HIV/hepatitis C Virus Genotype Research Articles

The British HIV Association national clinical audit 2021: Management of HIV and hepatitis C coinfection.

We aimed to describe clinical policies for the management of people with HIV/hepatitis C virus (HCV) coinfection and to audit routine monitoring and assessment of people with HIV/HCV coinfection attending UK HIV care. This was a clinic survey and retrospective case-note review. HIV clinics in the UK participated in the audit from May to July 2021 by completing an online questionnaire regarding their clinic's policies for the management of people with HIV/HCV coinfection, and by contributing to a case-note review of people living with HIV with detectable HCV RNA who were under the care of their service. Ninety-five clinics participated in the clinic survey; of these, 15 (15.8%) were regional specialist centres, 19 (20.0%) were HIV services with their own coinfection clinics, 40 (42.1%) were HIV services that referred coinfected individuals to a local hepatology service and 20 (21.1%) were HIV services that referred to a regional specialist centre. Eighty-one clinics provided full caseload estimates; of the approximately 3951 people with a history of HIV/HCV coinfection accessing their clinics, only 4.9% were believed to have detectable HCV RNA, 3.15% of whom were already receiving or approved for direct-acting antiviral (DAA) treatment. In total, 29 (30.5%) of the clinics reported an impact of COVID-19 on coinfection care, including delays or reductions in the frequency of services, monitoring, treatment initiation and appointments, and changes to the way that treatment was dispensed. Case-note reviews were provided for 283 people with detectable HCV RNA from 74 clinics (median age 42 years, 74.6% male, 56.2% HCV genotype 1, 22.3% HCV genotype 3). Overall, 56% had not received treatment for HCV, primarily due to lack of engagement in care (54.7%) and/or being uncontactable (16.4%). Our findings show that the small number of people with HIV with detectable HCV RNA in the UK should mean that it is possible to achieve HCV micro-elimination. However, more work is needed to improve engagement in care for those who are untreated for HCV.

Trends in hepatitis C treatment initiation among HIV/hepatitis C virus-coinfected men engaged in primary care in a multisite community health centre in Maryland: a retrospective cohort study

ObjectivesLittle is known about the cascade of hepatitis C care among HIV/hepatitis C virus (HCV)-coinfected patients in community-based clinics. Thus, we analysed our data from the interferon era to understand...

Interferon-free therapy for treating hepatitis C virus in difficult-to-treat HIV-coinfected patients.

Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95-4.1; P ≤ 0.0001). This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.

A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection.

BackgroundLiver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis.MethodsA case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible. Pro-fibrogenic markers and Interferon Lambda (IFNL) rs8099917 genotype were measured from first available sample in all fibrosis cases (APRI ≥ 1.5 during follow-up) and the subcohort. We used Cox proportional hazards and compared Model 1 (selected clinical predictors only) to Model 2 (Model 1 plus selected markers) for predicting 3-year risk of liver fibrosis using weighted Harrell’s C and Net Reclassification Improvement indices.Results113 individuals developed significant liver fibrosis over 1300 person-years (8.63 per 100 person-years 95% CI: 7.08, 10.60). Model 1 (age, sex, current alcohol use, HIV RNA, baseline APRI, HCV genotype) was nested in model 2, which also included IFNL genotype and IL-8, sICAM-1, RANTES, hsCRP, and sCD14. The C indexes (95% CI) for model 1 vs. model 2 were 0.720 (0.649, 0.791) and 0.756 (0.688, 0.825), respectively. Model 2 classified risk more appropriately (overall net reclassification improvement, p<0.05).ConclusionsIncluding IFNL genotype and inflammatory markers IL-8, sICAM-1, RANTES, hs-CRP, and sCD14 enabled better prediction of the 3-year risk of significant liver fibrosis over clinical predictors alone. Whether this modest improvement in prediction justifies their additional cost requires further cost-benefit analyses.

Coinfection with HIV and hepatitis C virus in 229 children and young adults living in Europe.

To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment. Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts. Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol. Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4 cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV. The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.

