Impact of Lopinavir-Ritonavir Exposure in HIV-1 Infected Children and Adolescents in Madrid, Spain During 2000-2014

PLoS One. 2017 Mar 28;12(3):e0173168. doi: 10.1371/journal.pone.0173168. eCollection 2017.


Background: The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain.

Methodology: Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure. Drug resistance mutations (DRM) were identified in viruses from samples collected until 2011. We predicted drug susceptibility to 19 antiretrovirals among those carrying DRM using the Stanford's HIVdb Algorithm.

Results: A total of 199 (37.3%) of the 534 patients from the cohort were exposed to LPV/r during 2000-2014 in first (group 1), second (group 2) or more line-therapies (group 3). Patients were mainly Spaniards (81.9%), perinatally infected (96.5%) with subtype-B (65.3%) and HIV-diagnosed before year 2000 (67.8%). The mean age at first LPV/r exposure was 9.7 years. After protease-inhibitor exposure, viral suppression was higher in groups 1 and 2 than in group 3. Viral suppression occurred in 87.5%, 68.6% and 64.8% patients from groups 1, 2 and 3, respectively. Among the 64 patients with available resistance data during LPV/r treatment, 27(42.3%) carried DRM to protease-inhibitor, 28 (58.3%) to reverse-transcriptase-inhibitors and 21 (43.7%) to non-reverse-transcriptase-inhibitors. Darunavir/ritonavir, atazanavir-ritonavir and tipranavir/ritonavir presented the highest susceptibility and nelfinavir the lowest.

Conclusions: A better lymphocyte recovering occurred when protease-inhibitor was taken as part of a first-line regimen and a higher number of patients reached viral suppression. The least compromised antiretrovirals for rescue antiretroviral regimens, according to DRM in the LPV/r-exposed-paediatric cohort, were mainly the new protease inhibitors.

MeSH terms

  • Adolescent
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Combinations
  • Drug Resistance, Viral / genetics
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Infant
  • Infant, Newborn
  • Lopinavir / therapeutic use*
  • Male
  • Mutation
  • Ritonavir / therapeutic use*
  • Spain / epidemiology
  • Treatment Outcome
  • Viral Load / drug effects
  • Viremia / virology


  • Drug Combinations
  • HIV Protease Inhibitors
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Ritonavir

Grant support

This study was supported by Plan Nacional de I+D+I 2008-2011, Instituto de Salud Carlos III (ISCIII), FIS PI12/00240 and cofinanced by the European Development Regional Fund “A way to achieve Europe” (ERDF). This study is included in the ‘Subprograma de Inmigración y Salud from CIBERESP (Spain). We want to particularly acknowledge the patients in this study for their participation and the Pediatric HIV BioBank integrated in the Spanish AIDS Research Network for providing two clinical samples used in this work. The Pediatric HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant n° RD06/0006/0035) and Fundación para la investigación y prevención del SIDA en España (FIPSE). CoRISPe cohort is funded by RD12/0017/0035 and RD12/0017/0037 Project, supported by Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdirección General de Evaluación and European Development Regional Fund “A way to achieve Europe” (ERDF). We thank CoRISPE and the professionals responsible for the routine resistance testing in the participant hospitals for providing epidemiological-clinical data and pol sequences of enrolled patients when available.