Recent dramatic decreases in acquired immunodeficiency syndrome–related
mortality are largely due to the introduction of highly active antiretroviral
therapy (HAART). Although immune restoration due to suppression of human immunodeficiency
virus (HIV) replication is a critical determinant of these trends, the magnitude
of immune restoration seen after treatment with HAART varies substantially
among treated persons and is generally incomplete. Nonetheless, even partial
immune restoration is sufficient to provide protection from most major opportunistic
infections; these risks can be largely predicted by the number of circulating
CD4 cells. Limited data suggest that treatment earlier during the course of
HIV infection may result in greater preservation of immune function, though
this has not been studied in great detail. Preliminary studies performed among
persons with multidrug-resistant virus whose treatment regimens are failing
suggest that there is likely a benefit to continuation of therapy that may
be related to diminished pathogenicity of drug-resistant virus. As deaths
related to opportunistic infections diminish, the spectrum of causes of mortality
in HIV infection is changing. Except for Kaposi sarcoma, there is insufficient
information to conclude that the risks of non-Hodgkin lymphoma and other malignancies
are diminishing among persons with HIV infection. How much immune restoration
will be enough to ensure long-term survival in persons with HIV infection
remains an open question.
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