Effects of active treatment discontinuation in patients with a CD4+ T-cell nadir greater than 350 cells/mm3: 48-week Treatment Interruption in Early Starters Netherlands Study (TRIESTAN).

Objective: To evaluate the safety and efficacy of discontinuing highly active antiretroviral therapy (HAART) in HIV-1-positive patients who initiated HAART at a CD4+ T-cell count >350 cells/mm.

Methods: Eligible patients were identified from the Dutch AIDS Therapy Evaluation, The Netherlands (ATHENA) national observational cohort. Interruption or continuation of HAART was offered to all.

Results: Of 71 patients enrolled, 46 (64%) interrupted HAART (STOP group) and 25 (36%) continued HAART (control group). The median CD4+ T-cell nadirs at the start of HAART were 469 (interquartile range [IQR]: 430-720) cells/mm3 and 510 (IQR: 440-637) cells/mm3, respectively. At week 48, the median plasma HIV RNA level in the STOP group had stabilized at approximately pre-HAART values (4.55 log10, IQR: 4.2-4.9 copies/mL), but the CD4+ T-cell count still exceeded the pre-HAART count (563 cells/mm3, IQR: 450-710 cells/mm3). Only 5 patients (11%) had reinitiated HAART after 48 weeks, all for personal reasons. No Centers for Disease Control and Prevention category events or death occurred after interruption. In 6 (13%) of 46 patients, mild symptoms of acute retroviral rebound syndrome (ARVS) were identified. No improvement was observed in mental or physical health scores. In 37% of patients, nonnucleoside reverse transcriptase inhibitor drug concentrations were still detectable 1 week after stopping.

Conclusions: Although HAART can safely be interrupted in patients with a high CD4 T-cell nadir, no improvement in quality of life was established. Patients can experience ARVS, the risk for development of resistance after treatment interruption is realistic, and there is a potential hazard of HIV transmission to sexual partners. We would not actively advise stopping treatment in patients who started treatment too early according to current guidelines.