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 M Llibre; Pedro E Cahn; Janet Lo; Tristan J Barber; Cristina Mussini; Berend J van Welzen; Beatriz Hernandez; Cynthia Donovan; Michelle Kisare; Myooran Sithamparanathan; Jean van Wyk

doi:10.1093/ofid/ofac068

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

Open Forum Infect Dis. 2022 Feb 10;9(4):ofac068. doi: 10.1093/ofid/ofac068. eCollection 2022 Apr.

Authors

Affiliations

¹ Infectious Diseases, Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
² Fundación Huésped, Buenos Aires, Argentina.
³ Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Ian Charleson Day Centre, Royal Free London NHS Foundation Trust, London, United Kingdom.
⁵ Institute for Global Health, University College London, London, United Kingdom.
⁶ Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico, and University of Modena and Reggio Emilia, Modena, Italy.
⁷ University Medical Centre Utrecht, Utrecht, The Netherlands.
⁸ ViiV Healthcare, Madrid, Spain.
⁹ ViiV Healthcare, Research Triangle Park, North Carolina, USA.
¹⁰ GlaxoSmithKline, Nairobi, Kenya.
¹¹ ViiV Healthcare, Brentford, United Kingdom.

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.

Keywords: 2-drug regimen; HIV-1; dolutegravir plus lamivudine; inflammation.