Chronic immune activation reduces CD4+T cell susceptibility to IL-7 in HIV-infected patients that poorly respond to antiretroviral therapy

Approximately 30 % of HIV-infected patients with viral load being suppressed during the course of antiretroviral therapy do not recover their peripheral CD4+T-lymphocyte counts. The reason for this phenomenon, named immunological non-response to treatment, remains unknown. In HIV-positive subjects receiving treatment, interleukin 7 plays a key role in increasing the number and supporting the viability of CD4⁺T-lymphocytes. We hypothesized that chronic immune activation, which develops in response to immunological failure during the therapy course, may reduce the susceptibility of CD4⁺T-cells to interleukin 7 in HIV-positive subjects. We examined 38 HIV-infected immunological non-responders to therapy; 42 HIVpositive patients with a standard response to treatment; 19 uninfected volunteers. The content of CD4⁺, CD4⁺CD127⁺ and activated HLA-DR⁺CD38⁺T-lymphocytes was determined in the peripheral blood of the examined individuals; the concentration of interleukin 7 was established. As a result, it was shown that interleukin 7 concentrations in the blood plasma of HIV positive immunological non-responders to treatment does not differ from the corresponding values of patients who gave a standard response to antiretroviral therapy. At the same time, immunological non-responders to treatment compared with subjects of both control groups were characterized by a deficiency of absolute and relative CD4⁺CD127⁺T-cell counts capable of responding to interleukin 7. Moreover, the interleukin 7 receptor expression level was reduced on CD4⁺T-lymphocytes of immunological non-responders. The higher was the frequency of activated CD4⁺T-lymphocytes; the lower was the CD127⁺ expression density. It should be noted that after excluding the data obtained from patients coinfected with HIV and hepatitis C virus, which are known to have significantly higher levels of chronic immune activation and systemic inflammation, we found no differences in CD127 expression between HIVpositive patients with distinct effectiveness of the immunological response to treatment. Thus, in the present study, we showed that in HIV-infection, poor immunologic response to antiretroviral therapy is associated with a decrease in the CD4⁺CD127⁺T-cell counts. Moreover, an increase in the level of chronic immune activation is associated with a decrease in CD127 expression density on CD4⁺T-lymphocytes.