Reduced soluble CD14 levels after switching from a dual regimen with lamivudine plus boosted protease inhibitors to lamivudine plus dolutegravir in virologically suppressed HIV-infected patients

Abstract

Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients.

Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid–binding protein (I-FABP) and D-dimer.

Methods: We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (−48 W) and 48 weeks after switch (+48 W).

Results: A total of 67 patients were included. Median sCD14 levels were stable from −48 W to BL (from 6.07 to 6.04 log₁₀ pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84–6.07) log₁₀ pg/mL at + W48 (p < 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG.

Conclusions: In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications.

Keywords:

• HIV
• inflammation
• inflammatory biomarkers
• dual therapy
• dolutegravir
• sCD14

Acknowledgments

We would like to thank Dr Arianna Emiliozzi, Dr Chiara Picarelli, Dr Davide Moschese and Dr Alex Dusina from Catholic University of Sacred Heart, Institute of Clinical Infectious Diseases, Rome, for their contribution in data collection.

Disclosure statement

A.B. has received nonfinancial support from Bristol-Myers Squibb and ViiV Healthcare, and personal fees from Gilead Sciences. G. B. has received a travel grant from Bristol-Myers Squibb. R. C. has been an advisor for Gilead, Janssen-Cilag and Basel Pharmaceutical, has received speakers’ honoraria from ViiV Healthcare, Bristol-Myers Squibb, Merck Sharp & Dohme, Abbott, Gilead and Janssen-Cilag, and has received research support from ‘Fondazione Roma’. M.F. received speakers’ honoraria and support for travel to meetings from Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen-Cilag, ViiV Health Care and Gilead. S. D. G. was a paid consultant or member of advisory boards for Gilead, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and Bristol-Myers Squibb. All other authors: none to declare.

Additional information

Funding

This work was supported by internal funding.

Notes on contributors

Francesca Lombardi

Dr. Francesca Lombardi received Degree in Biology, Sapienza University of Rome; specialist degree in “Clinical Biochemistry” at University of Rome “Tor Vergata”. She worked at Children’s Hospital Los Angeles from 2009 to 2011, her main interests of research was HIV. Since 2012 she has worked at the Institute of “Clinical Infectious Diseases” at Catholic University of Sacred Heart of Rome in the HIV research field, participating in randomized clinical trials and performing observational studies mainly focused on antiretroviral therapy.

Simone Belmonti

Dr. Simone Belmonti is a Clinical Laboratory Technologist, graduated from Sapienza University of Rome. He worked at the Italian National Institute of Health and San Raffaele Scientific Institute, Milan, and since 2011 he has been a member of the HIV research team at the Institute of “Clinical Infectious Diseases” at Catholic University of Sacred Heart of Rome.

Alberto Borghetti

Dr. Alberto Borghetti graduated in Medicine and Surgery at Catholic University of Sacred Heart of Rome in 2012 and became specialist in Infectious Diseases in 2019. Since 2012 he has worked in the field of HIV research and clinic, participating in randomized clinical trials and performing observational studies mainly focused on antiretroviral therapy and management of chronic HIV infection. Since 2019 he has worked as an Infectious Diseases consultant in medical and surgical wards at Fondazione Policlinico A. Gemelli in Rome, while continuing his research activity on HIV.

Arturo Ciccullo

Dr. Arturo Ciccullo is a resident in infectious diseases and tropical medicine at Catholic University of the Sacred Heart in Rome since 2016. He received his degree in Medicine and Surgery there in 2015. At the moment, his research activity mainly focuses on HIV infection management and antiretroviral therapy. He authored 20 publications in international peer-reviewed journals.

Gianmaria Baldin

Dr. Gian M. Baldin graduated at University of Padua, Italy, in 2014 and became specialist in Infectious and Tropical Diseases at Catholic University of Sacred Heart in 2018. His research interests are HIV antiretroviral therapy. He performed a trainee in Ikonda hospital in Tanzania from October to December 2017.

Roberto Cauda

Dr. Roberto Cauda MD, is the Chairman of Infectious Diseases and Director of Specialisation School in Infectious Diseases and Tropical Medicine at Catholic University of Sacred Heart of Rome, Fondazione Policlinico A. Gemelli. Adjunct Professor at the University of Alabama in Birmingham, and Texas Tech University. Visiting Professor in Slovak Universities; honorary fellow of ESCMID, Royal Society of Tropical Medicine and Hygiene, ESBIC. Research: antibiotic resistance and nosocomial infections, clinical and epidemiological aspects of HIV infection/disease, viral hepatitis, herpetic and tropical diseases.

Massimiliano Fabbiani

Dr. Massimiliano Fabbiani graduated in Medicine and Surgery at University of Siena in 2003 and became specialist in Infectious Diseases there in 2007. He obtained his PhD in biological and clinical research on infectious and tropical disease. He was Infectivology Physician at Catholic University of Sacred Heart of Rome and later San Gerardo Hospital, University of Milano-Bicocca, Monza. Currently he works at the Clinic of Infectious and Tropical Diseases of Foundation IRCCS Polyclinic San Matteo-University of Pavia.

Simona Di Giambenedetto

Simona Di Giambenedetto MD, graduated in Medicine and Surgery at Catholic University of Sacred Heart of Rome in 1998. She obtained the title of specialist in Infectious Diseases in 2003. From 2004 to 2008 she worked as a MD with a contract at the Institute of “Clinical Infectious Diseases” at Policlinico Gemelli and since 2009 she has worked as a Clinical Researcher at the Institute of “Clinical Infectious Diseases” at Catholic University of Sacred Heart of Rome. Her research activity is predominantly focused on HIV infection, opportunistic infections in AIDS and antiretroviral therapy.