Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy ( HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4(+) T cells have decreased below a certain threshold. This study addressed the long-term response of CD4(+) T-cell counts in patients on HAART and analyzed the influence of baseline CD4(+) T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4(+) T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4(+) T cells: <200 cells/mm(3), 200-349 cells/mm(3), 350-499 cells/mm(3), and greater than or equal to500 cells/mm(3). The main outcome measures were proportion of patients with CD4(+) T cells <200/mm(3) and >500/mm(3) at last determination and rate of CD4(+) T-cell recovery. Patients were followed-tip for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4(+) T cells increased in the whole cohort from a median of 214 cells/mm(3) (IQR, 90-355) to 499 cells/mm(3) (IQR, 312-733) (P < 0.001). Compared with the group with a baseline CD4(+) T-cell count of greater than or equal to500/mm(3), the relative risk of having a last determination of CD4(+) T-cell counts >200 cells/mm(3) was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4(+) T cells <200 cells/mm(3), 200-349 cells/mm(3), and 350-499 cells/mm(3), respectively. The relative risk of having a last determination of CD4(+) T-cell counts >500 cells/mm(3) was 0.32 (95% CI, 0.27-0.39, P < 0.001), 0.69 (95% CI, 0.60-0.79, P < 0.001), and 0.94 (95% CI, 0.83-1.06, P = 0.38) for baseline CD4(+) T-cell counts <200 cells/mm(3), 200-349 cells/mm(3), and 350-499 cells/mm(3), respectively, compared with a baseline CD4(+) T-cell count of greater than or equal to500 cells/mm(3). The increase in CD4(+) T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4(+) T-cell count. However, patients who start therapy with a CD4(+) T-cell count <200 cells/mm(3) have poorer immunologic outcome as measured by the proportion of patients with CD4(+) T cells <200/mm(3) or >500/mm(3) at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.