• Humans
• Male
• Female
• Liver Cirrhosis
• HIV Infections/complications
• HIV Infections/drug therapy
• Antiviral Agents/therapeutic use
• Middle Aged
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Prognosis
• Coinfection/drug therapy
• Disease Progression
• Sustained Virologic Response
• Spain/epidemiology
• Adult
• Liver Neoplasms
• Carcinoma, Hepatocellular/virology
• Retrospective Studies
• Incidence

• Consommateurs de drogues
• Injection
• Lignes directrices
• UDI
• VHC
• VIH

• Drogenkonsumenten
• HCV
• HIV
• Injektion
• Injizieren
• Leitlinien
• PWID

• Humans
• Hepacivirus
• Hepatitis C/drug therapy
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/diagnosis
• Renal Insufficiency, Chronic/therapy

• Direct-acting antiviral agents (DAAs)
• hepatitis C virus (HCV)
• people living with HIV (PLWH)

• Aged
• Antiviral Agents/therapeutic use
• Coinfection/complications
• Coinfection/drug therapy
• Female
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• Hepacivirus
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Male
• Medicare
• United States/epidemiology

• R01 AG055636 NIA NIH HHS

We assessed the prevalence of anti‐hepatitis C virus (HCV) antibodies and active HCV infection (HCV‐RNA‐positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015–2018.

The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation.

The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)‐positive (78.7% were prior injection drug users); 29 were HCV‐RNA‐positive (2.2%). Of the 29 HCV‐RNA‐positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV‐RNA‐positive patients and 68 (23.4%) of those who cleared HCV after anti‐HCV therapy (p = 0.04). The prevalence of anti‐HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti‐HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001).

In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct‐acting antiviral agents, HCV‐related cirrhosis remains significant in this population.

• HIV infection/*epidemiology
• coinfection/*epidemiology
• hepatitis C/drug therapy/*epidemiology

• Daclatasvir
• HCV
• HIV
• Real-world
• Sofosbuvir

• CD4-positive T lymphocytes
• HIV
• T cell
• antigen
• coinfection
• hepatitis C
• immune reconstitution
• receptors

• Antiretroviral Therapy, Highly Active
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes
• Coinfection/drug therapy
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV-1
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Humans

• R37 DA013806 NIDA NIH HHS
• R01 DA016078 NIDA NIH HHS
• UL1 TR000424 NCATS NIH HHS
• R01 AI116868 NIAID NIH HHS
• R01 DA013806 NIDA NIH HHS
• T32 AI007291 NIAID NIH HHS
• T32 GM136577 NIGMS NIH HHS

• CD4 T cells
• CD4/CD8 ratio
• CD8 T cells
• Direct-acting antiviral agents
• HIV infection
• Hepatitis C virus
• Soluble CD14
• Sustained viral response

To evaluate the impact of hepatitis C virus (HCV) elimination via interferon (IFN)-based therapy on gene expression profiles related to the immune system in HIV/HCV-coinfected patients.

We conducted a prospective study in 28 HIV/HCV-coinfected patients receiving IFN-based therapy at baseline (HIV/HCV-b) and week 24 after sustained virological response (HIV/HCV-f). Twenty-seven HIV-monoinfected patients (HIV-mono) were included as a control. RNA-seq analysis was performed on peripheral blood mononuclear cells (PBMCs). Genes with a fold-change (FC) ≥ 1.5 (in either direction) and false discovery rate (FDR) ≤ 0.05 were identified as significantly differentially expressed (SDE).

HIV/HCV-b showed six SDE genes compared to HIV-mono group, but no significantly enriched pathways were observed. For HIV/HCV-f vs. HIV/HCV-b, we found 58 SDE genes, 34 upregulated and 24 downregulated in the HIV/HCV-f group. Of these, the most overexpressed were CXCL2, PDCD6IP, ATP5B, IGSF9, RAB26, and CSRNP1, and the most downregulated were IFI44 and IFI44L. These 58 SDE genes revealed two significantly enriched pathways (FDR < 0.05), one linked to Epstein-Barr virus infection and another related to p53 signaling. For HIV/HCV-f vs. HIV-mono group, we found 44 SDE genes that revealed 31 enriched pathways (FDR < 0.05) related to inflammation, cancer/cell cycle alteration, viral and bacterial infection, and comorbidities associated with HIV/HCV-coinfection. Five genes were overrepresented in most pathways (JUN, NFKBIA, PIK3R2, CDC42, and STAT3).

