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.
From the aPositive Health Program, San Francisco General Hospital, University of California, the bDivision of General Internal Medicine, Veterans Affairs Medical Center, San Francisco, California, the cCenter for AIDS Research, Case Western Reserve University, University Hospitals, Cleveland, Ohio, the dCommunity Consortium, San Francisco, California, the eDepartments of Medicine and Health Services, University of Washington, Seattle, Washington, the fCenter for AIDS Prevention Studies, University of California, and the gDepartment of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
Requests for reprints to: J. N. Martin, Center for AIDS Prevention Studies, Prevention Sciences Group, 74 New Montgomery Street, Suite 200, San Francisco, CA 94105, USA.
Received: 21 November 2002; revised: 11 March 2003; accepted: 18 March 2003.