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

cART 开始时 CD4 计数对 HIV-1 感染患者病毒和免疫库构成的主要影响

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作者:Anne-Emmanuelle Depincé-Berger, Delphine Vergnon-Miszczycha, Alexandre Girard, Anne Frésard, Elisabeth Botelho-Nevers, Claude Lambert, Emilie Del Tedesco, Christian Genin, Bruno Pozzetto, Frédéric Lucht, Xavier Roblin, Thomas Bourlet, Stéphane Paul

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.

Conclusions

An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution.

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.

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