HIV/HCV-coinfected patients who eradicated hepatitis C with IFN-based therapy showed profound gene expression changes after achieving sustained virological response. The altered pathways were related to inflammation and liver-related complications, such as non-alcoholic fatty liver disease and hepatocellular carcinoma, underscoring the need for active surveillance for these patients.

The online version contains supplementary material available at 10.1186/s12929-021-00718-6.

• Gene expression
• HCV clearance
• HIV/HCV coinfection
• Immune system
• Interferon therapy
• PBMCs

Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis.

Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay.

Results: We found significant decreases in severity scores of liver disease [LSM (q-value < 0.001), HVPG (q-value = 0.011), and CTP (q-value = 0.045)] and plasma biomarkers [LBP (q-value < 0.001), IP-10 (q-value < 0.001), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), IL-1RA (q-value = 0.013), OPG (q-value < 0.001), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), PAI-1 (q-value = 0.001), and VEGF-A (q-value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP (q-value < 0.001), IP-10 (q-value < 0.001), MCP-1 (q-value = 0.008), IL-8 (q-value < 0.001), IL-18 (q-value < 0.001), OPG (q-value = 0.004), sVCAM-1 (q-value < 0.001), sICAM-1 (q-value < 0.001), and PAI-1 (q-value = 0.002). For CTP values, we found significant positive associations with IP-10 (q-value = 0.010), IL-6 (q-value = 0.010), IL-1RA (q-value = 0.033), and sICAM-1 (q-value = 0.010).

Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.

• HIV/HCV co-infected patients
• angiogenesis
• chronic hepatitis C (CHC)
• cirrhosis
• coagulopathy
• direct-acting antiviral (DAA) therapy
• inflammation

• Consensus
• DAA
• HCV
• Hepatitis C
• TASL
• Taiwan

• Adolescent
• Antiviral Agents/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/therapy
• Child
• Coinfection/drug therapy
• Consensus
• Female
• Hepacivirus
• Hepatitis C/complications
• Hepatitis C/drug therapy
• Hepatitis C/epidemiology
• Hepatitis C, Chronic/drug therapy
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/epidemiology
• Pregnancy
• Taiwan/epidemiology

• Biomarkers
• Chronic hepatitis C
• HCV therapy
• HIV
• Immune activation
• Inflammation

Background

It is estimated that approximately 10 million individuals in Pakistan are infected with hepatitis C virus (HCV). Historically, it was very difficult not just to cure but even treat HCV as available options did not have desirable outcomes. However, the approval of directly acting antiviral (DAA) drugs has revolutionized treatment and management. These are specific proteases and polymerase inhibitors with profound capability for accomplishing elimination and overtime eradication of the virus.

Objective

The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF) in combination with ribavirin (RIB) for the treatment of chronic hepatitis C virus with genotype 3.

Materials and methods

This prospective observational study was conducted at the gastroenterology section of Medical Unit IV, Jinnah Post-graduate Medical Center, Karachi and Medical Unit II, Dow University of Health Sciences, Ojha Campus, Karachi from January 2016 to December 2016. Patients aged 18 years or older of either gender having chronic active HCV infection as demonstrated by a positive Anti-HCV (ELISA) test and a qualitative polymerase chain reaction (PCR) analysis along with genotype analysis showing only type 3 were inducted into the study.

Treatment was initiated with either 12-week or 24-week regimen of SOF 400 mg once daily along with weight-adjusted RIB orally. Successful treatment was indicated by the elimination of the virus, i.e., undetectable viral load/levels by PCR qualitative analysis. Rapid virological response (RVR), end of treatment response (ETR), and sustained virological response (SVR) were defined as the undetectable viral load at four, 12, and 24 weeks, respectively.

Results

A total of 300 patients were inducted into the study, predominantly female (57%). The mean age of presentation was 41.14 ± 11.48, and most (70.33%) were treatment naïve. The mean alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels at presentation were 41.89 ± 46.23 IU/l, 68.57 ± 83.62 IU/l, and 54.52 ± 77.57 IU/l, respectively.