High frequency of potential interactions between direct-acting antivirals and concomitant therapy in HIV/hepatitis C virus-coinfected patients in clinical practice.

The aim of the study was to analyse the frequency and degree of potential drug-drug interactions (DDIs) between direct-acting antivirals (DAAs) and concomitant medication used by HIV/hepatitis C virus (HCV)-coinfected patients, including antiretroviral therapy (ART) and other drugs. All patients with HIV infection and viraemic HCV genotype 1, 3 or 4 coinfection attending a tertiary care centre in Spain (November 2014 to November 2015) were included in the study. DDIs were classified as major, i.e. drugs should not be co-administered, or minor, i.e. close monitoring, dosage alteration or change in timing may be required if drugs are co-administered, following the http://www.hep-druginteractions.org database recommendations. A total of 244 patients were included in the study, of whom 224 (92%) were previous injecting drug users. Major DDIs were found for: paritaprevir-r/ombitasvir plus dasabuvir (3D), in 60 (44%) of 138 individuals with genotype 1; paritaprevir-r/ombitasvir (2D), in 22 (37%) of 60 individuals with genotype 4; sofosbuvir/ledipasvir (SOF/LDV), in four (2%) of 198 patients with genotype 1 or 4; simeprevir (SMV) plus SOF, in 160 (81%) of 198 patients with genotype 1 or 4; daclatasvir (DCV) plus SOF, in seven (3%) of 244 patients with genotype 1, 3 or 4 (P < 0.001). Minor DDIs were found for: 3D, in 123 (89%) individuals with genotype 1; 2D, in 52 (87%) individuals with genotype 4; SOF/LDV, in 154 (78%) patients with genotype 1 or 4; SMV plus SOF, in 129 (65%) patients with genotype 1 or 4; DCV plus SOF, in 149 (61%) patients with genotype 1, 3 or 4 (P < 0.001). Drug-drug interactions between DAAs and ART or other commonly prescribed medications are frequently found among HIV/HCV-coinfected patients. Potential major and minor DDIs are more frequent with 3D, 2D and SMV plus SOF regimens.

Impact of PNPLA3 variants on liver histology of 168 patients with HIV infection and chronic hepatitis C

This study analysed the impact of PNPLA3 variants on liver histology of 168 HIV/hepatitis C virus (HCV)-coinfected patients who were naïve for HCV treatment. A athologist unaware of the patients' condition graded liver fibrosis and necroinflammation (Ishak) and steatosis (Kleiner). Patients were tested for PNPLA3 variants and genotyped for the PNPLA3 rs738409 C to G variant underlying the I148M substitution. All were hepatitis B surface antigen negative and stated no alcohol abuse. The mean age was 40.6 (37.6–44.1) years, 72.6% were males, 42% had HCV genotype 3, 38.9% HCV genotype 1 and 79.2% were receiving highly active antiretroviral therapy. The 79 patients with the PNPLA3 p.148I/M or M/M variants more frequently showed severe steatosis (score 3–4) than the 89 with PNPLA3 p.148I/I (43% vs. 24.7%, p 0.001), whereas no difference was observed in the degree of necroinflammation or fibrosis. Compared with 112 patients with lower scores, 56 with severe steatosis showed higher body mass index (p 0.03), higher rate of HCV genotype 3 (55.6% vs. 35.2%, p 0.01), PNPLA3 p.148I/M or M/M (60.7% vs. 39.3%, p 0.01) and lower CD4+ cells/mm3 (514.00 (390.5–673.0) vs. 500.00 (399.0–627.0); p 0.002). At multivariate analysis, body mass index (p 0.01), HCV genotype 3 (p 0.006), CD4+ cell count (p 0.005) and PNPLA3 p.148I/M or M/M variants (p 0.01) were found to be independent predictors of severe liver steatosis. The PNPLA3 p.148 I/M or M/M variants and CD4+ cell count were the only independent predictors of severe steatosis in patients with HCV non-3 genotypes. This is the first study to show that among HIV/HCV-coinfected patients the PNPLA3 p.148I/M or M/M variant have substantially less impact on steatosis for those with HCV genotype 3 than non–genotype 3.

