Cargando…

Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients

BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in...

Descripción completa

Detalles Bibliográficos
Autores principales: Depincé-Berger, Anne-Emmanuelle, Vergnon-Miszczycha, Delphine, Girard, Alexandre, Frésard, Anne, Botelho-Nevers, Elisabeth, Lambert, Claude, Del Tedesco, Emilie, Genin, Christian, Pozzetto, Bruno, Lucht, Frédéric, Roblin, Xavier, Bourlet, Thomas, Paul, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929778/
https://www.ncbi.nlm.nih.gov/pubmed/27363286
http://dx.doi.org/10.1186/s12977-016-0278-5
Descripción
Sumario:BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. RESULTS: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) (“high-level CD4 group”) and 15 < 350/mm(3) (“low-level CD4 group”) in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the “low-level CD4 group” of patients. The alteration in β7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the “high-level CD4 group” of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. CONCLUSIONS: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0278-5) contains supplementary material, which is available to authorized users.