3 and Roy De Vita, 3 with additional study participants Paola Pierro, 1 Annamaria Del Maestro, 1 Marco Mirra, 2 and Liliana Weimer 2 Abstract We assessed the safety and efficacy of reconstructive therapy with facial fillers for the treatment of HIV-associated facial lipoatrophy (FLA) through a randomized, controlled, open-label single-center study. A total of 134 HIV-infected patients with severe FLA were randomly assigned to receive immediate (67 patients) or delayed (67 patients) facial injections of poly-l-lactic acid (PLA) or polyacrylamide gel (PAIG). Outcome mea- sures included changes in physician and patient FLA severity scale, adverse events, and changes in health- related quality of life (HRQoL) and anxiety using validated measures. The mean average study follow-up was 27 weeks for the immediate and 25 weeks for the delayed subjects. Adverse events were mild and resolved after a mean of 4 days. Compared to patients randomized to the delayed treatment group, patients assigned to the immediate treatment group had significantly lower physician-rated (0.0 versus 3.0; p < 0.0001) and patient- rated (0.1 versus 1.8; p < 0.0001) FLA severity scores. By contrast, measures exploring HRQoL and anxiety did not show any significant difference between patients randomized to the immediate and deferred groups. Re- constructive therapy with facial fillers was effective and safe and led to significant improvements in FLA severity. However, no significant gains in HRQoL, relational and psychological consequences of body changes, and anxiety-related concerns were observed. Studies should be performed to identify patients who could maximally benefit from filling interventions for FLA. Introduction T he introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV-infected persons has dramatically reduced mortality and morbidity, 1 making health-related quality of life (HRQoL) improvements an important goal of therapy. 2,3 Unfortunately, a significant proportion of patients receiv- ing HAART may develop morphological abnormalities gen- erally termed lipodystrophy syndrome, consisting of either lipoatrophy or visceral fat accumulation, or both. 4–7 Periph- eral fat wasting and lipoatrophy are particularly worrisome since they may stigmatize patients negatively, affecting their lifestyle. 8 Incomplete knowledge of syndrome etiology, pathogene- sis, and evolution has made it difficult to establish suitable therapeutic strategies to confront all aspects related to ab- normal body fat distribution. 9–11 Facial lipoatrophy (FLA) is one of the most distressing and stigmatizing expressions of the antiretroviral-associated lipo- dystrophy syndrome. It may deeply affect the quality of life of patients, rendering them more likely to be identified as HIV positive, thus leading to decreased self-esteem and social withdrawal. 12–14 Despite the improved knowledge on FLA etiology and risk factors, successful medical treatments for the management of this side effect of HIV are still troublesome. 15 Possible interventions include changes in living habits (diet and physical exercise) and HAART modification, such as switching from stavudine or zidovudine to abacavir or teno- fovir. However, FLA reversal after drug switching is gradual, incomplete, and may expose the patient to risks of new 1 National Institute for Infectious Diseases Lazzaro Spallanzani, 00149 Rome, Italy. 2 Department of Drug Research and Evaluation, Istituto Superiore di Sanita ` , Rome, Italy. 3 Regina Elena National Cancer Institute, Rome, Italy. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 25, Number 10, 2009 ª Mary Ann Liebert, Inc. DOI: 10.1089=aid.2009.0029 979