Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA)

Taramasso, Lucia; Tatarelli, Paola; Ricci, Elena; Madeddu, Giordano; Menzaghi, Barbara; Squillace, Nicola; Socio, Giuseppe Vittorio De; Martinelli, Canio; Gulminetti, Roberto; Maggi, Paolo; Orofino, Giancarlo; Vichi, Francesca; Biagio, Antonio Di; Bonfanti, Paolo

doi:10.1186/s12879-018-3268-5

Cited by 49 publications

(37 citation statements)

References 27 publications

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“…Although some mild-to-moderate biochemical abnormalities have been pinpointed as RPV-related adverse hepatic events, these alterations are soon normalised 20. Overall, clinical evidence supports the use of RPV in lifelong treatments, with some recent reports even suggesting its beneficial effects on several clinical parameters after switching from other non-RPV-containing regimens 21 22. However, its particular contribution to liver disease progression and its actions on different cell subpopulations under varying pathological hepatic conditions were unknown previously to the present study.…”

Section: Discussionsupporting

confidence: 67%

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells

Martí-Rodrigo

Alegre

Moragrega

et al. 2019

Gut

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ObjectiveLiver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.DesignThe effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms.ResultsRPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism.ConclusionRPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV’s actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.

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Section: Discussionsupporting

confidence: 67%

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells

Martí-Rodrigo

Alegre

Moragrega

et al. 2019

Gut

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“…Its use is recommended to be limited to patients with pre-treatment CD4 counts exceeding 200 cells/mm 3 [2,3]. RPV has fewer reported neurologic and psychiatric adverse effects compared with efavirenz (EFV) [7], and a more favourable metabolic profile compared with protease inhibitors, making it an attractive third drug in combination with NRTIs [8]. The combination of ABC/3TC plus RPV is a once-daily regimen with low pill burden [7].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-naïve HIV-1 infected adults

Wong

et al. 2020

AIDS Res Ther

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Background: The anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients. Methods: A retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial antiretroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events. Results: 170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14-24) weeks in the RPV group, and 21 (13-26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure. Conclusion: RPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.

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“…However, in a previous study, the switch from ritonavir to cobicistat was followed by a significant reduction in TC, LDL, but also of HDL, and TG levels in patients with HC [14]. In our prospective observation, despite most patients were switching from ritonavir boosted PI to DRV/c, we did not observe significant change in lipids, even in the sub-analysis focused on patients with higher baseline triglycerides and cholesterol levels, which were those expected to experience the greatest lipid changes [14, 21]. These results were consistent with previous studies including a large proportion of patients on ritonavir-boosted PI regimens who switched to DRV/c [12, 16], although lipid changes could have been partially confounded by the presence or removal of tenofovir disoproxil fumarate (TDF) from the regimen after the switch, with consequent lost of its lipid lowering effect [22].…”

Section: Discussionmentioning

confidence: 90%

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohort (SCOLTA)

et al. 2019

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Background: Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. Methods: Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. Results: A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13-20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. Conclusions: DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.

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Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA)

Cited by 49 publications

References 27 publications

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells

Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells

Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-naïve HIV-1 infected adults

Positioning of darunavir/cobicistat-containing antiretroviral regimens in real life: results from a large multicentre observational prospective cohort (SCOLTA)

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