Background: The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function.
Methods: This was a randomized 144-week follow-up CD4⁺ T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA<50 copies/ml, CD4⁺ T-cell count >500 cells/μl and nadir CD4⁺ T-cell count >100 cells/μl were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4⁺ T-cell count decreased to <350 cells/μl. The primary end points were AIDS-defining illnesses, death, CD4⁺ T-cell count <200 cells/μl, or virological failure after restarting ART.
Results: A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4⁺ T-cell count significantly decreased in the TI group (even in patients with persistently high CD4⁺ T-cell counts and no clinical events) versus the CT group (median change -408 cells/μl versus -21.5 cells/μl; P<0.001), whereas a significant increase in CD8⁺ T-cell count was observed (256 cells/μl versus -59 cells/μl; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4⁺ T-cell counts.
Conclusions: Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4⁺ T-cell count.