CD1d-restricted NKT cells express an invariant TCR and have been demonstrated to play an important regulatory role in a variety of immune responses. Invariant NKT cells down-regulate autoimmune responses by production of type 2 cytokines and can initiate antitumor and antimicrobial immune responses by production of type 1 cytokines. Although defects in the (invariant) Vα24+Vβ11+ NKT cell population have been observed in patients with cancer and autoimmune diseases, little is known regarding the protective role of Vα24+Vβ11+ NKT cells in human infectious disease. In a cross-sectional study in HIV-1-infected individuals, we found circulating numbers of Vα24+Vβ11+ NKT cells to be reduced, independent of CD4+ T cell counts, CD4:CD8 ratios, and viral load. Because a small minority of Vα24+Vβ11+ NKT cells of healthy donors expressed HIV-1 (co)receptors and the vast majority of Vα24+Vβ11+ NKT cells in HIV-1-infected individuals expressed the Fas receptor, the depletion was more likely due to Fas-mediated apoptosis than to preferential infection of Vα24+Vβ11+ NKT cells by HIV-1. A longitudinal cohort study, in which patients were analyzed before seroconversion and 1 and 5 years after seroconversion, demonstrated that a large proportion of the depletion occurred within the first year postseroconversion. In this longitudinal study no evidence was found to support an important role of Vα24+Vβ11+ NKT cells in determining the rate of progression during HIV-1 infection.
Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.
Despite a widely available PEP program in Amsterdam, the number of PEP requests remained low. Most people completed their PEP course; compliance with follow-up HIV testing was high.
No difference in adherence was found between the 2 regimens, even though fewer adverse effects were reported on regimen 2. ALT need not be routinely tested to monitor adverse effects. The 5 seroconversions were not likely caused by PEP failure, but rather by ongoing HIV exposures.
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