Clinical significance of transient HIV type-1 viraemia and treatment interruptions during suppressive antiretroviral treatment

Background Transient episodes of HIV type-1 viraemia are frequently observed in patients on suppressive combination antiretroviral therapy (cART). We studied the effect of such episodes and of treatment interruptions on clinical outcome and immunological response. Methods A total of 3,321 patients from the ATHENA cohort had virological suppression (HIV type-1 RNA400 copies/ml) viraemia and the outcomes death, AIDS or immunological response (CD4+ T-cell count increase ≥50% from 24 weeks) was studied with Poisson regression models, including either time-updated cumulative follow-up, time spent per type of episode or modelling episodes as binary status indicators. Results During 11,165 person-years of follow-up, 88 patients died, 111 developed AIDS and 2,019 had an immunological response. Longer follow-up time in treatment interruptions increased the risk of AIDS (relative risk [RR] 8.07, 95% confidence interval [CI] 3.98–16.4 per year longer) and impaired immunological response (RR 0.22, 95% CI 0.12–0.41). High-level viraemia was only associated with immunological response (RR 0.55, 95% CI 0.40–0.74), whereas low-level viraemia was not associated with any of the three outcomes. Status indicator models gave similar results. When also including time-updated CD4+ T-cell counts, the observed associations diminished. Conclusions Treatment interruptions and high-level, but not low-level, viraemia are strongly associated with clinical outcome, mainly via their effect on CD4+ T-cell counts.