Abstract Body

Background: Previous randomised trials show patients switching to PI monotherapy maintain high rates of viral load (VL) suppression over 48-96 weeks, sometimes meeting VL non-inferiority criteria. However, longer-term resistance and toxicity risks are uncertain and the place of PI monotherapy in longterm management therefore remains controversial. Methodology: The Protease Inhibitor Versus Ongoing Triple-therapy (PIVOT) trial was a pragmatic 5-year prospective, randomised, controlled, open-label strategy trial in HIV-positive adults taking a stable NNRTI or PI-based regimen who had no previous VL failure and had VL<50 c/ml for ≥6months at trial entry. Patients were randomised to maintain ongoing triple therapy (OT) or switch to a PI monotherapy strategy (PIm) using a (physician selected)ritonavirboosted PI with prompt reintroduction of NRTIs if unable to maintain VL suppression <50 c/ml. VL was measured every 12 weeks, with resistance testing for all confirmed VL rebound ≥50 c/ml. Primary outcome was loss of future drug options, defined as new intermediate/high level resistance to ≥1 drug to which the patient’s virus was considered to be sensitive at trial entry. Secondary outcomes included serious disease complications (AIDS, serious non-AIDS, all-cause death), total grade 3/4 adverse events and neurocognitive function change (annual 5-test battery). All analyses were by ITT; non-inferiority margin 10%. Results: We randomised 587 patients (77% male, 68% white, 53% on NNRTI regimen at baseline) at 43 UK sites. Median (maximum) follow-up was 44 (59) months; 2.7% withdrew or were lost-to follow up. In PIm, 80% selected DRV/r, 14% LPV/r, 7% other PI/r. VL rebound was much more common in PIm; all rebounds on monotherapy re-suppressed either spontaneously or with NRTI reintroduction. Sequences were obtained for 83% of confirmed VL rebounds, but few new resistance mutations were seen in either arm. PIm was non-inferior on the primary outcome of loss of future drug options and there were no significant differences in serious disease complications, adverse events or neurocognitive function between the arms. 58% in PIm remained on monotherapy at the end of trial and overall drug costs were substantially lower in this arm. Conclusions: PI monotherapy, with prompt reintroduction of NRTIs for VL rebound, was a successful long-term management strategy, preserved future treatment options, was safe and well tolerated, and may be considered for more widespread use in long-term HIV care.