Effects of sustained viral response in patients with HIV and chronic hepatitis C and nonadvanced liver fibrosis.

We assessed the effects of sustained viral response (SVR), after treating with interferon-ribavirin (IF-RB), on mortality, liver-related (LR) events (decompensation, hepatocellular carcinoma), HIV progression, and liver stiffness in HIV/hepatitis C virus (HCV)-coinfected patients with nonadvanced liver fibrosis. From a cohort of HIV/HCV-coinfected patients treated with IF-RB, we selected those with baseline liver fibrosis stages F0, F1, or F2 according to METAVIR. The study started when IF-RB was stopped and ended at death or at the last follow-up visit. A total of 695 patients were included (HCV genotype 1 or 4, 431; F0, 77; F1, 290; and F2, 328), and 274 patients achieved SVR. After a median follow-up of 4.9 years, the adjusted hazard ratio (aHR) [95% confidence interval (CI)] of LR events or overall death, for patients with SVR taking the group of patients with no SVR as a reference was 0.217 (0.079 to 0.599) (P = 0.003) for the whole cohort with F0 to F2. For patients with F0, the aHR (95% CI) was 0.514 (0.040 to 6.593) (P = 0.609), for patients with F1, the aHR (95% CI) was 0.305 (0.053 to 1.762) (P = 0.185), and for patients with F2, it was 0.075 (0.009 to 0.662) (P = 0.020). We also found that, in comparison with no SVR, SVR was followed by less frequent HIV progression for the entire population (F0 to F2) and less frequent liver stiffness across all categories of fibrosis. SVR in HIV/HCV-coinfected patients with moderate stages of liver fibrosis is associated with a reduction of mortality and LR events, and with a reduction of progression of HIV and liver fibrosis.

European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV‐coinfected patients

Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV). We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data. The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype. European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.

Prediction of Hepatic Fibrosis in Patients Coinfected With HIV and Hepatitis C Virus Based on Genetic Markers

To assess the ability of the cirrhosis risk score (CRS) to predict liver fibrosis progression in HIV/hepatitis C virus (HCV)-coinfected patients. Retrospective follow-up study. Based on a minimum follow-up time of 10 years with HCV infection, 190 HIV/HCV-coinfected patients were classified according to their METAVIR score: (1) 25 nonprogressor patients who did not develop fibrosis (F0) and (2) 165 progressor patients who developed fibrosis (F ≥ 1). Seven polymorphisms of CRS signature and IL28B genotype were performed using the GoldenGate assay. The CRS signature was calculated by naive Bayes formula as previously described. Nonprogressors had CRS values significantly lower than progressors (0.61 versus 0.67; P = 0.043). Among the progressors, we observed similar CRS values through all the fibrosis stages (F1/F2/F3/F4). The percentage of patients with CRS > 0.70 (high risk of developing fibrosis) was higher in progressors than in nonprogressors; but the percentages with values between 0.50 and 0.70 (intermediate risk) and <0.50 (low risk) were quite similar for each of the fibrosis stages (P = 0.047). The area under the receiver-operating characteristic curve of CRS for discriminating nonprogressor versus progressor was 0.625 (P = 0.043). When clinical variables were considered (age at HCV infection, intravenous drug use, gender, IL28B, and HCV genotype), the area under the receiver-operating characteristic curve of CRS improved up to 0.739 (P < 0.001). CRS itself seems not to be a good marker for identifying HIV/HCV-coinfected patients who are at high risk of developing liver fibrosis. However, CRS score coupled with clinical factors might help to distinguish between nonprogressors and progressors patients.

