Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death.

OBJECTIVES: The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death.

METHODS: Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models.

RESULTS: Of 3811 patients included in the study, 26% were ART-naïve prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/microL and the median viral load was 4.36 log(10) HIV-1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS-events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non-TI group [IRR 2.63; 95% confidence interval (CI) 2.01-3.44; P<0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count- and viral load-adjusted IRR was 1.14 (95% CI 0.86-1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of <200 cells/microL had a 3-fold higher risk of AIDS/death than those with a CD4 cell count of 200-350 cells/microL, whereas patients with a current CD4 cell count of >350 cells/microL had a 4-fold lower risk of disease progression.

CONCLUSIONS: TI is common in clinical practice. The risk of AIDS/death increased more than 2-fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs.