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

Babafemi O. Taiwo*, Lu Zheng, Andrei Stefanescu, Amesika Nyaku, Baiba Bezins, Carole L. Wallis, Catherine Godfrey, Paul E. Sax, Edward Acosta, David Haas, Kimberly Y. Smith, Beverly Sha, Cornelius Van Dam, Roy M. Gulick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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 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 >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.

Original languageEnglish (US)
Pages (from-to)1689-1697
Number of pages9
JournalClinical Infectious Diseases
Volume66
Issue number11
DOIs
StatePublished - May 17 2018

Keywords

  • 2-drug therapy
  • dolutegravir
  • lamivudine
  • mutation
  • naive

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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