Immune Dysregulation and T-Cell Activation Antigens in HIV Infection - Cellular Aspects of HIV Infection - page 44

would allow initiation of alternative, and hopefully more successful, drug regi-
mens. This necessity has stimulated in-depth analyses ®nalized at the de®nition
of possible prognostic markers capable of predicting which patients will more
likely be therapeutic failures. For example, consistent with their negative prog-
nostic value, an elevated percentage of CD8 CD38 T lymphocytes might
predict unresponsiveness to HAART. The biologic basis for negative prognos-
tic value of CD8 CD38 T cells is unknown; di¨erent hypotheses have been
put forward to explain these puzzling observations. To summarize, augmented
percentage and/or expression of CD8/CD38 could be a poor prognostic factor
in HIV infection because 1) CD8 CD38 T cells mediate cytotoxicity directed
toward autologous HIV-infected and uninfected CD4 T cells; 2) CD8 CD38
T cells are immature T cells, thus indicating the abnormality of the immune
system and possible alterations in hemopoiesis; 3) CD8 CD38 T cells might
be poor producers of antiviral factors; and 4) CD8 CD38 T cells might be the
immune correlate of response to high loads of virus.
Because augmented percentages of CD8 CD38 T cells could be an early
predictor of treatment failure, particular attention should be given to those
individuals in whom an abnormal augmentation of this subset is detected.
Finally, it must be underlined that the e¨ects of HAART in reconstituting the
functionality of the immune response (e.g., antigen-stimulated proliferation and
cytokine production) is still less than optimal (Clerici et al., 2000; Martinon et
al., 1999). This observation strongly supports the concept that immune modu-
lation has to be considered an essential component of the therapeutic approach
to HIV infection.
Acknowledgments. Supported by grants from Istituto Superiore di Sanit II
Programma Nazionale di Ricerca sull' AIDS 1998.
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