ALT, AST, and GGT levels at 24 weeks were 33.84 ± 13.60 IU/l, 32.44 ± 16.16 IU/l, and 37.59 ± 22.41 IU/l, respectively, showing significant improvement. ETR was achieved in 99.1% (209) treatment-naïve patients and 98.9% (88) treatment-experienced patients. SVR rates were almost similar with 98% (208) achieving it in the treatment-naïve group and 96.6% (86) achieving it in the treatment-experienced group.

Conclusion

SOF in combination with RIB is safe and remarkably efficacious in the treatment of chronic HCV, genotype 3. Not only is this regimen associated with the elimination of viral replication but it also improved transaminase levels. Outcomes are rarely, if ever, affected by previous use of antiviral medications.

• chronic hepatitis c
• efficacy
• genotype 3
• ribavirin
• safety
• sofosbuvir

The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study.

HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates.

1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4–49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2–6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders.

Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

• Adult
• Antiviral Agents/therapeutic use
• Coinfection/diagnostic imaging
• Coinfection/drug therapy
• Coinfection/mortality
• Elasticity Imaging Techniques
• Female
• France
• HIV Infections/diagnostic imaging
• HIV Infections/drug therapy
• HIV Infections/mortality
• Hepatitis C, Chronic/diagnostic imaging
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/mortality
• Humans
• Liver/diagnostic imaging
• Male
• Middle Aged
• Mortality
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Sustained Virologic Response

• EQ-5D
• HIV
• direct acting antivirals
• health-related quality of life
• hepatitis C

Background: Advanced cirrhosis is related to alterations in immunity. We aimed to evaluate the levels of peripheral CD4⁺ T cells (Tregs) and plasma cytokine in patients coinfected with human immunodeficiency virus and hepatitis C virus (HIV/HCV) according to liver fibrosis stages [evaluated as liver stiffness measure (LSM)] and their linear relationship. Methods: We performed a cross-sectional study on 238 HIV/HCV-coinfected patients (119 had <12.5 kPa, 73 had 12.5–25 kPa, and 46 had >25 kPa). Peripheral T-cell subsets were phenotyped by flow cytometry, plasma biomarkers were assessed by multiplex immunoassays, and LSM was assessed by transient elastography. Results: We found HIV/HCV-coinfected patients had higher values of CD4⁺ Tregs (p < 0.001), memory Tregs (p ≤ 0.001), and plasma cytokine levels [IFN-γ (p ≤ 0.05) and IL-10 (p ≤ 0.01)] compared with healthy donors and HIV-monoinfected patients. In the multivariate analysis, higher LSM values were associated with reduced levels of IL-10 (adjusted arithmetic mean ratio (aAMR) = 0.83; p = 0.019), IL-2 (aAMR = 0.78; p = 0.017), TNF-α (aAMR = 0.67; p < 0.001), and IL-17A (aAMR = 0.75; p = 0.006). When we focus on HIV/HCV-coinfected patients analyzed by LSM strata, patients with ≥25 kPa had lower values of IL-2 (aAMR = 0.66; p = 0.021), TNF-α (aAMR = 0.565; p = 0.003), and IL-17A (aAMR = 0.58; p = 0.003) than patients with <12.5 kPa. Conclusion: HIV/HCV-coinfected patients showed an immunosuppressive profile compared to healthy controls and HIV-monoinfected patients. Additionally, HIV/HCV-coinfected patients with advanced cirrhosis (LSM ≥ 25 kPa) had the lowest plasma values of cytokines related to Th1 (IL-2 and TNF-α) and Th17 (IL-17A) response.

• HIV
• Treg cells
• chronic hepatitis C
• cirrhosis
• cytokines
• immune dysfunction