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

To identify genetic factors that predict sustained virological response (SVR) to pegylated interferon (Peg-IFN)/ribavirin (RBV) in HIV/hepatitis C virus (HCV) genotype 1 or 4-coinfected patients and that enhance the predictive capacity of IL28B genotype in this population. Prospective cohort study. Five tertiary care centers in Spain. Two hundred and five HIV/HCV genotype 1 or 4-coinfected patients who received a complete course of Peg-IFN/RBV for 48 weeks. All individuals were genotyped for 144 single-nucleotide polymorphisms (SNPs). One hundred and sixty-two (79%) patients bore HCV genotype 1. Overall SVR was achieved by 73 (36%) individuals. SNPs at the following genes were associated with SVR: IL28B, low-density lipoprotein receptor (LDLR), transforming growth factor β (TGF-β), aquaporine 2 (AQP-2), very-low-density lipoprotein receptor, Sp110 nuclear body protein, interferon alpha/beta receptor 1, 2'-5'-oligoadenylate synthase 1 and apolipoprotein B. There was a strong synergy between SNPs at IL28B, TGF-β and AQP-2 genes: the number of patients reaching SVR with all three favorable genotypes versus unfavorable genotypes were 22 (78.6%) versus 1 (7.1%) (P = 2.1 × 10). HCV baseline viral load, IL28B, TGF-β, AQP-2 and LDLR haplotypes were independently associated with SVR. A number of genetic factors modify the predictive capacity of IL28B genotype. These can be used to identify HCV genotype 1 or 4-infected patients with a very high or a very low probability to respond to bitherapy with Peg-IFN/RBV. Predictive models based on these factors could be helpful to tailor direct acting antiviral-based therapy.

Epidemiological distribution and genotype characterization of hepatitis C virus and HIV co-infection in Wuhan, China, where the prevalence of HIV is low

Little is known about the epidemiological characteristics of HIV/hepatitis C virus (HCV) co-infection in cities in China with low HIV prevalence. This study evaluated the level of exposure to different risk factors associated with HCV transmission and characterized the distribution of HCV genotypes in 356 HIV-1-positive patients in Wuhan, central China. HIV transmission routes were distributed as follows: heterosexual contact, male-to-male sexual contact, intravenous drug use, blood transfusion, and unknown route. HCV antibodies were detected by a third-generation enzyme-linked immunosorbent assay. HCV-positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. Phylogenetic analysis characterized HCV subtypes and the evolutionary origin of circulating HCV strains. Ninety-two of 356 (25.8%) patients infected with HIV were anti-HCV-positive. Among co-infected patients, the predominant risk for HCV transmission was intravenous drug use (87.3%). Six HCV subtypes (1a, 1b, 2a, 3a, 3b, and 6a) were detected. HCV genotype 6a was most prevalent, occurring in 39.3% of all patients, followed by genotypes 1b (24.7%), 3b (18.0%), and 3a (9.8%). The least frequent genotypes were 1a (4.9%) and 2a (3.3%). Intravenous drug use was strongly associated with genotype 6a, and infection by blood or blood product transfusion was strongly associated with genotype 1b. Genotype 2a was detected only among those infected by male-to-male sexual contact. The distribution of HCV subtypes suggests that the city plays a crucial role as a hub of HCV transmission in China. Exposure to multiple risk factors associated with HCV transmission was common among patients co-infected with HIV and HCV.

HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy

To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients. Retrospective follow-up study. We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment. The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35-3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03-2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47-31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ± 0.024. The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.

IL28B Polymorphism, Pretreatment CXCL10, and HCV RNA Levels Predict Treatment Response in Racially Diverse HIV/HCV Coinfected and HCV Monoinfected Patients

