Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration

Townsend, Kerry; Meissner, Eric G.; Sidharthan, Sreetha; Sampson, Maureen; Remaley, Alan T.; Tang, Lydia; Kohli, Anita; Osinusi, Anu; Masur, Henry; Kottilil, Shyam

doi:10.1089/aid.2015.0170

Cited by 36 publications

(29 citation statements)

References 41 publications

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“…A study reported significantly lower levels of TC and higher levels of TG in coinfection compared with healthy controls, while another study reported significantly lower levels of large LDL but higher levels of large HDL particles and small HDL particles . Of note, many other studies as illustrated in Table ,B reported either lower or higher levels of lipids in coinfection compared with HIV monoinfection or HCV monoinfection or healthy controls, but the differences between the groups were either not statistically significant or the P values were not reported …”

Section: Resultsmentioning

confidence: 95%

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease

Osibogun

Ogunmoroti

Michos³

et al. 2017

Reviews in Medical Virology

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The incidence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection has been increasing with over 10 million people affected globally. The role biomarkers play as predictors of cardiovascular disease (CVD) risk among coinfected individuals is not well defined. We aimed to systematically review current evidence describing CVD biomarkers among individuals with HIV/HCV coinfection. We searched EMBASE, CINAHL, Google Scholar, PubMed, and Web of Science from inception to June 2017. MeSH terms and keywords were used to identify studies with information on HIV/HCV coinfection and CVD biomarkers (structural, functional, and serological) such as carotid intima-media thickness (CIMT), endothelial markers, C-reactive protein (CRP), homocysteine, and lipids. Among 332 articles screened, 28 were included (39,498 participants). Study designs varied: 18 cross-sectional, 9 cohort, and 1 clinical trial. Compared with healthy controls and people with HIV or HCV monoinfection, individuals with HIV/HCV coinfection had statistically significant lower levels of lipids and CRP and higher levels of endothelial markers (sICAM-1 and sVCAM-1), CIMT, homocysteine, and IL-6. One study found the odds of carotid plaque in coinfected individuals was 1.64 (0.91-2.94) compared with healthy controls, and another study showed the prevalence of vascular plaques (carotid and femoral) in coinfected individuals was higher compared with HIV monoinfected individuals (44% vs 14%, P = 0.04). Biomarkers of CVD have different patterns of association with HIV/HCV coinfection compared with monoinfection and healthy controls. Prospective studies are needed to confirm the predictive value of these biomarkers for clinical CVD risk among coinfected individuals.

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Section: Resultsmentioning

confidence: 95%

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease

Osibogun

Ogunmoroti

Michos³

et al. 2017

Reviews in Medical Virology

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“…This might explain a direct effect of HCV clearance on lipid metabolism. Townsend et al [13] reported a rapid increase in LDLc and TC values that was also sustained after treating HIV/HCV-coinfected patients with ledipasvir and sofosbuvir (LDV/SOF) combination therapy for 12 weeks. Thus, the increment in serum LDLc and TC levels occurs in both HIV/HCV-coinfected and HCV mono-infected patients.…”

Section: Discussionmentioning

confidence: 99%

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Sagheer

Soliman

Ahmad

et al. 2018

Libyan Journal of Medicine

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Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.

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“…HCV modulates host lipid metabolism as part of its natural lifecycle from virion entry, polyprotein processing and replication, to assembly and release . LDL‐C in HCV mono‐infected or HCV/HIV co‐infected patients treated with sofosbuvir plus ribavirin or sofosbuvir/ledipasvir therapy was correlated with a viral decline in serum titer, suggesting a direct influence of HCV clearance on serum cholesterol . However, the association between treatment and changes in lipid metabolism is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14][15] LDL-C in HCV monoinfected or HCV/HIV co-infected patients treated with sofosbuvir plus ribavirin or sofosbuvir/ledipasvir therapy was correlated with a viral decline in serum titer, suggesting a direct influence of HCV clearance on serum cholesterol. [16][17][18] However, the association between treatment and changes in lipid metabolism is unclear.…”

Section: Introductionmentioning

confidence: 99%

Emergence of drug resistance-associated variants and changes in serum lipid profiles in sofosbuvir plus ledipasvir-treated chronic hepatitis C patients

et al. 2017

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Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (<25%) of baseline NS5A RAVs, but 82.8% for patients with high frequency (>75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency <75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism.

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Interferon-Free Treatment of Hepatitis C Virus in HIV/Hepatitis C Virus-Coinfected Subjects Results in Increased Serum Low-Density Lipoprotein Concentration

Cited by 36 publications

References 41 publications

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease

A systematic review of the associations between HIV/HCV coinfection and biomarkers of cardiovascular disease

Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs

Emergence of drug resistance-associated variants and changes in serum lipid profiles in sofosbuvir plus ledipasvir-treated chronic hepatitis C patients

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