Interferon-alpha generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection.

OBJECTIVES

To quantify the effect of HIV infection and HIV-suppressive therapy on interferon-alpha (IFN-alpha) production by human blood mononuclear cells; to compare, in parallel, effects on CD4+ T-cell numbers; and to ascertain the relationship of these interferon and CD4 parameters to resistance to opportunistic infections.

DESIGN

Serial studies of 294 unselected patients with HIV infection during therapy, with outcomes analysis.

METHODS

Determination of IFN generation by blood mononuclear cells via bioassay, and T-lymphocyte subset analysis via flow cytometry; serial studies of individual patients; linear regression and chi2 contingency table analysis.

RESULTS

HIV burden is inversely related to interferon-alpha generation, much as it is to CD4+ T-cell counts. Both of these recover during HIV-suppressive therapy. Reconstitution of IFN-alpha generation to levels commensurate with protection against opportunistic infection occurs prior to similar restoration of CD4 counts. In the outcomes analyses, such immune reconstitution was associated with protection from recurrent or new opportunistic infection. Conversely, viral suppression without such immunologic recovery was not protective against opportunistic infection.

CONCLUSIONS

Rapidly responding IFN-alpha generating cells appear to participate in resistance to opportunistic intracellular infection. Recovery of IFN-alpha generation may be an early marker of immune reconstitution in AIDS.