title: Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.
abstract: Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.
authors: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Universitario Ramón y Cajal-IRyCIS and CIBERESP, Spain.
authors: P
authors: P
authors: Rojas Sánchez
authors: George Washington University, Washington, DC, USA.
authors: M
authors: M
authors: de Mulder
authors: Hospital Universitario Doce de Octubre, Spain.
authors: E
authors: E
authors: Fernandez-Cooke
authors: Hospital Universitario de Getafe, Spain.
authors: L
authors: L
authors: Prieto
authors: Hospital Universitario Doce de Octubre, Spain.
authors: P
authors: P
authors: Rojo
authors: Hospital General Universitario Gregorio Marañón, Spain.
authors: S
authors: S
authors: Jiménez de Ory
authors: Hospital Universitario La Paz, Spain.
authors: M
authors: M
authors: José Mellado
authors: Hospital General Universitario Gregorio Marañón, Spain.
authors: M
authors: M
authors: Navarro
authors: Servicio de Pediatría, Hospital Clinivo San Carlos, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
authors: J
authors: J
authors: Tomas Ramos
authors: HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Universitario Ramón y Cajal-IRyCIS and CIBERESP, Spain. Electronic address: africa.holguin@salud.madrid.org.
authors: Á
authors: Á
authors: Holguín
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D015658:HIV Infections / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D013030:Spain; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents
keywords: Adolescents; HIV-1; Madrid cohort; antiretroviral treatment; children; drug-resistant viruses; paediatric population; triple class failure; virologic failure