Comparable viral decay with initial dolutegravir plus lamivudine versus dolutegravir-based triple therapy

Abstract

Objectives: To expand understanding of the virological potency of initial dolutegravir plus lamivudine dual therapy (dolutegravir/lamivudine), we compared the viral decay seen in the pilot ACTG A5353 study with the decay observed with dolutegravir plus two NRTIs in the SPRING-1 and SINGLE studies, while also exploring the impact of baseline viral load (VL). Methods: Change in VL from baseline was calculated for timepoints shared by A5353 (n"120, including 37 participants with pretreatment VL .100000 copies/mL), SPRING-1 (n"51) and SINGLE (n"417). The 95% CIs of change from baseline were determined for each observed week, using the mean log10-transformed VL, and compared between the dolutegravir/lamivudine and triple therapy groups using the Wilcoxon Rank Sum test for non-inferiority (d"0.5). To assess the impact of baseline VL on viral decay, we examined a bi-exponential non-linear mixed-effect model. Results: The mean VL change from baseline to week 24 was #2.9 log10 copies/mL for dolutegravir/lamivudine versus #3.0 log10 copies/mL for dolutegravir-based three-drug therapy (P,0.001). In the decay model, baseline VL .100000 copies/mL was associated with a slower initial decay rate (d1). A faster initial decay rate was seen with dolutegravir/lamivudine, which was partially offset when baseline VL was .100000 copies/mL as indicated by a significant interaction between baseline VL and drug therapy group. The secondary decay rate (d2) was not significantly different from zero, with no significant associations. Conclusions: Viral decay with dolutegravir/lamivudine was comparable to viral decay with dolutegravir-based triple therapy, even in individuals with higher pretreatment VL (.100000 copies/mL).