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Low CD4 T-cell counts despite low levels of circulating HIV : insights from the comparison of HIV-1 infected patients with a discordant response to antiretroviral therapy to patients with untreated advanced HIV-2 disease

Publication . Albuquerque, A. S.; Foxall, R. B.; Cortesão, C. S.; Soares, R. S.; Doroana, M.; Ribeiro, A.; Lucas, M.; Antunes, F.; Victorino, R. M.; Sousa, A. E.

A significant proportion of HIV-1+ patients with suppression of viremia under antiretroviral therapy fail to recover CD4(+) T-cell counts (ART-Discordants). Similarly, untreated HIV-2+ patients can also exhibit major CD4 depletion in spite of undetectable viremia. We characterize here the immunological disturbances associated with major CD4-lymphopenia in these two scenarios as compared to untreated viremic HIV-1+ patients with similar CD4-lymphopenia and HIV-1+ patients with successful immunological and virological responses under ART. Low CD4 counts were associated with major naive CD4 and CD8 depletion, irrespective of type of infection or ART-exposure. However, ART-Discordants exhibited lower levels of T-cell activation as compared to both untreated HIV-2 and HIV-1 cohorts, and a less marked increase in circulating IL-7 despite similar CD4 depletion. Nevertheless, ART-Discordants showed a preserved Bcl-2 expression, suggesting increased IL-7 consumption, which in conjunction with the relatively lower T-cell activation may contribute to their CD4 count stability and low rate of opportunistic infections.

2007Journal article

Restricted access

Efficient thymopoiesis contributes to the maintenance of peripheral CD4 T cells during chronic human immunodeficiency virus type 2 infection

Publication . Gautier, D.; Beq, S.; Cortesão, C. S.; Sousa, A. E.; Cheynier, R.

Human immunodeficiency virus type 2 (HIV-2) infection leads to a lifelong asymptomatic period in the majority of patients. Even in patients with progressive disease, a slow CD4 count decline characterizes the chronic phase of HIV-2 infection, suggesting that peripheral T-cell homeostasis is controlled better following HIV-2 infection than following HIV-1 infection. Herein we showed that, in contrast to HIV-1-infected patients, HIV-2-infected patients demonstrate enhanced thymic function compared to age-matched healthy individuals. The correlation between higher thymic production and lower CD4 T-cell loss in these patients suggests that efficient thymopoiesis is implicated in the long-lasting maintenance of CD4 T-cell counts in HIV-2 disease.

2007Journal article

Open access