We sought to develop a score to predict sustained virological response (SVR) in racially diverse HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected pegylated interferon/ribavirin-treated patients. We retrospectively evaluated 374 patients (259 monoinfected and 115 coinfected) treated at a single tertiary care center. The IL28B rs12979860 single nucleotide polymorphism genotyping was performed in 335 patients, and plasma CXCL10 levels were measured by enzyme-linked immunosorbent assay in 171 patients. Of the 374 patients, 64.9% were white, 17.2% were African American, 76.5% were HCV genotype 1 infected, and 49.3% had advanced fibrosis. Sustained virological response was achieved by 151 (40.4%) patients, 106 (40.9%) patients monoinfected, and 45 (39.1%) patients coinfected. Patients with IL28B C/C genotype were significantly more likely to achieve an SVR compared with non-C/C genotype patients, but only if they were infected with HCV genotypes 1/4 (59.1% vs 21.1%, P < 0.0001). No significant differences existed in IL28B predictive capacity between coinfected and monoinfected patients. Pretreatment CXCL10 levels were significantly higher in nonresponders, both monoinfected and coinfected, compared with SVR patients (P = 0.0018). Coinfected patients had higher CXCL10 levels compared with monoinfected patients (P = 0.03). The combination of IL28B genotype, pretreatment CXCL10 and HCV RNA levels, and HCV genotype had the best ability to predict treatment response in both patient groups (area under the receiver operating characteristic curve = 0.85). Among all patients, a cutoff score of -0.94 or more had a sensitivity of 0.93 and specificity of 0.59. In coinfected patients, a score of -0.55 or more had sensitivity of 0.81 and specificity of 0.80. IL28B genotype, pretreatment CXCL10, and HCV RNA levels have very good capacity to predict pegylated interferon/ribavirin-treatment outcome in both HIV/HCV coinfected and HCV monoinfected patients.

Optimizing Hepatitis C Therapy in HIV/hepatitis C Virus (HCV) Coinfected Patients: Analysis of HCV Viral Kinetics on Treatment

Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy. Hepatitis C virus (HCV) infection is potentially curable, but the sustained virological response (SVR) has been shown to be lower in patients coinfected HIV. A single-centre experience treating individuals with HCV and HIV coinfection is reported. Twenty-one patients who received standard doses of pegylated interferon with weight-based dosing of ribavirin (mean 14.3 mg/kg) were retrospectively reviewed. Qualitative HCV polymerase chain reaction (PCR) was performed prospectively every four weeks if the patient remained HCV PCR positive. All patients with HCV genotype 1 were treated for 48 weeks. Patients with genotype 2 or 3 were treated for 24 weeks and 32 weeks to 36 weeks if their HCV RNA level was undetectable after four weeks (RVR4) or eight weeks (RVR8) of therapy, respectively. If RVR8 was not achieved, the treatment was continued for 48 weeks. There were no dropouts or dose reductions within the first 12 weeks of treatment. SVR status was available for 20 patients and adequate serum for viral kinetics analyses was available for 17 patients. Eighty per cent of the patients achieved SVR (50% genotype 1; 100% genotypes 2 and 3). The week 8 viral load remained elevated for all genotype 1 nonresponders. High effectiveness rates were seen, particularly in patients with HCV genotype 2 and 3 who were treated for shorter durations. HCV viral loads after eight weeks of therapy helped distinguish patients with HCV genotype 1 who would respond to therapy.

High Frequency of Advanced Hepatic Disease among HIV/HCV Co-Infected Patients in Cambodia: The HEPACAM Study

Background: Little is known about HIV/Hepatitis C Virus (HCV) co-infection in resource-limited countries, although chronic HCV infection is one of the most relevant comorbidities in HIV population. The aim of this study was to determine the severity of liver disease in a cohort of HIV/HCV co-infected patients followed in Calmette Hospital, Phnom Penh, Cambodia, and to analyse the impact of HCV infection on antiretroviral therapy efficacy and hepatotoxicity. Methods: HIV patients with positive HCV antibodies were enrolled in this cross-sectional study. HIV monoinfected patients formed the control group. Transverse evaluation of co-infected patients was performed collecting clinical, biological, virological and ultrasonographic data. HIV course, response to antiretroviral therapy and frequency of hepatocytolysis were compared in both groups. Results: Among 50 HIV patients known with HCV antibodies, 31 (62%) had positive plasma HCV RNA and were included (58% men, median age 44 years). HCV genotype 1 was the most prevalent (68%), followed by genotype 6 (25%). Twelve patients (39%) met clinical, biological and/or ultrasonographic criteria for cirrhosis. FibroTest stage was 3-4 in 16 patients (52%). HIV/HCV co-infected patients demonstrated similar immune restoration and virological response to antiretroviral therapy as the 160 HIV mono-infected patients. Co-infected patients were more likely to have alanine aminotransferase elevation at baseline and to develop grade 2 or 3 hepatocytolysis in the two years after antiretroviral therapy initiation, specifically when nevirapine was used during the first six months of treatment. Conclusions: HIV/HCV co-infected patients are at increased risk for acquiring severe hepatic fibrosis. HCV coinfection does not affect response to ART. Efavirenz should be preferred to nevirapine in co-infected patients due to hepatotoxicity. Further research is required to target access to appropriate management of HIV/HCV co-infections in resource-limited countries.

Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNA load

This study aimed at developing a predictive algorithm based on interleukin 28B (IL28B) genotype, hepatitis C virus (HCV) genotype, and plasma HCV-RNA load, which could accurately allow us to define the probability of response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in HIV/HCV-coinfected patients. Five hundred and twenty-one treatment-naive HIV-infected patients, who initiated HCV therapy with Peg-IFN/RBV, were analysed in an on-treatment basis. Patients were categorized as unlikely responders, uncertain responders, and anticipated responders (<20%, 20-60%, and >60% probability to achieve SVR, respectively). HCV genotype, baseline HCV-RNA load, and IL28B genotype were confirmed as independent predictors of SVR in a logistic regression analysis. A stepwise algorithm based on these three variables was created based on 321 patients and evaluated in the remaining 200 patients. Unlikely responders included patients with genotype 1 or 4, HCV-RNA load ≥600,000IU/ml, and rs12979860 non-CC (rate of SVR: 17.3%). Anticipated responders were those with HCV genotype 2-3, patients harboring HCV genotype 4 and IL28B CC, as well as those who simultaneously bore HCV genotype 1, HCV-RNA load <600,000IU/ml, and IL28B CC (rate of SVR 74.1%, 77.8%, and 64.4%, respectively). The area under the receiver operating characteristic curve of the model was 0.77 (0.733-0.814). The combined use of IL28B genotype, HCV genotype, and HCV-RNA load enables to easily identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients, until more effective options are available, at least if they do not show advanced liver fibrosis.

Liver transplant outcomes in HIV-infected patients

We read with interest the article entitled ‘Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with a synthetic cohort’ by Cooper et al.[1]. This article is very interesting because it describes systematically 15 cohort studies and 49 case series with individual patient data. It is now generally accepted that liver transplantation in HIV-infected patients is feasible; in HIV/hepatitis C virus (HCV) co-infected patients, we and others have demonstrated that survival at 1 year after liver transplantation ranges from 58% to 89% [2,3]; when we compared these rates with a series of mono-infected patients, survival was lower in the co-infected group, the 2-year and 5-year patient survival rates being 73% vs. 91% and 51% vs. 81%, respectively, (P = 0.004). Moreover, concerning HIV/hepatitis B virus (HBV) co-infected patients, survival was excellent, the rate reaching 100% survival at 5 years [4]. In the study by Cooper et al. [1], some points need to be detailed or explained and discussed. The constitution of a synthetic cohort from grouped case data is an original and interesting method. However, the character of ‘grouped cases’ with a lack of details concerning the indications of liver transplantation (hepatocellular carcinoma or end-stage liver cirrhosis) and virologcial characteristics (HCV viral load at the time of liver transplantation, HCV genotype) is a concern. More generally, provision of such information is particularly important for overcoming the problem of patient heterogeneity. Concerning HIV/HCV co-infected patients, the authors considered that HCV was a negative predictor of patient survival in the unadjusted model [0.23, 95% confidence interval (CI) 0.07–0.79],l but not when it was adjusted by other key predictors of patient survival (0.54, 95% CI 0.17–1.80). This result is surprising; the authors need to provide details on which other predictor factors they used. The authors found that a Model End-Stage Liver Disease (MELD) score of at least 14 is a prognostic factor for survival in nonadjusted analyses. Interpretation of this cut-off point is difficult because it pools different subgroups of patients, such as those with hepatocellular carcinoma and a low MELD score and those with complicated cirrhosis with a high MELD score. In our cohort of HIV/HCV co-infected patients, we demonstrated that the MELD score as a continuous variable was an independent factor for survival under multivariate analysis [2]. The authors found a significant difference in survival as a function of the year of publication (</>2001). This point is interesting; we agree that modifications to antiretroviral regimens may influence postliver transplantation survival [5]; other important factors such as registration on the waiting list of patients with less severe liver disease, or a more systematic introduction of anti-HCV therapy after liver transplantation, also need to be mentioned. The authors found a percentage of fibrosing cholestatic hepatitis of 12% at 5 years after liver transplantation. This very severe complication has been reported in 5% HBV or HCV mono-infected patients. We recently demonstrated that this type of complication occurred in 11 (19%) of 59 HIV/HCV co-infected patients transplanted for end-stage liver disease. Clearly, it is necessary to prevent this high recurrence rate through the early detection of predictive factors and the early initiation of anti-HCV therapy [6]. In conclusion, this study is important because it demonstrates that survival after liver transplantation in HIV-infected patients is similar to that of HIV-negative patients. However, other large studies are needed to individualize prognosis factors after liver transplantation in a well characterized subgroup of HIV-infected patients. Acknowledgements Conflicts of interest None declared.

