Objective: To determine the extent to which HIV-infected patients, including those with advanced immunodeficiency, can reverse peripheral CD4 T-cell depletion while maintaining long-term viral suppression on highly active antiretroviral therapy.
Design: Cohort study.
Participants: Four-hundred and twenty-three HIV-infected patients who initiated HAART prior to 1998 and achieved a viral load ≤ 1000 copies/ml by 48 weeks were evaluated for up to 4 years or until plasma HIV RNA levels increased to > 1000 copies/ml.
Main outcome measure: CD4 count changes.
Results: Among patients who maintained plasma HIV RNA levels ≤ 1000 copies/ml, CD4 counts continued to increase through year 4 of HAART. In the last year examined, from year 3 to 4 of HAART, mean CD4 count gains were +89 × 106, +86 × 106, +95 × 106, and +88 × 106/l in patients with pre-therapy CD4 counts of < 50 × 106, 50 × 106-199 × 106, 200 × 106-349 × 106, and ≥ 350 × 106/l, respectively (all gains were significantly greater than zero; P < 0.05). Among those with a pre-therapy CD4 count of < 50 × 106/l, 88% achieved a CD4 cell count of ≥ 200 × 106/l and 59% achieved a count of ≥ 350 × 106/l by year 4. Factors associated with increased CD4 cell count gains from month 3 to year 4 included lower pre-therapy CD4 cell count, younger age, female sex, and infrequent low-level viremia (versus sustained undetectable viremia).
Conclusions: Most patients who achieve and maintain viral suppression on HAART continue to experience CD4 T-cell gains through 4 years of therapy. The immune system's capacity for CD4 T lymphocyte restoration is not limited by low pre-therapy CD4 counts.