Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses

P Rojas Sánchez; M de Mulder; E Fernandez-Cooke; L Prieto; P Rojo; S Jiménez de Ory; M José Mellado; M Navarro; J Tomas Ramos; Á Holguín; Madrid Cohort of HIV-Infected Children and Adolescents Integrated in the Paediatric Branch of the Spanish National AIDS Network (CoRISPe)

doi:10.1016/j.cmi.2015.02.003

Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses

Clin Microbiol Infect. 2015 Jun;21(6):605.e1-9. doi: 10.1016/j.cmi.2015.02.003. Epub 2015 Feb 11.

Affiliations

¹ HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Universitario Ramón y Cajal-IRyCIS and CIBERESP, Spain.
² George Washington University, Washington, DC, USA.
³ Hospital Universitario Doce de Octubre, Spain.
⁴ Hospital Universitario de Getafe, Spain.
⁵ Hospital General Universitario Gregorio Marañón, Spain.
⁶ Hospital Universitario La Paz, Spain.
⁷ Servicio de Pediatría, Hospital Clinivo San Carlos, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
⁸ HIV-1 Molecular Epidemiology Laboratory, Microbiology and Parasitology Department, Hospital Universitario Ramón y Cajal-IRyCIS and CIBERESP, Spain. Electronic address: [email protected].

PMID: 25680310
DOI: 10.1016/j.cmi.2015.02.003

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.

Keywords: Adolescents; HIV-1; Madrid cohort; antiretroviral treatment; children; drug-resistant viruses; paediatric population; triple class failure; virologic failure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Anti-Retroviral Agents / pharmacology*
Anti-Retroviral Agents / therapeutic use*
Child
Child, Preschool
Cohort Studies
Drug Resistance, Multiple, Viral*
Female
Follow-Up Studies
Genotyping Techniques
HIV Infections / pathology*
HIV Infections / virology*
HIV-1 / drug effects*
HIV-1 / genetics
HIV-1 / isolation & purification*
Humans
Infant
Infant, Newborn
Male
Microbial Sensitivity Tests
Spain
Young Adult

Substances

Anti-Retroviral Agents