The long-term consequences of this viral rebound and re-suppression are unknown. There were no differences in the frequency of emergence of viral resistance, or of High Content Screening serious adverse events, although few patients developed drug resistance and thus confidence in the estimate of this effect is low. One potential
concern is the development of CNS disease in patients on PI monotherapy [6, 11]; however, we did not identify a difference in this outcome although the quality of the evidence is low. Further data are required. Overall, there is no significant clinical benefit of PI monotherapy compared with standard combination ART, which might offset the disadvantage of a lower rate of viral suppression with PI monotherapy. For this reason PI monotherapy should not be used in unselected patient populations for maintaining virological suppression where standard ART is an acceptable alternative. There may be potential benefits of PI monotherapy, in terms of drug resistance, long-term drug toxicity and cost  but further data are required. The ongoing ‘Protease Inhibitor monotherapy vs. Ongoing Triple therapy in the long-term management of HIV infection’ (PIVOT) trial has been designed to address see more these issues . The primary endpoint is drug resistance. We recognize that PI monotherapy may well be an acceptable option in some specific patient populations but there
are few data to provide recommendations. Clinicians might consider PI monotherapy in patients who are unable to tolerate NRTIs due to toxicities or as a short-term measure to manage or bridge complex clinical scenarios (e.g. stopping certain NNRTI-containing regimens or managing toxicity overdose or acute illness). Where PI monotherapy is considered, DRV/r (dosed once or twice daily) or LPV/r (dosed twice daily) should be used. ATV/r monotherapy BCKDHB is not recommended as it has been associated with higher rates of virological failure [17, 18]. PI monotherapy is not recommended
in patients with active hepatitis B coinfection. We recommend against treatment interruption or intermittent therapy in patients stable on a virally suppressive ART regimen (1A). Proportion of patients with a CD4 cell count <350 cells/μL not on ART. Several RCTs have investigated the efficacy of CD4 cell count-guided intermittent therapy as a potential strategy to reduce long-term risk of drug toxicity and drug resistance [1-4]. In the largest of these, patients were randomly allocated to either CD4 cell count-guided intermittent therapy (stopping ART once CD4 cell count >350 cells/μL, restarting when CD4 cell count falls to 250 cells/μL) compared with a continuous ART . The trial showed intermittent therapy was associated with a significantly higher rate of opportunistic disease and all-cause mortality and a higher rate of major cardiovascular, renal or hepatic disease. The effect was seen at all CD4 cell count levels.