RESUMEN
We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Eliminación de Gen , ADN Polimerasa Dirigida por ARN/genética , Zidovudina/uso terapéutico , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Farmacorresistencia Microbiana/genética , Femenino , Genotipo , Proteasa del VIH/genética , Humanos , Insuficiencia del TratamientoRESUMEN
Several studies had previously demonstrated the high sensitivity and specificity of JCV DNA detection in CSF by PCR. This paper reported the implementation of a simple PCR procedure to detect JCV in the CSF in a cohort of HIV-1 infected patients from Argentina. Years ago, the confirmatory diagnosis of this disease was made by in-situ hybridization or immunohistochemistry techniques on brain biopsies. The PCR procedure described here improves the diagnosis of PML because it is simple and noninvasive, and allows the differential diagnosis of PML from other neurological syndromes associated with AIDS. Many recent studies report a significant benefit of combined antiretroviral therapy on the survival of HIV patients without clear neurological improvements. A negative correlation has been described between the concentration of JCV in the CSF and survival time in HIV-1 infected patients, and the level of immune depression may influence JCV replication. This suggests that a single CSF JCV viral load determination during the course of PML disease progression may be of prognostic value for managing HIV patients.
Asunto(s)
ADN Viral/líquido cefalorraquídeo , Infecciones por VIH/complicaciones , Virus JC/genética , Leucoencefalopatía Multifocal Progresiva/virología , Reacción en Cadena de la Polimerasa , Adulto , Femenino , Humanos , Leucoencefalopatía Multifocal Progresiva/complicaciones , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Imagen por Resonancia Magnética , MasculinoRESUMEN
We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).
Asunto(s)
Sustitución de Aminoácidos , Codón/genética , Eliminación de Gen , Transcriptasa Inversa del VIH/genética , Adulto , Secuencia de Aminoácidos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Secuencia de Bases , Farmacorresistencia Microbiana/genética , Quimioterapia Combinada , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/enzimología , VIH-1/genética , Humanos , Datos de Secuencia Molecular , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
We evaluated phagolysosomal fusion in peripheral blood monocytes from 20 HIV-infected individuals and 40 normal controls, using a fluorescence assay with acridine orange as marker. The percentages of phagolysosomal fusion of monocytes from HIV-infected subjects, after 30 and 60 min of yeast ingestion, (mean +/- standard deviation) 57.2 +/- 17 and 63.2 +/- 18.6, respectively, when compared to normal controls (72.4 +/- 7.8 and 77 +/- 8.1), did not differ significantly. However, there was a direct linear association between the percentages of phagolysosomal fusion and CD4+ lymphocytes (P < 0.001) or CD4/CD8 T-cell ratio (P < 0.01). These results suggest that phagolysosomal dysfunction becomes evident at late stages of HIV infection and progresses as CD4+.T-lymphocyte count and CD4/CD8 T-cell ratio decrease. On the other hand, recombinant gp120 inhibited significantly normal phagolysosomal fusion at concentrations ranging between 1 and 1000 ng/ml. Taking together the results obtained, we can conclude that gp120 could be responsible for monocyte phagolysosomal dysfunction observed in HIV infected patients.
Asunto(s)
Infecciones por VIH/sangre , VIH-1 , Lisosomas/fisiología , Monocitos/fisiología , Fagosomas/fisiología , Adulto , Relación CD4-CD8 , Fusión Celular , Femenino , Proteína gp120 de Envoltorio del VIH/farmacología , Infecciones por VIH/patología , Humanos , Lisosomas/patología , Masculino , Persona de Mediana Edad , Fagocitosis , Fagosomas/patología , Proteínas Recombinantes/farmacologíaRESUMEN
We studied the functions of peripheral blood monocytes and polymorphonuclear cells in 15 apparently healthy homosexual men, eight homosexual or bisexual subjects with unexplained generalized lymphadenopathies (pre-AIDS), four homosexual men with acquired immunodeficiency syndrome (AIDS), and 15 heterosexual men. In comparison with normal controls, the homosexual groups studied presented a decreased monocyte candidacidal activity for Candida pseudotropicalis that gradually deteriorates as the clinical symptoms progress towards AIDS. The monocyte phagocytic function was retained. Although the phagocytic and candidacidal activities of the polymorphonuclear cells did not differ from those of the normal controls, the candidacidal activity in some of the cases studied was unusually enhanced, indicating that the cells were in an activated state. In addition, only two of nine sera tested from asymptomatic homosexual males were positive for antibodies to HTLV-III/LAV, while six out of eight pre-AIDS and both of the two AIDS patients tested had antibodies to AIDS-associated retrovirus. We suggest that in AIDS the phagocytic system is already involved, together with B and T lymphocyte abnormalities, during the early events of the syndrome, even without the detection of AIDS-associated retrovirus antibodies.