Long-Term CD4+ T-Cell Response to Highly Active Antiretroviral Therapy According to Baseline CD4+ T-Cell Count

Abstract

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: 3, 200–349 cells/mm³, 350–499 cells/mm³, and ≥500 cells/mm³. The main outcome measures were proportion of patients with CD4⁺ T cells 500/mm³ at last determination and rate of CD4⁺ T-cell recovery. Patients were followed-up 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/mm³ (IQR, 90–355) to 499 cells/mm³ (IQR, 312–733) (P < 0.001). Compared with the group with a baseline CD4⁺ T-cell count of ≥500/mm³, the relative risk of having a last determination of CD4⁺ T-cell counts >200 cells/mm³ was 0.79 (95% CI, 0.75–0.83), 0.92 (95% CI, 0.89–0.96) and 1 for baseline CD4⁺ T cells 500 cells/mm³ 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 3, 200–349 cells/mm³, and 350–499 cells/mm³, respectively, compared with a baseline CD4⁺ T-cell count of ≥500 cells/mm³. 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 3 have poorer immunologic outcome as measured by the proportion of patients with CD4⁺ T cells 500/mm³ 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.