You could be reading the full-text of this article now if you...

If you have access to this article through your institution,
you can view this article in

Potent and Sustained Antiviral Response of Raltegravir-based Highly Active Antiretroviral Therapy in HIV Type 1-infected Children and Adolescents

Briz, Verónica PhD*; León-Leal, Juan A. MD; Palladino, Claudia PhD*; Moreno-Perez, David MD; de Ory, Santiago J. BSc; De José, Ma Isabel MD§; González-Tomé, Ma Isabel MD; Martín, César Gavilán MD; Pocheville, Itziar MD**; Ramos, José T. MD††; Leal, Manuel MD‡‡; Muñoz-Fernández, Ma Ángeles PhD, MD*

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e31824580e8
HIV Reports
Abstract

Background: There are pediatric patients receiving many highly active antiretroviral therapy (HAART) regimens entailing drug resistance mutations that complicate HAART effective therapies.

Methods: This was a multicenter retrospective study of 19 multidrug-resistant children and adolescents enrolled from July 2007 to October 2009. Patients were nonresponders because no reduction in HIV type 1 (HIV-1) RNA to undetectable levels was observed during their previous antiretroviral treatment history. The long-term effectiveness of raltegravir (RAL)-based salvage therapy was assessed through a longitudinal analysis of immunologic, virologic, and clinical status of the patients.

Results: Median age was 16.0 (15.0–18.0) years. At baseline, median HIV-1 RNA was 10,000 (4.0 log10 copies/mL) (interquartile range [IQR]: 4300–83,000), and median CD4+T-cell count was 329 (18.2% cells/μL) (IQR: 175–452). The backbone regimen included at least 1 fully active drug in 17/19 (89%) patients. Median follow-up with HAART including RAL was 80.1 weeks (IQR: 49.4–96.4): 16/19 (84%) exposed for >120 weeks and 6/19 (32%) >100 weeks. After RAL-based therapy, 4/19 (21%) patients achieved HIV-1 RNA <400 copies and 13/17 (68%) reached HIV-1 RNA <50 copies: 6 (32%) within the first month and 7 (37%) within the first 4 months. CD4+T-cell recovery (70% to 90% of the baseline values) was observed in 17/19 (89%) patients. No deaths, AIDS-defining illnesses, or symptoms of severe intolerance were recorded. Only 2 patients experienced mild-moderate short-term skin rash. Two (11%) patients had sustained and optimum adherence to HAART. No patients showed resistance mutations to RAL after follow-up.

Conclusions: We observed a sustained antiviral response and improved immunologic indices in multidrug-resistant pediatric patients, most of whom had received RAL as part of salvage regimens with at least 1 fully active drugs.

Author Information

From the *Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario “Gregorio Marañón,” Madrid, Spain; †Unidad de Infectología/Medicina Interna Pediátrica, Hospital Infantil Universitario “Virgen del Rocío,” Sevilla, Spain; ‡Unidad de Infectología e Inmunodeficiencias, Servicio de Pediatría, Hospital Regional Universitario “Carlos Haya,” Málaga, Spain; §Servicio Infecciosas Infantil, Hospital Universitario “La Paz,” Madrid, Spain; ¶Servicio de Infecciosas Pediátricas, Hospital Universitario “Doce de Octubre,” Madrid, Spain; ∥Servicio de Pediatría del Hospital Universitario San Juan, Alicante, Spain; **Unidad de Infectología Pediatrica, Hospital de Cruces, Bilbao, Spain; ††Servicio de Pediatría, Hospital Universitario de Getafe, Madrid, Spain; and ‡‡Immunovirology Laboratory of the Institute of Biomedicine of Seville (IBIS), Service of Infectious Diseases, Virgen del Rocío University Hospital, Seville, Spain.

Accepted for publication September 20, 2011.

V.B. and J.A.L-L. contributed equally to the manuscript.

Supported in part by grants from Red Temática de Investigación Cooperativa Sanitaria ISCIII (RED RIS RD06/0006/0035 and RD06/0006/0021), Fundación para la Investigación y Prevención del SIDA en España (FIPSE) (grants 24632/07 and 240800/09), Fondo de Investigación Sanitaria (INTRASALUD 2009; RD09/0076/00103; FIS07/0110), Fundación Caja Navarra, and the Paediatric European Network for Treatment of AIDS (PENTA). Verónica Briz is supported by the Fondo de Investigación Sanitaria through the Sara Borrell program (CD09/00433). Claudia Palladino is supported by The Spanish MICINN through the Juan de la Cierva program (JCI-2009-05650). The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Ma Άngeles Muñoz-Fernández, Laboratorio Inmuno-Biología Molecular, Hospital General Universitario, “Gregorio Marañón,” C/Doctor Esquerdo 46, 28007 Madrid, Spain. E-mail: mmunoz.hgugm@salud.madrid.org.

© 2012 by Lippincott Williams & Wilkins, Inc.