Background:  Sustained suppression of HIV-1 RNA by HAART results in immunologic improvement, even among those with low pre-therapy CD4 levels. However, it is not as clear whether the CD4 will improve to normal levels, or whether it reaches a plateau over time. We wished to characterize the increase in CD4 level in patients in clinical practice who maintained sustained virologic suppression for as long as 5 years. 

Methods:  All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients in primary HIV care in Baltimore, Maryland, who were followed for at least 1 year on a HAART regimen, and who had a sustained HIV RNA suppression to <400 copies/mL for the duration of therapy. We analyzed the annual change in CD4 from for as long as 5 years from the start of HAART. The analysis was stratified by baseline CD4 as <200, 201 to 350, >350 cells/mL. We compared the overall and annual incremental change (slope) in CD4. 

Results:  We followed 262 patients for a mean of 1225 days (range 366 to 3300). Median age = 39 years, with 68% male, 66% black, 30% injecting drug user (IDU) risk, and mean baseline CD4 of 234 (Q1 57, Q4 372).  The mean change from baseline to last CD4 was +258 cells, with 91% of patients having a CD4 increase. By 5 years, mean CD4 was 423 in those with baseline CD4 <200, 501 for baseline CD4 201 to 350, and 681 for baseline CD4 >350 (Figure 1). For all CD4 strata, the largest increase in CD4 slope was in year 1. For baseline CD4 <200 (Figure 2), significant increases in the CD4 slope were seen each year (all p <0.05). Significant increases were also seen through year 3 for baseline CD4 201 to 350 (p <0.05), but no differences in slope in years 4 to 5. There were no significant annual increase in the CD4 slope beyond year 1 in those with baseline CD4 >350. 

Conclusions:  Only patients with baseline CD4 >350 returned to near normal CD4 levels. Significant increases in CD4 are seen in all baseline CD4 strata during the first year. Thereafter, the CD4 continues to increase annually for 5 years only if the baseline CD4 <200. The incremental increase is not as great at higher baseline CD4 levels suggesting a plateau effect.