Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy-Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review

Josep Llibre, Pedro Cahn, Janet Lo, Tristan Barber, Cristina Mussini, Berend van Welzen, Beatriz Hernadez, Cynthia Donovan, Michelle Kisare, Myooran Sithamparanathan, Jean Van Wyk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background. The 2-drug regimen dolutegravir plus lamivudine has demonstrated long-term noninferior efficacy vs 3-/4-drug regimens (3/4DRs) in phase 3 trials. This systematic literature review summarizes clinical trial and real-world evidence evaluating impact of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with human immunodeficiency virus type 1 (PWH). Methods. Using Ovid MEDLINE, Embase, PubMed, and Cochrane library databases and conference proceedings, we searched for studies published from 1 January 2013 to 14 July 2021, reporting changes in inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in antiretroviral therapy–experienced, virologically suppressed PWH aged ≥18 years. Results. Four records representing 2 randomized controlled trials (RCTs) and 6 records of real-world evidence met eligibility criteria. All real-world studies evaluated CD4 +/CD8 + ratio, while only 1 assessed inflammatory biomarkers. Across both RCTs, no consistent pattern of change in biomarkers was observed between dolutegravir/lamivudine and 3/4DR comparators. There were significant changes in soluble CD14 favoring dolutegravir/lamivudine in TANGO at weeks 48 and 144 and SALSA at week 48, and in interleukin-6 favoring the control group in TANGO at weeks 48 and 144. In the real-world study evaluating inflammatory biomarkers, median soluble CD14 significantly decreased 48 weeks postswitch to dolutegravir plus lamivudine (P < .001), while other biomarkers remained stable. In all 6 real-world studies, increases in CD4 +/CD8 + ratio were reported after switch to dolutegravir plus lamivudine (follow-up, 12–60 months). Conclusions. Results show that dolutegravir plus lamivudine has a comparable impact on inflammatory and atherogenesis biomarkers vs 3/4DRs, with no consistent pattern of change after switch in virologically suppressed PWH.

Original languageEnglish
Article numberofac068
Pages (from-to)1-9
JournalOpen Forum Infectious Diseases
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 2022

Keywords

  • 2-drug regimen
  • HIV-1
  • dolutegravir plus lamivudine
  • inflammation

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