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

Francesca Lombardi, Simone Belmonti, Alberto Borghetti, Arturo Ciccullo, Gianmaria Baldin, Roberto Cauda, Massimiliano Fabbiani, Simona Di Giambenedetto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)92-98
Number of pages7
JournalHIV Research and Clinical Practice
Volume20
Issue number3
DOIs
Publication statusPublished - May 4 2019

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

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. / Lombardi, Francesca; Belmonti, Simone; Borghetti, Alberto; Ciccullo, Arturo; Baldin, Gianmaria; Cauda, Roberto; Fabbiani, Massimiliano; Di Giambenedetto, Simona.

In: HIV Research and Clinical Practice, Vol. 20, No. 3, 04.05.2019, p. 92-98.

Research output: Contribution to journalArticle

Lombardi, Francesca ; Belmonti, Simone ; Borghetti, Alberto ; Ciccullo, Arturo ; Baldin, Gianmaria ; Cauda, Roberto ; Fabbiani, Massimiliano ; Di Giambenedetto, Simona. / 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. In: HIV Research and Clinical Practice. 2019 ; Vol. 20, No. 3. pp. 92-98.
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T1 - 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

AU - Lombardi, Francesca

AU - Belmonti, Simone

AU - Borghetti, Alberto

AU - Ciccullo, Arturo

AU - Baldin, Gianmaria

AU - Cauda, Roberto

AU - Fabbiani, Massimiliano

AU - Di Giambenedetto, Simona

PY - 2019/5/4

Y1 - 2019/5/4

N2 - 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.

AB - 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.

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