This pragmatic, open-label UK study included adults with HIV who had viral load suppression (<50 copies per mL) for at least 24 weeks on combination antiretroviral therapy and a CD4 count of >100 cells/μL. They were randomised to either maintain their triple combination therapy or to switch to ritonavir-boosted protease inhibitor (PI) monotherapy (recommended darunavir or lopinavir), with prompt return to combination treatment if the viral load rebounded.
The primary outcome of the study - loss of future drug options – was defined as new intermediate-level or high-level resistance to one or more drugs in contemporary use (i.e. those present in UK treatment guidelines) to which the patient's virus was deemed to be sensitive at the start of the trial. The PI monotherapy arm was found to be non-inferior to the combination therapy group, as the upper limit of the two-sided 95% CI for the difference in proportions of patients meeting the primary endpoint was less than 10% (2 participants [0.7%] in the combination arm versus six [2.1%] in the PI monotherapy arm; difference 1.4% (−0.4 to 3.4). CD4 cell count increases and total HIV disease-related clinical events were similar between the two groups.
At the end of the study, 58% of patients randomised to PI monotherapy remained on this. Combination treatment was reintroduced mainly because of viral rebound (27% in total; 23% protocol-defined). Confirmed viral rebound (at least one episode) was documented in 8 patients (3.2%) in the combination group and 95 (35%) in the PI monotherapy group (absolute risk difference of 31.8%) – the authors say the difference was much greater than expected. They do however consider this outcome to be less informative in long-term strategy trials such as this, as aside from (negligible) risk of resistance; these brief episodes of low-level viraemia are unlikely to have adverse long-term clinical effects and were rapidly reversed by reintroduction of combination treatment.
The authors note that the observed low amount of resistance concurs with the results of previous trials of monotherapy, but extend these findings by providing longer-term outcome data from a large pragmatic trial needed to provide confidence in use of protease inhibitor monotherapy in clinical practice. They conclude that although there were high levels of viral load rebound, PI monotherapy does not appear to jeopardise future treatment options and they consider it an acceptable alternative to standard combination ART for long-term HIV management. They say their findings should be generalisable to settings where treatment is individualised and regular viral load monitoring is carried out.