Chronic infections are a major factor in the development of pulmonary embolism (PE). We aimed to evaluate the trends of PE-related hospitalizations and PE-related deaths in people living with HIV (PLWH) during the era of combination antiretroviral therapy (cART) through a retrospective study in Spain. Data were collected from the Minimum Basic Data Set (MBDS) between 1997 and 2013. The study period was fragmented into four calendar periods (1997–1999, 2000–2003, 2004–2007, and 2008–2013). The rate of PE-related hospitalizations remained stable in PLWH (P = 0.361). HIV-monoinfected patients had a higher incidence than HIV/HCV-coinfected patients during all follow-up [(98.7 (95%CI = 92.2; 105.1); P < 0.001], but PE incidence decreased in HIV-monoinfected patients (P < 0.001) and increased in HIV/HCV-coinfected patients (P < 0.001). Concretely, the rate of PE-related hospitalizations decreased significantly in patients monoinfected with HIV [from 203.6 (95%CI = 175.7; 231.6) events per 100,000 patient-years in 1997–1999 to 74.3 (95%CI = 66.1; 82.3) in 2008–2013; P < 0.001], while patients coinfected with HIV/HCV had a significant increase [from 16.3 (95%CI = 11; 21.6) in 1997–1999 to 53.3 (95%CI = 45.9; 60.6) in 2008–2013; P < 0.001]. The mortality rate of PE-related hospitalizations showed a similar trend as PE incidence. In conclusion, the epidemiological trends of PE in PLWH changed during the cART era, with decreases in incidence and mortality in HIV-monoinfected and increases in both variables in patients coinfected with HIV/HCV.

• direct-acting antivirals
• hepatitis C virus
• insulin resistance
• liver fibrosis

• HIV/HCV coinfection
• hepatitis C virus treatment
• mortality

• Antiretroviral therapy
• Direct-acting antivirals
• Drug-drug interactions
• HIV-HCV Coinfection
• Sustained virologic response

• Adult
• Aged
• Antiviral Agents/adverse effects
• Antiviral Agents/therapeutic use
• Coinfection/complications
• Coinfection/drug therapy
• Drug Interactions
• Drug Therapy, Combination/adverse effects
• Female
• HIV Infections/complications
• HIV Infections/drug therapy
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Humans
• Male
• Middle Aged
• Treatment Outcome

Direct acting antivirals (DAAs) have revolutionized hepatitis C (HCV) treatment with >90% cure rates even in real‐world studies, giving hope that HCV can be eliminated. However, for DAAs to have a population‐level impact on the burden of HCV disease, treatment uptake needs to be expanded. We investigated temporal trends in HCV treatment uptake and evaluated factors associated with second‐generation DAA initiation and efficacy among key HIV‐HCV co‐infected populations in Canada.

The Canadian HIV‐HCV Co‐Infection Cohort Study prospectively follows 1699 participants from 18 centres. Among HCV RNA+ participants, we determined the incidence of HCV treatment initiation per year overall and by key populations between 2007 and 2015. Key populations were based on World Health Organization (WHO) guidelines including: people who actively inject drugs (PWID) (reporting injection drug use, last 6 months); Indigenous people; women and men who have sex with men (MSM). Multivariate Cox models were used to estimate adjusted hazard ratios (aHR) and 2‐year probability of initiating second‐generation DAAs for each of the key populations.

Overall, HCV treatment initiation rates increased from 8 (95% CI, 6–11) /100 person‐years in 2013 to 28 (95% CI, 23–33) /100 person‐years in 2015. Among 911 HCV RNA + participants, there were 202 second‐generation DAA initiations (93% with interferon‐free regimens). After adjustment (aHR, 95% CI), active PWID (0.60, 0.38–0.94 compared to people not injecting drugs) and more generally, people with lower income (<$18 000 CAD/year) (0.50, 0.35, 0.71) were less likely to initiate treatment. Conversely, MSM were more likely to initiate 1.95 (1.33, 2.86) compared to heterosexual men. In our cohort, the population profile with the lowest 2‐year probability of initiating DAAs was Indigenous, women who inject drugs (5%, 95% CI 3–8%). Not having any of these risk factors resulted in a 35% (95% CI 32–38%) probability of initiating DAA treatment. Sustained virologic response (SVR) rates were >82% in all key populations.

While treatment uptake has increased with the availability of second‐generation DAAs, marginalized populations, already engaged in care, are still failing to access treatment. Targeted strategies to address barriers are needed to avoid further health inequities and to maximize the public health impact of DAAs.

• Direct acting antivirals (DAAs)
• Disparities
• HIV-hepatitis C co-infection
• Indigenous peoples
• Men who have sex with men (MSM)
• People who inject drug (PWID)
• Women

• AIDS
• Cardiovascular disease
• Deep venous thrombosis
• Hepatitis C
• ICD9CM codes
• Incidence

• Adult
• Coinfection/complications
• Female
• HIV Infections/complications
• HIV Infections/epidemiology
• Hepatitis C/complications
• Hospitalization/statistics & numerical data
• Humans
• Incidence
• Logistic Models
• Male
• Retrospective Studies
• Risk Factors
• Spain/epidemiology
• Venous Thrombosis/epidemiology
• Venous Thrombosis/etiology

The treatment of hepatitis C virus (HCV) in HCV/human immunodeficiency virus (HIV) co-infected patients remains complex. This present meta-analysis evaluated the efficacy and safety of Sofosbuvir (SOF) for treatment in HCV/HIV co-infected patients using the most recent and available data.

