Research in context
Evidence before this study
There is an ongoing need for simplification of combination antiretroviral therapy (ART), preferably with nucleotide-sparing regimens. Dolutegravir has a high genetic barrier to resistance and, therefore, might be suitable as maintenance monotherapy, as suggested by findings from a small case series. We searched PubMed between Sept 1, and Dec 8, 2014, using the terms “dolutegravir” AND “monotherapy” AND “randomi*”, with inclusion of English-language articles only. We found no substantive evidence from published randomised trials of maintenance of virological suppression with dolutegravir monotherapy compared with combination ART.
Added value of this study
We aimed to show that dolutegravir monotherapy was non-inferior to combination ART for maintaining virological suppression in 104 patients with HIV-1 infection who had been successfully treated with combination ART, had HIV RNA zeniths of 100 000 copies per mL or less, and CD4 nadirs of 200 cells per μL or higher. We found that dolutegravir monotherapy was non-inferior to combination ART at 24 weeks: an HIV RNA viral load of 200 copies per mL or higher was observed in one of 50 patients who switched to dolutegravir monotherapy immediately and none of the 53 patients who switched after 24 weeks of continued combination ART (difference 2%, 95% CI −5 to 12). However, new mutations associated with resistance in the integrase gene were detected in three patients, and virological failure was eventually observed in eight of the 95 patients who started dolutegravir monotherapy.
Implications of the available evidence
Despite promising findings from an observational case series, our results clearly show that dolutegravir should not be used as maintenance monotherapy. Investigators in ongoing studies of dolutegravir monotherapy should strongly reconsider their study design and inform their institutional review boards and patients about these results.