CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression

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, 1350 cells/ mL, 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/mu L, with 92% of patients having an increase in CD4(+) cell count. By 6 years, the median CD4(+) cell count was 493 cells/mu L among patients with baseline CD4(+) cell counts <= 200 cells/mu L, 508 cells/ mL among those with baseline CD4(+) cell counts of 201 - 350 cells/mu L, and 829 cells/mu L among those with baseline CD4(+) cell counts 1350 cells/ mL. 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 1350 cells/ mL 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.