A systematic search of the published data was conducted in PubMed Medline, EMBASE and Cochrane databases. Eligible studies were clinical trials, case-control studies or prospective cohort studies aiming at assessing the efficacy and safety of the SOF-containing regimens in patients co-infected with HCV and HIV. Heterogeneity of results was assessed and a pooled analysis was performed using random effects model with maximum likelihood estimate and 95% confidence intervals (95%CI). Subgroup analysis and assessment of publication bias through Egger’s test were also performed. STATA 13.0 software was used to analyze the data.

Seven studies (n = 1167 co-infected patients) were included in this analysis. The pooled estimate of sustained virological response at 12 weeks (SVR12) was 94.0% (95%CI: 92.0%–95.0%). Subgroup analysis showed that the treatment-naïve patients had higher SVR12 compared with patients that were treated before (χ² = 21.39, P < 0.01). The pooled incidence of any adverse events (AEs) was 79.6% (95%CI: 77.1%–82.1%). Publication bias did not exist.

The results of this study showed that the treatment response of SOF-containing regimens in patients co-infected with HIV and HCV was satisfied. Attention should be paid to the high rates of AEs.

The online version of this article (10.1186/s12985-018-0934-6) contains supplementary material, which is available to authorized users.

• HCV/HIV co-infection
• Meta-analysis
• SVR12
• Sofosbuvir

• Doppler
• abdominal
• acoustic radiation force impulse
• hepatobiliary
• liver fibrosis
• transient elastography

• Coinfection/complications
• Coinfection/diagnostic imaging
• Elasticity Imaging Techniques/methods
• Female
• HIV Infections/complications
• HIV Infections/diagnostic imaging
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/diagnostic imaging
• Humans
• Liver/diagnostic imaging
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnostic imaging
• Male
• Middle Aged
• Severity of Illness Index

• 2-Naphthylamine
• Amides
• Aminoisobutyric Acids
• Anilides/therapeutic use
• Antiviral Agents/therapeutic use
• Benzimidazoles/therapeutic use
• Benzofurans/therapeutic use
• Carbamates/therapeutic use
• Cyclopropanes
• Disease Management
• Drug Therapy, Combination
• Hepacivirus/drug effects
• Hepacivirus/pathogenicity
• Hepacivirus/physiology
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/drug therapy
• Hepatitis C, Chronic/physiopathology
• Humans
• Imidazoles/therapeutic use
• Lactams, Macrocyclic
• Leucine/analogs & derivatives
• Macrocyclic Compounds/therapeutic use
• Practice Guidelines as Topic
• Proline/analogs & derivatives
• Pyrrolidines
• Quinoxalines/therapeutic use
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/drug therapy
• Renal Insufficiency, Chronic/physiopathology
• Risk Factors
• Ritonavir/therapeutic use
• Sulfonamides/therapeutic use
• Uracil/analogs & derivatives
• Uracil/therapeutic use
• Valine

• Atherosclerosis
• Cardiovascular disease
• Cerebrovascular disease
• Coronary heart disease
• Hepatitis C

• Co-infection avec une hépatite virale
• HIV
• Hospitalisation
• Hospitalization
• Morbidité sévère
• Severe morbidity
• VIH
• Viral hepatitis coinfection

• Dasabuvir
• Extrahepatic manifestations
• Glucose
• Hepatitis c
• Ombitasvir
• Paritaprevir
• Placebo
• Ritonavir
• Triglycerides
• eGFR

• AbbVie

• Hepatitis C virus. Dialysis. Chronic kidney disease. Direct-acting antiviral agents

To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic.

A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy.

Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn’t reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%).

This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART. Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

• Hepatitis C
• Human immunodeficiency virus
• Ledipasvir
• Sofosbuvir

• cirrhosis
• fibrosis progression
• human immunodeficiency virus/hepatitis C virus coinfection
• interferon
• spontaneous clearance
• sustained virological response