Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues

Abstract

Previous studies proposed a dynamic, steady-state relationship between HIV-mediated cell killing and T-cell proliferation, whereby highly active antiretroviral therapy (HAART) blocks viral replication and tips the balance toward CD4 + cell repopulation. In this report, we have analyzed blood and lymph node tissues obtained concurrently from HIV-infected patients before and after initiation of HAART. Activated T cells were significantly more frequent in lymph node tissue compared with blood at both time points. Ten weeks after HAART, the absolute number of lymphocytes per excised lymph node decreased, whereas the number of lymphocytes in the blood tended to increase. The relative proportions of lymphoid subsets were not significantly changed in tissue or blood by HAART. The expression levels of mRNA for several proinflammatory cytokines (IFN-γ, IL-1β, IL-6, and macrophage inflammatory protein-1α) were lower after HAART. After therapy, the expression of VCAM-1 and ICAM-1 -adhesion molecules known to mediate lymphocyte sequestration in lymphoid tissue -was also dramatically reduced. These data provide evidence suggesting that initial increases in blood CD4 + cell counts on HAART are due to redistribution and that this redistribution is mediated by resolution of the immune activation that had sequestered T cells within lymphoid tissues.

CD4 count and viral load time‐courses in patients treated with highly active antiretroviral therapy and association with the CDC staging system

“…This study demonstrates that the main increases in CD4 cell counts as a consequence of HAART occurred during the first 3 months of therapy, although the increase continued during the entire follow-up period, in concordance with the biphasic nature of immune reconstitution [14][15][16][17][18][19]. A study on a relatively low number of naïve and experienced patients followed up for 4 years found that the monthly increase in CD4 counts was 22.6 cells/mL in the initial 3 months, 8.1 cells/mL in the following 9 months, 6.8 cells/mL in the second year of treatment, 3.3 cells/mL in the third year and 1.7 cells/mL in the fourth year [2].…”

“…All forms were sent to a single institution for data to be transferred to a computer database. Patients were evaluated at baseline and at the 3rd, 6th and 12th months after starting NFV therapy [mean deviations 1 10.5 (95% confidence interval (CI) 9-12), [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and [1][2][3][4][5][6], respectively]. A large amount of sociodemographic, clinical and laboratory data, including CD4 cell count and viral load, was recorded for each patient.…”

Relationship between CD38 expression on peripheral blood T‐cells and monocytes, and response to antiretroviral therapy: A one‐year longitudinal study of a cohort of chronically infected ART‐naive HIV‐1+ patients

“…However, it should be noted that while a correlation was observed between viral load and CD38 expression among untreated HIV-1þ patients with >200 CD4þ PB T-cells, this was restricted to the expression of CD38 on CD4þ and CD8þ T-cells, suggesting that the increased CD38 expression on both T-cell subsets, but not the monocytes, is closely related to active viral replication in less immunocompromised HIV-1þ patients. The marked depletion of circulating CD4þ T-lymphocytes observed in HIV-1þ patients has been related, to a certain extent, to the increased migration of PB CD4þ T-cells to lymph nodes, where active replication is occurring (34)(35)(36); this could help to explain the absence of a correlation between CD38 expression on CD4þ T-lymphocytes and viral load in the <200CD4 HIV-1þ patient group, since in these immunocompromised patients most of their circulating activated CD4þ T-lymphocytes with high CD38 expression would be sequestered from PB into lymphoid tissues (27,37); it should be noted that HIV-1þ individuals from this group were asymptomatic patients who were not at the latest stages of the disease. In addition, CD8þ T-cell responses are impaired in HIV-1 infected patients at later stages of the disease (38), presumably because of the lack of appropriate helper signals.…”

“…In line with previous observations (15)(16)(17)(18), ART induced a progressive reduction of CD38 expression on CD8þ T-lymphocytes over time in both the <200CD4 and >200CD4 patient groups; by contrast, initiation of ART led to distinct kinetic changes in the pattern of CD38 expression on CD4þ T-cells for each of the two patient groups. Previous studies show that the increase of PB CD4þ T-cell counts observed early after starting ART could be attributed to a redistribution into PB of those CD4þ T-cells that had migrated to lymph nodes as a consequence of active viral replication, because of decreased viral load (27,37,50,51). In line with this, we observed an increased CD38 level on CD4þ T-lymphocytes early after initiation of therapy for the <200CD4 group in parallel with an early and rapid increase of CD4þ T-cell numbers at week þ2 of ART.…”

Immunomodulation in female B6C3F1mice following treatment with the HIV protease inhibitor saquinavir for 28 days by gavage

“…In addition, SQV treatment has been shown to affect cytokine production (Pacifici et al, 1997;Bucy et al, 1999;Gruber et al, 2001). The observed immunomodulatory effects of SQV in HIV patients following PI treatment might be due to either the direct effect of PIs on the immune system because these proteases were also involved in physiological processes concerning immune responses (Franzese et al, 2001) or their virus inhibition (indirect effects) because of the immunosuppressive effects of HIV.…”