ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL.

Background. Limited data exist on initial human immunodeficiency virus type 1 (HIV-1) treatment with dolutegravir plus lamivudine. Methods. A5353 is a phase 2, single-arm, pilot study of once-daily dolutegravir (50 mg) plus lamivudine (300 mg) in treatment-naive participants with HIV-1 RNA >= 1000 and < 500 000 copies/mL. Exclusion criteria included active hepatitis B or major protease, reverse transcriptase, or integrase resistance. The primary efficacy measure was the proportion with HIV-1 RNA < 50 copies/mL (FDA [US Food and Drug Administration] Snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA > 400 copies/mL at week 16/20 or > 200 copies/mL at or after week 24. Dolutegravir levels and drug resistance testing were performed at VF. Results. One hundred and twenty participants (87% male, median age 30 years, 37 (31%) HIV-1 RNA > 100 000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log(10) copies/mL and 387 cells/mm(3). Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the > 100 000 copies/mL and <= 100 000 copies/mL strata, that is, 89% (75%, 97%) and 90% (82%, 96%), respectively. Three participants with VF, had undetected plasma dolutegravir at >= 1 time points; the M184V and R263R/K mutations developed in 1 participant. Two participants experienced grade 3 possible/probable treatment-related adverse events; none discontinued treatment due to adverse events. Conclusions. Dolutegravir plus lamivudine demonstrated efficacy in individuals with pretreatment HIV-1 RNA up to 500 000 copies/mL in this pilot trial, but a participant developed resistance mutations.