Evaluation of cerebrospinal fluid virological escape in patients on long-term protease inhibitor monotherapy

A strategy of protease inhibitor (PI) monotherapy with re-introduction of triple therapy in those who rebound has been shown to be a safe and effective treatment simplification approach for long-term management. We sought evidence for cerebrospinal fluid (CSF) virological escape in patients on long-term PI monotherapy. We performed lumbar puncture in asymptomatic participants with suppressed plasma HIV RNA after 96 weeks on the PI monotherapy arm (PI-mono) of the PIVOT trial. We also report CSF HIV RNA concentration in trial participants who were investigated for neurological/neurocognitive symptoms during the trial regardless of study arm allocation. All 11 asymptomatic participants on PI-mono who were tested had undetectable CSF HIV RNA at week 96. One of the three symptomatic participants on PI-mono had CSF HIV RNA of 1,895 copies/ml (undetectable in plasma) and neither of two symptomatic participants on triple therapy had CSF HIV RNA detected. CSF virological escape appears rare in asymptomatic patients on PI monotherapy and may not warrant routine CSF monitoring, but patients with symptoms merit more concern.