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

Abstract

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 <500000 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 >100000 copies/mL) initiated study treatment. Median entry HIV-1 RNA and CD4 count were 4.61 log10 copies/mL and 387 cells/mm3. Virologic efficacy at week 24 was 108/120 (90%, confidence interval [83%, 95%]), with comparable results in the >100000 copies/mL and ≤100000 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 500000 copies/mL in this pilot trial, but a participant developed resistance mutations.

Clinical trials registration: NCT02582684.

Figure 1.

Consort diagram. *Number of screening instances and screening failure instances because of rescreening these numbers may not reflect people screened.

Figure 2.

Proportion (95% confidence interval) of participants with human immunodeficiency virus type 1 RNA levels <50 copies/mL by week (intention-to-treat/ missing/off treatment = ignored).

Figure 3.

HIV-1 RNA, DTG plasma concentration, and genotyping results for virologic failures and Snapshot nonsuccesses. Open circles represent HIV-1 RNA results that are less than the lower limit of quantification. Open diamonds represent drug level below the in vitro inhibitory concentration for 90% inhibition (IC90) (64 ng/mL) [17]. Participants 3, 4, and 5 had at least 1 time point with undetectable plasma DTG. Resistance mutations are shown at the time points tested, with “None” representing no mutation detected. Vertical dashed line represents discontinuation of study treatment. Horizontal dashed line represents HIV-1 RNA 50 copies/mL. Abbreviations: DTG, dolutegravir; HIV-1, human immunodeficiency virus type 1.