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Clin Infect Dis. 2018 May 17;66(11):1689-1697. doi: 10.1093/cid/cix1083.

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.

Author information

1
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois.
2
Department of Biostatistics.
3
Statistical Data Management Center, Harvard T H Chan School of Public Health, Boston, Massachusetts.
4
Division of Infectious Diseases, Rutgers University, New Brunswick, New Jersey.
5
BARC South Africa and Lancet Laboratories, Johannesburg, South Africa.
6
Division of AIDS, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryl.
7
Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
8
Department of Pharmacology and Toxicology, University of Alabama, Birmingham.
9
Department of Medicine, Vanderbilt University, Nashville, Tennessee.
10
ViiV Healthcare, Research Triangle Park, North Carolina.
11
Division of Infectious Diseases, Rush University, Chicago, Illinois.
12
Regional Center for Infectious Diseases, Cone Health, Greensboro, North Carolina.
13
Division of Infectious Diseases, Weill Cornell Medicine, New York, New York.

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.

PMID:
29253097
PMCID:
PMC5961075
[Available on 2019-05-17]
DOI:
10.1093/cid/cix1083

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