Background.  Sustained suppression of the human immunodeficiency virus (HIV) type 1 RNA load with the use of highly active antiretroviral therapy (HAART) results in immunologic improvement, but it is not clear whether the CD4⁺ cell count increases to normal levels or whether it reaches a less-than-normal plateau. We characterized the increase in the CD4⁺ cell count in patients in clinical practice who maintained sustained viral suppression for up to 6 years.

Methods.  All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients receiving primary HIV care in Baltimore, Maryland, who were observed for >1 year while receiving HAART and who had sustained suppression of the HIV RNA load at <400 copies/mL. We analyzed annual change in the CD4⁺ cell count for up to 6 years after the start of HAART, stratified by baseline CD4⁺ cell counts of 200, 201–350, >350 cells/μL, and we assessed the development of clinical events (death and new acquired immunodeficiency syndrome–defining illness) by Kaplan-Meier analysis.

Results.  A total of 655 patients were observed for a median of 46 months (range, 13–72 months). The median change from baseline to most recent CD4⁺ cell count was +274 cells/μL, with 92% of patients having an increase in CD4⁺ cell count. By 6 years, the median CD4⁺ cell count was 493 cells/μL among patients with baseline CD4⁺ cell counts 200 cells/μL, 508 cells/μL among those with baseline CD4⁺ cell counts of 201–350 cells/μL, and 829 cells/μL among those with baseline CD4⁺ cell counts >350 cells/μL. In addition to baseline CD4⁺ cell count, injection drug use and older age were associated with a lesser CD4⁺ cell count response, and duration of therapy was associated with a greater CD4⁺ cell count response.

Conclusion.  Only patients with baseline CD4⁺ cell counts >350 cells/μL returned to nearly normal CD4⁺ cell counts after 6 years of follow-up. Significant increases were observed in all CD4⁺ cell count strata during the first year, but there was a lower plateau CD4⁺ cell count at lower baseline CD4⁺ cell strata. These data suggest that waiting to start HAART at lower CD4⁺ cell counts will result in the CD4⁺ cell count not returning to normal levels.