BRIEF REPORT:CLINICAL SCIENCE Lipid and Apoprotein Proﬁle in HIV-1–Infected Patients After CD4-Guided Treatment Interruption Elena Seoane, MD, PhD,* Salvador Resino, PhD,*† Dariela Micheloud, MD, PhD,* Ana Moreno, MD,‡ Juan C. L. Bernaldo de Quiros, MD, PhD,§ Raquel Lorente,* Rafael Rubio, MD, PhD, k Juan Gonzalez, MD, PhD,¶ Federico Pulido, MD, PhD, k Jose ´ R. Arribas, MD, PhD,¶ Santiago Moreno, MD, PhD,‡ and Ma ´. Mun ˜oz-Ferna ´ndez, MD, PhD* Objectives: The aims of the present study were to determine if metabolic abnormalities and cytokine derangements are modiﬁed in HIV-1–infected patients after 12 months on treatment interruption (TI). Design: The design of this study was prospective randomized study. Methods: Longitudinal multicenter study in HIV-1–infected patients with a 12-month follow-up. Patients on stable highly active antiretroviral therapy, with CD4 count .600/mL and HIV RNA ,50 copies/mL for at least 6 months, were randomized to interrupt therapy or continue ongoing highly active antiretroviral therapy. Lipids (total cholesterol, triglycerides), apoproteins (A1, B, and E), and adipocytokines (leptin, adiponectin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, Interleukin-6, Interleukin-8, and tumor necrosis factor-a) were measured at baseline and at month 12. Multiplex suspension bead array immunoassay was performed using the Luminex 100 analyzer to identify protein expression in plasma. Results: Patients who underwent TI (n = 19) had a signiﬁcant decrease in median cholesterol levels (P , 0.001), while median triglyceride levels remained unchanged. There was a signiﬁcant decrease in Apo-A1 levels (P = 0.048) and Apo-B levels (P , 0.001) and an increase in tumor necrosis factor-a levels (P = 0.034). Given the greater decrease in Apo-B, the ratio Apo-A1/Apo-B increased after 12 months of TI (from 3.4 to 5.1, P = 0.008). We did not ﬁnd signiﬁcant variations in leptin or adiponectin levels. In patients who continued on highly active antiretroviral therapy (n = 18), there were no signiﬁcant changes in any of the measured parameters. Conclusion: The lipid proﬁle and apoproteins levels change toward a less atherogenic proﬁle after TI, arguing against a lipid-mediated mechanism to explain the increased cardiovascular risk in patients who interrupt treatment. Key Words: HIV, treatment interruption, cardiovascular risk, adipocytokines, apoproteins (J Acquir Immune Deﬁc Syndr 2008;48:455–459) INTRODUCTION Treatment interruption (TI) has been considered as a potentially useful strategy for limiting exposure to antiretroviral therapy (ART) and thus decreases some of the disadvantages of long-term treatment. Results of clinical studies performed to test the utility of TI have offered controversial results. Several controlled and uncontrolled studies have shown that ART might be safely interrupted for varying periods of time among healthy patients with controlled viremia and high CD4+ cell counts. 1–3 Recent reports, however, have found that patients undergoing TI were at signiﬁcantly higher risk of severe clinical events and death than those continuing ART. 4–6 The most unexpected ﬁnding to date of clinical trials of CD4-guided TI has been the excess occurrence and death rate associated with nonopportunistic complications in the large Stragegies for Management of Antiretroviral Theraphy (SMART) trial. 4 Overall rate of cardiovascular, renal, or hepatic disease in patients who interrupted therapy exceeded any prediction because these events are usually considered to be drug-related adverse events, and patients who discontinue therapy should be relatively protected from them. The higher rate of cardiovascular disease in patients on TI was particularly intriguing. Previous reports have found a relationship between dyslipidemia associated with antire- troviral drugs and the occurrence of cardiovascular events. 7,8 No data are provided in the SMART trial regarding the evolution of lipids in patients who interrupted therapy. We present herein the results of a small, randomized clinical trial Received for publication August 16, 2007; accepted March 13, 2008. From the *Laboratorio de Inmuno-Biologı ´a Molecular, Hospital General Universitario ‘‘Gregorio Maran ˜o ´n,’’ Madrid, Spain; †Unidad de Inves- tigacio ´n, Instituto de Salud Carlos III, Majadahonda, Spain; ‡Enfermedades Infecciosas, Hospital Universitario ‘‘Ramo ´n y Cajal,’’ Madrid, Spain; §Enfermedades Infecciosas/VIH, Hospital Universitario ‘‘Gregorio Maran ˜o ´n,’’ Madrid, Spain; k Unidad de Infeccio ´ n VIH, Hospital Universitario ‘‘12 de Octubre,’’ Madrid, Spain; and the {Enfermedades Infecciosas, Hospital Universitario ‘‘La Paz,’’ Madrid, Spain. Supported by grants from Fondos de Investigacio ´ n Sanitaria del Ministerio de Sanidad y Consumo (PI052476, PI061479); Red Tema ´tica Cooperativa de Investigacion ´ en SIDA (RID) RD06-0006-0035; FIPSE (36514/05, 24534/05), Fundacio ´n Caja Navarra, and Comunidad de Madrid (S- SAL-0159-2006) to M.A ´ . M-F. From Fondos de Investigacio ´n Sanitaria (FIS) (PI052411, PI07/90201) and Fundacio ´n para la Investigacio ´n y la Prevencio ´n del SIDA en Espan ˜a (FIPSE) (36650/07) to S.R. The authors do not have commercial or other associations that might pose a conﬂict of interest. M. A. M. F. and S. M. have equally contributed to this work. Correspondence to: M a A ´ ngeles Mun ˜oz-Ferna ´ndez, MD, PhD, Laboratorio de Inmuno-Biologı ´a Molecular, Hospital General Universitario ‘‘Gregorio Maran ˜o ´ n,’’ C/Doctor Esquerdo 46, 28007, Madrid, Spain (e-mail: mmunoz.hgugm@salud.madrid.org). Copyright Ó 2008 by Lippincott Williams & Wilkins J Acquir Immune Deﬁc Syndr  Volume 48, Number 4, August 1, 2008 455 Copyright © 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.