Impact of lopinavir-ritonavir exposure in HIV-1 infected children and adolescents in Madrid, Spain during 2000-2014

• Published in: PloS one 2017-03, Vol.12 (3), p.e0173168-e0173168
• Main Authors: Rojas Sánchez, Patricia, Prieto, Luis, Jiménez De Ory, Santiago, Fernández Cooke, Elisa, Navarro, Maria Luisa, Ramos, José Tomas, Holguín, África
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adhesion; Adolescent; Adolescents; Adults; Age; AIDS; Amplification; Antimicrobial agents; Antiretroviral agents; Antiretroviral drugs; Antiviral agents; Antiviral drugs; Biology and Life Sciences; Care and treatment; CD4 antigen; CD4 Lymphocyte Count; CD4-CD8 Ratio; CD8 antigen; Child; Child, Preschool; Children; Classification; Clinical trials; Cohort Studies; Combination drug therapy; Committees; Diagnosis; Dosage and administration; Drug Combinations; Drug resistance; Drug Resistance, Viral - genetics; Drugs; Enzyme-linked immunosorbent assay; Epidemiology; Ethics; Exposure; Female; Grain; Health aspects; Highly active antiretroviral therapy; HIV; HIV infections; 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; Human immunodeficiency virus; Humans; Immunology; Incidence; Infant; Infant, Newborn; Infants; Infectious diseases; Inhibitors; Lamivudine; Lopinavir; Lopinavir - therapeutic use; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Microbiology; Morbidity; Mutation; Parents; Pediatrics; People and Places; Population studies; Predictions; Prognosis; Prophylaxis; Protease inhibitors; Proteinase; Proteinase inhibitors; Protocol (computers); Ribonucleic acid; Ritonavir; Ritonavir - therapeutic use; RNA; Sexually transmitted diseases; Side effects; Spain - epidemiology; STD; Teenagers; Therapy; Treatment Outcome; Viral Load - drug effects; Viremia - virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0173168

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. 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. 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. 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.