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Trends in Drug Resistance Prevalence in HIV-1infected Children in Madrid: 1993 to 2010 Analysis

de Mulder, Miguel MSc*; Yebra, Gonzalo PhD*; Navas, Adriana MD; Martin, Leticia Tech*; de Jose, Maria Isabel MD; Navarro, Maria Luisa MD§; de Ory, Santiago Jimenez MSc; Gonzalez-Granado, Ignacio MD; Mellado, Maria Jose MD**; Ramos, Jose Tomas MD††; Holguin, Africa PhD*

Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0b013e3182678c7c
HIV Reports
Abstract

Background: Drug resistance mutations compromise antiretroviral treatment (ART) effectiveness in HIV-1–infected children. Trends in drug resistance prevalence have not been previously evaluated in HIV-infected children in Spain.

Methods: HIV-1 variants, drug resistance prevalence dynamics and drug susceptibility were analyzed from 1993 to 2010 in HIV-infected children with available pol sequence, sample or drug resistance profile. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations in pretreated and naive patients were identified according to International AIDS Society-2010 and the World Health Organization list, respectively.

Results: In 232 patients, genotypic resistance profiles (n = 11) or pol sequences (n = 128) were recovered or newly generated from infected samples (n = 93). Patients were mainly in care at pediatric units (63%), were mostly Europeans (84%), with moderate AIDS symptoms (65%), on ART (91%) and infected by HIV-1 subtype B (89%). Transmitted major drug resistance mutations were selected in 6 (13.6%) of the 44 ART-naive children: 4.8%, 9.3% and 11.6%, for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Overall resistance prevalence was higher (71.8%) among ART-exposed children: 39.9%, 66.5% and 35.3% for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Resistance prevalence among ART-exposed children was higher in 2009 to 2010 relative to 1993 to1999 for nonnucleoside reverse transcriptase inhibitors (42% versus 6%; P = 0.006), protease inhibitors (39% versus 13%; P = 0.004) and nucleoside reverse transcriptase inhibitors (63% versus 44%; P = NS). Susceptibility to each drug in resistant viruses was predicted. The rate of non-B infections increased in the last years, mainly caused by recombinant viruses.

Conclusions: The increasing resistance prevalence among the HIV-infected pediatric population in Spain highlights the importance of specific drug resistance and drug susceptibility surveillance in long-term pretreated children to optimize treatment regimens.

Author Information

From the *HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Unit, Hospital Universitario Ramón y Cajal-IRyCIS and CIBER-ESP; Pediatrics Unit, Hospital Universitario Infanta Leonor; Pediatrics Unit, Hospital Universitario de La Paz; §Pediatrics Unit, Hospital General Universitario Gregorio Marañón, Molecular Immunobiology Laboratory, Hospital General Universitario Gregorio Marañon, Pediatrics Unit, Hospital Universitario Doce de Octubre; **Pediatrics Unit, Hospital Carlos III; and ††Pediatrics Unit, Hospital Universitario de Getafe, Madrid, Spain.

This work was supported in part by grants from Fondo de Investigaciones Sanitarias (FIS), from Ministerio de Ciencia e Innovación (grant PI09/00284 and grant PI07/0236) and from Fundación para la Investigación y Prevención del SIDA en España (FIPSE, grant 360829/09). MM is supported by PI07/0236 and PI07/0236. GY is supported by Consejería de Educación de la Comunidad de Madrid and Fondo Social Europeo (FSE). AH is supported by Agencia Laín Entralgo. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Africa Holguín, PhD, HIV-1 Molecular Epidemiology Laboratory, Department of Microbiology, Hospital Universitario Ramón y Cajal, Ctra. Colmenar Viejo km. 9,100, 28034 Madrid, Spain. E-mail: aholguin.hciii@salud.madrid.org.

© 2012 Lippincott Williams & Wilkins, Inc.