Immune Restoration after Treatment of HIV-1 Infection with Highly Active Antiretroviral Therapy (HAART)

The availability of combination antiretroviral therapy (HAART) has been associated with dramatic decreases in HIV-related morbidity and mortality. These clinical benefits are probably mediated by a decrease in HIV-1 replication and an increase in the number and function of peripheral blood CD4+ lymphocytes. Despite many years of maintaining plasma HIV-1 RNA levels below the limits of detection, many patients do not achieve normal CD4+ lymphocyte counts. A larger proportion of patients who delay HAART for longer have incomplete numerical CD4+ restoration compared to patients who start therapy earlier. Even in patients who normalize their CD4+ lymphocytes insert counts, immune function remains impaired among those who delay HAART for longer periods. Whether subclinical immune deficiency will be associated over longer periods of follow-up with adverse clinical outcomes such as an increased number of infections and malignancies remains to be determined. If prolonged subclinical immunodeficiency is associated with adverse outcomes, the use of immunebased therapies may benefits patients while helping us ascertain the residual deficits responsible for incomplete immune restoration.