Diagnóstico precoz de la infección por VIH en niños y monitorización de la infección en población adulta infectada usando muestras de sangre seca

• Autores: Patricia Alvarez Muñoz
• Directores de la Tesis: Africa Holguín (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2017
• Idioma: español
• Tribunal Calificador de la Tesis: José María Almendral del Río (presid.), María José Mellado Peña (secret.), Pablo Rojo Conejo (voc.), Luis Prieto Tato (voc.), Rafael Delgado Vázquez (voc.)
• Programa de doctorado: Programa de Doctorado en Biociencias Moleculares por la Universidad Autónoma de Madrid
• Materias:
  • Ciencias económicas
    • Economía sectorial
      • Sanidad
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Dried blood specimens (DBS) represent an alternative sample type to liquid plasma for performing HIV-1 diagnostic techniques and monitoring antiretroviral therapy (ART) efficacy as they are easy to prepare, less biohazardous, do not require a cold chain, and can be shipped by standard mail at room temperature to a reference laboratory if required.

    In this Thesis, different studies focusing on the use of DBS as sample type to diagnose HIV-1 infection in infants, to quantify the HIV-1 viral load (VL), and to identify drug resistance mutations and HIV-1 variants are presented. A molecular epidemiological approach was used to analyze the results based on the different HIV-1 subtypes and recombinants included in the studies. Our results confirm that DBS can be used for HIV-1 VL quantification and for the detection of drug resistant mutations (DRM) in viruses, which can be useful for early therapeutic failure detection in treated subjects. However, VL in DBS can be overestimated in specimens with low VL in plasma, maybe due to a higher effect of proviral DNA in quantification. Considering that different VL assays provide different VL values for the same specimen, the use of the same VL technique for each patient during ART monitoring is recommended. Commercial VL assays using DBS were useful for early infant diagnosis, although discrepant results among the four assays analyzed in this Thesis were common. Further research is required to reduce false positive results that could result in wrong diagnosis and unneeded treatment. VL assays should also increase their sensitivity and specificity to avoid overestimated HIV-1 quantifications, which could be interpreted as virological failure events, or false negative diagnostic results due to genetic variability. As to the identification of DRM using DBS, the high rate of acquired drug resistance to retrotranscriptase inhibitors observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in countries as Equatorial Guinea to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.

    In summary, DBS collection is especially useful in settings with limited infrastructures or when low blood volume is available, as in infants. HIV-1 VL testing is useful for monitoring the efficacy of ART, detecting early therapeutic failure events, and performing an early infant diagnosis of the HIV infection. More studies including more HIV-1 variants are needed to define the performance of commercial virological assays when using DBS.