Impact of IL28B polymorphisms on response to peginterferon and ribavirin in HIV–hepatitis C virus-coinfected patients with prior nonresponse or relapse

IL28B polymorphisms predict treatment response in chronic hepatitis C. However, no information exists in prior treatment failures. A total of 62 HIV/hepatitis C virus (HCV) patients who completed retreatment with peginterferon-α/ribavirin were examined, of whom 25 (40%) had been cured. Predictors of response [odds ratio, OR (95% confidence interval, CI)] were HCV genotypes 2/3 [16.1 (2.7-90.9)], prior relapse [9.6 (1.5-62.4)] and ribavirin plasma trough concentrations at week 4 [4.9 (1.3-18.4)]. IL28B-CC only predicted response in prior nonresponders carrying HCV genotypes 1/4 [25.1 (1.9-337)].

Insulin Resistance Impairs Response to Interferon Plus Ribavirin in Patients Coinfected With HIV and Hepatitis C Virus

Controversy exists about whether insulin resistance (IR) affects response to treatment of hepatitis C. We evaluated the effect of IR on sustained virologic response (SVR) in HIV/hepatitis C virus (HCV)-coinfected patients treated with interferon plus ribavirin. We reviewed the clinical records of HIV/HCV-coinfected patients who received interferon plus ribavirin at our institution between July 2000 and March 2007. IR was defined as a homeostasis model assessment ≥ 3.8. SVR was defined as an undetectable HCV RNA at 24 weeks after the end of treatment. Efficacy was evaluated using an on-treatment (OT) analysis. Multivariate logistic regression analysis was used to evaluate factors associated with SVR. During the study period, 218 patients were treated with interferon plus ribavirin; IR at baseline was available for 162 patients, and 134 were included in the OT analysis; HCV genotype (G) 1/4, 67%; F3-F4 fibrosis, 36%; IR 31%. SVR was achieved in 67 patients (50%) (79% in G 2/3 vs. 38% in G 1/4). IR was associated with a lower SVR [odds ratio (OR), 0.33; 95% confidence interval (CI): 0.15-0.72; P = 0.006). The independent variables related to SVR were genotype 2/3 (OR, 6.7; 95% CI: 2.71-16.98; P < 0.001), absence of IR at baseline (OR, 3.3; 95% CI: 1.36-8.26; P = 0.008), and nadir CD4 T-cell count (OR, 1.002; 95% CI: 1.00-1.00; P = 0.047). Our data suggest that IR is an important determinant of SVR in HIV/HCV-coinfected patients treated with interferon plus ribavirin. Strategies to modify IR should be explored to enhance SVR during anti-HCV therapy.