Details

Autor(en) / Beteiligte

• Llibre, J M
• Cahn, P E
• Lo, J
• Barber, T J
• Mussini, C
• van Welzen, B J
• Hernandez, B
• Donovan, C
• Kisare, M
• Sithamparanathan, M
• van Wyk, J

Titel

Impact on inflammatory and atherogenesis biomarkers with the 2-drug regimen dolutegravir plus lamivudine in treatment-experienced people with HIV-1: A systematic literature review

Ist Teil von

• Antiviral therapy, 2021-12, Vol.26, p.1

Ort / Verlag

London: International Medical Press

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Objectives/aim: Even in the setting of sustained antiretroviral therapy (ART)-mediated virological suppression, HIV is associated with some persistent inflammation, contributing to an increased risk of non-AIDS-related comorbidities. HIV-associated inflammation may be driven by several factors including bacterial translocation, coinfections, and ongoing viral replication and persistence. Other host factors such as comorbidities and lifestyle characteristics may also contribute to inflammation. The 2-drug regimen dolutegravir plus lamivudine has demonstrated rapid viral load decline and durable, non-inferior efficacy compared with 3- and 4-drug regimens (3/4DRs) in both ART-naive and ART-experienced people with HIV-1 (PWH), with no differences in low-level viraemia, viral blips, or virological control in sanctuary sites and reservoirs. The objective of this systematic review was to summarize randomized controlled trial (RCT) and real-world evidence evaluating inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in treatment-experienced PWH. Methods: Ovid MEDLINE®, Embase®, PubMed, and Cochrane library databases were searched for studies published from 1 January 2013 to 14 July 2021. Additional searches were performed to identify relevant data presented at the 2021 International AIDS Society (IAS) Conference on HIV Science and IDWeek™ 2021. Eligible studies included real-world evidence and RCTs evaluating switch to dolutegravir plus lamivudine in treatment-experienced PWH aged ≥18 years that included data on CD4+/CD8+ ratio or inflammatory and atherogenesis biomarkers C-reactive protein, soluble CD14, interleukin-6, soluble CD163, D-dimer, fatty acid binding protein-2, or soluble vascular cell adhesion molecule-1. Results: Overall, 4 publications representing 2 RCTs (dolutegravir/lamivudine: SALSA, n=246; TANGO, n=369) and 6 publications of real-world evidence (dolutegravir plus lamivudine: n=1,000) were eligible for inclusion. All real-world studies evaluated CD4+/CD8+ ratio, while only 1 assessed inflammatory and atherogenesis biomarkers. Across both RCTs, no consistent pattern of change in biomarkers was observed between dolutegravir/lamivudine and 3/4DR comparators throughout the studies, with the exception of reductions in soluble CD14 (favoured dolutegravir/lamivudine in SALSA at week 48 and in TANGO at weeks 48 and 144) and IL-6 (favoured TAF-based regimens in TANGO at weeks 48 and 144; Figure 1). In the one real-world study evaluating changes in inflammatory biomarkers (n=67), median soluble CD14 levels significantly decreased at week 48 post-switch to dolutegravir plus lamivudine (P<0.001). Levels of other biomarkers (including IL-6) remained stable. In all of the real-world studies, increases in CD4+/CD8+ ratio were reported after switch to dolutegravir plus lamivudine (follow-up, 12-60 months). Conclusions/discussion: Evidence from 2 large RCTs and 1 real-world study showed no consistent impact on inflammatory and atherogenesis biomarkers with a switch to dolutegravir plus lamivudine versus 3/4DR comparators. Increases in CD4+/CD8+ ratio were also reported post-switch. These data suggest there is no evidence of an impact on inflammation after switching from a 3/4DR to dolutegravir/lamivudine. Future research on the clinical relevance and long-term consequences of changes in inflammatory biomarkers in PWH is needed.