ACTG A5353: A pilot study of dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA < 500,000 copies/mL

Abstract

Background

Limited data exist on initial HIV-1 treatment with dolutegravir plus lamivudine , particularly for pre-treatment HIV-1 RNA >100,000 copies/mL.

Materials and Methods

A5353 is a phase II, single-arm, pilot study of once-daily dolutegravir (50mg) plus lamivudine (300 mg) in treatment-naïve 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 proportion with HIV-1 RNA < 50 copies/mL (FDA snapshot) at week 24. Virologic failure (VF) was confirmed HIV-1 RNA >400 copies/mL at week 16/20, or >200 copies/mL at/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 log10 copies/mL and 387 cells/mm ³. Virologic efficacy by FDA snapshot at week 24 was 108/120 (90%, CI [83%, 95%]) with comparable results in the >100,000 copies/mL and ≤100,000 copies/mL strata: 89% [75%, 97%] and 90% [82%, 96%], respectively. Three participants had VF, each with undetected plasma dolutegravir at ≥1 timepoints; the M184V reverse transcriptase and R263R/K integrase mutations developed in one participant. Two participants experienced Grade 3 possibly/probably treatment-related adverse events; none discontinued treatment due to adverse events.

Conclusion

Dolutegravir plus lamivudine demonstrated efficacy in individuals with pre-treatment HIV-1 RNA up to 500,000 copies/mL in this pilot trial, but a participant selected resistance mutations to lamivudine and dolutegravir