ABSTRACT
OBJECTIVES: The C allele of the single nucleotide polymorphism rs12979860, located near the interleukin-28B (IL-28B) gene, has a strong impact on hepatitis C virus (HCV) treatment response, as well as on spontaneous viral clearance. In patients with chronic hepatitis C (CHC), genotype CC carriers harbour HCV genotype 3 more commonly than those with non-CC genotypes. The aim of this study was to compare the HCV genotype distributions, according to IL-28B genotype, in HIV-infected patients with CHC and those with acute hepatitis C (AHC). METHODS: The rs12979860 genotype was determined by polymerase chain reaction (PCR) in two subpopulations of HIV-infected patients. The first consisted of 80 German patients with AHC. The second consisted of 476 patients with CHC, belonging to one German and two Spanish cohorts. RESULTS: In the AHC group, 31 (81.6%) rs12979860 CC carriers were infected with HCV genotype 1 or 4 vs. 32 (76.2%) among non-CC carriers (P=0.948). In patients with CHC, among those with the CC genotype, 119 (54.6%) were infected with HCV genotype 1 or 4 and 99 (45.4%) with genotype 2 or 3, whereas in the subset with non-CC genotypes, 200 (77.5%) harboured HCV genotype 1 or 4 and 58 (22.5%) genotype 2 or 3 (P<0.001). CONCLUSIONS: Among HIV-infected patients with CHC, those bearing the IL-28B genotype CC were more commonly infected with genotype 3 than subjects with non-CC genotypes, whereas in HIV-infected subjects with AHC this finding was not obtained. These results strongly suggest that the protective effect of the CC genotype against evolution to CHC is mainly exerted in patients infected with HCV genotype 1 or 4.
Subject(s)
Hepacivirus/genetics , Hepatitis C, Chronic/virology , Hepatitis C/virology , Interleukins/genetics , Adult , Coinfection , Female , Genotype , HIV Infections/complications , HIV Infections/virology , Hepacivirus/classification , Hepatitis C/complications , Hepatitis C/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/genetics , Humans , Interferons , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
Introducción. Uno de los elementos que mayor peso tiene en la decisión del momento de inicio de terapia antirretroviral es el riesgo de progresión a sida. El objetivo del presente trabajo fue caracterizar el perfil inmunofenotípico basal de pacientes que progresan a sida. Material y métodos. Estudio transversal de la distribución de subpoblaciones funcionales de linfocitos T CD4+ y CD8+ en 85 pacientes adictos a drogas por vía parenteral (ADVP) con infección por el virus de la inmunodeficiencia humana (VIH). Se analizaron los valores observados a la entrada de los pacientes en un estudio prospectivo. Los valores de los pacientes progresores y no progresores se compararon con grupos control sin infección VIH. Las subpoblaciones linfocitarias se estudiaron mediante citometría de flujo incluyendo los marcadores CD3, CD4, CD7, CD8, CD45RO, CD38, HLA-DR y CD25. Resultados. El perfil inmunofenotípico que precede a la progresión a sida se caracteriza principalmente por un aumento de células de memoria (CD45RO+) CD4+ y CD8+ activadas, aumento de células CD4+ y CD8+ totales activadas y por un incremento de células T CD4+ que han perdido la expresión de marcadores como el receptor de la IL-2 (CD25) o del marcador de diferenciación CD7 (CD7). Los pacientes que no reunían en el estudio basal criterios de laboratorio para iniciar tratamiento antirretroviral (> 350 células CD4+ y < 30.000 copias ARN-VIH-1/ml) mostraron también más activación sobre células CD4+ y CD8+ (CD4+CD38+DR+, CD8+CD38+). Discusión. El que la activación inmunológica pueda contribuir al deterioro clínico e inmunológico de los pacientes es un elemento adicional que podría tenerse en cuenta a la hora de decidir cuándo iniciar terapia antirretroviral
Introduction. One key piece of information required when deciding whether to initiate antiretroviral therapy is the risk of AIDS. The aim of this study was to better characterize the baseline immunophenotypic profile of patients with progression to AIDS. Material and methods. A cross-sectional analysis of the distribution of functional subpopulations of CD4+ and CD8+ T-lymphocytes in 85 intravenous drug addicts with HIV infection. The values observed on patient enrolment in a prospective study were analyzed. Those patients who progressed and did not progress were compared to the HIV-negative controls. Lymphocyte subpopulations were studied by flow cytometry, including the markers: CD3, CD4, CD7, CD8, CD45RO, CD38, HLA-DR and CD25. Results. The immunophenotypic profile that precedes progression to AIDS was mainly characterized by an increase in memory (CD45RO) activated cells and total activated CD4+ and CD8+ cells, and by an increase of T CD4+ cells that have loss expression of markers as receptor or the differentiation marker CD7 (CD7). Patients not meeting laboratory criteria to initiate antiretroviral therapy (> 350 CD4+ T-cells and < 30,000 HIV-ARN-copies/ml) also showed increased levels of CD4+ and CD8+ activation subsets (CD4+CD38+DR+, CD8+CD38+). Discussion. The fact that immunological activation may contribute to immunological and clinical deterioration of HIV-positive patients might be an additional factor which should be taken into account when deciding whether to initiate antiretroviral therapy
