RESUMEN
OBJECTIVES: With the advent of combined antiretroviral therapy (cART), perinatally HIV-infected children are surviving into adolescence and beyond. However, drug resistance mutations (DRMs) compromise viral control, affecting the long-term effectiveness of ART. The aims of this study were to detect and identify DRMs in a HIV-1 infected paediatric cohort. METHODS: Paired plasma and dried blood spots (DBSs) specimens were obtained from HIV-1 perinatally infected patients attending the Jacobi Medical Center, New York, USA. Clinical, virological and immunological data for these patients were analysed. HIV-1 pol sequences were generated from samples to identify DRMs according to the International AIDS Society (IAS) 2011 list. RESULTS: Forty-seven perinatally infected patients were selected, with a median age of 17.7 years, of whom 97.4% were carrying subtype B. They had a mean viral load of 3143 HIV-1 RNA copies/mL and a mean CD4 count of 486 cells/µL at the time of sampling. Nineteen patients (40.4%) had achieved undetectable viraemia (< 50 copies/mL) and 40.5% had a CD4 count of > 500 cells/µL. Most of the patients (97.9%) had received cART, including protease inhibitor (PI)-based regimens in 59.6% of cases. The DRM prevalence was 54.1, 27.6 and 27.0% for nucleoside reverse transcriptase inhibitors (NRTIs), PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Almost two-thirds (64.9%) of the patients harboured DRMs to at least one drug class and 5.4% were triple resistant. The mean nucleotide similarity between plasma and DBS sequences was 97.9%. Identical DRM profiles were present in 60% of plasma-DBS paired sequences. A total of 30 DRMs were detected in plasma and 26 in DBSs, with 23 present in both. CONCLUSIONS: Although more perinatally HIV-1-infected children are reaching adulthood as a result of advances in cART, our study cohort presented a high prevalence of resistant viruses, especially viruses resistant to NRTIs. DBS specimens can be used for DRM detection.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/genética , Inhibidores de Proteasas/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Adolescente , Preescolar , Estudios de Cohortes , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , VIH-1/clasificación , VIH-1/efectos de los fármacos , VIH-1/metabolismo , Humanos , Lactante , Recién Nacido , Masculino , Filogenia , Estados Unidos , Carga Viral , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/metabolismoRESUMEN
Understanding human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte responses is important for the development of vaccines and therapies. We describe a novel method for the rational selection of peptides that target stable regions of the HIV-1 genome, rich in epitopes specifically recognized by the study population. This method will be of particular use under resource/sample-limited conditions.
Asunto(s)
VIH-1/inmunología , Péptidos/economía , Péptidos/inmunología , Selección Genética , Linfocitos T Citotóxicos/inmunología , Secuencia de Aminoácidos , Epítopos/genética , Epítopos/inmunología , Genoma Viral , VIH-1/genética , Humanos , Datos de Secuencia Molecular , Péptidos/químicaRESUMEN
CD8 T cells are believed to play a key role in the immune control of human immunodeficiency virus-1 (HIV-1) infection in children as well as in adults. We have used an enhanced EliSpot (AmpliSpot) assay to quantitate CD8 T-cell responses directed to five human leucocyte antigen (HLA)-A2-presented HIV-1 epitopes derived from the key viral antigen Nef. Responses were assayed in one group of 21 children with vertically acquired HIV infection and one group of 19 adult subjects with chronic infection. The paediatric group displayed significantly weaker and more narrowly focused CD8 T-cell responses as compared with the adult subjects. Two epitopes stood out as the most frequently and strongly recognized, suggesting that they should be considered immunodominant in the CD8 T-cell response to HIV-1 Nef. Interestingly, the most frequently and strongly recognized epitope in both adults and children was previously identified in HLA-A2-transgenic mice, demonstrating the usefulness of such mice in finding natural viral epitopes. These findings indicate significant weakness in strength and breadth of the CD8 T-cell response to the target protein Nef in infected children and prompt renewed efforts into the immunology of vertically acquired HIV-1 infection.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Productos del Gen nef/inmunología , Infecciones por VIH/transmisión , Antígeno HLA-A2/inmunología , Transmisión Vertical de Enfermedad Infecciosa , Adulto , Animales , Niño , Epítopos de Linfocito T/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Humanos , Inmunidad Celular , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
Fc receptors are induced on T cells following activation via the TCR. T cells that express Fc receptors transiently have the ability to use two different cognate systems: the TCR and immunoglobulins bound to the Fc receptors. The studies discussed in this article are focused on the Fc alpha and Fc mu receptors that can be induced on certain subsets of murine T lymphocytes. The article emphasizes the role of the T cell receptor for antigen in the expression of Fc alpha and Fc mu receptors on murine T cells and reviews experimental observations that suggest significant molecular heterogeneity of these Fc receptors. The finding that regulation of expression of Fc alpha receptors and Fc mu receptors on T lymphocytes is linked to cellular activation via the CD3/TCR complex implies that these Fc receptors might mediate important functions in the biology and pathology of T cells.