HIV-HCV Co-infected Patients Research Articles

Study of miR-29a-5p Expression in HIV Positive and HIV/HCV Co-Infected Patients in Sanandaj-Iran

Background: Co-infection of human immunodeficiency virus (HIV) with hepatitis virus accelerates liver injury. Recently, there has been paid more attention to micro RNAs (miRs) as new tools for determination of liver injury. Previous studies revealed that miR-29 inhibits HIV replication. It has been also shown that miR-29 decreases in hepatocytes of hepatitis C virus (HCV) infected patients. The present study aimed to determine the miR-29a-5p expression as a possible diagnostic marker in HIV- and HIV-HCV co-infected patients. Methods: In this cross-sectional study, blood samples were collected from 40 healthy, 44 HIV-positive, and 121 HIV/HCV co-infected subjects. Blood CD4+ (cluster of differentiation 4) cell counts were recorded and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, miR-29a-5p expression, fibrosis-4 (FIB-4), and AST to platelet ratio index (APRI) index were determined. Data were analyzed by SPSS version 16 and p value less than 0.05 was considered statistically significant. Results: Serum ALT and AST activities and FIB-4 and APRI were significantly higher in HIV-HCV-co-infection group than the control group (P< 0.05); however, miR-29a-5p was down-regulated in patients compared to controls. CD4+ cell counts markedly decreased in all patients and showed a significant direct correlation with miR-29a-5p (rs = 0.225, P < 0.045). The inverse significant correlation of FIB4 and APRI with miR-29a-5p expression was also seen (rs = -0.691, P = 0.005 and rs = -0.712, p<0.001, respectively). Conclusions: miR-29a-5p was significantly down-regulated in HIV- and HIV/HCV-co-infected patients and showed a correlation with liver injury. Down-regulation of miR-29a-5p was directly associated with CD4+ cell counts and reversely correlated with FIB-4 and APRI index. Therefore, the determination of miR-29a-5p may be useful, among other markers, for diagnosis of these diseases.

FREQUENCY OF THE MDR1 GENE POLYMORPHISM RS1045642 (C3435T) IN HCV-HIV CO-INFECTED PATIENTS.

Due to the high prevalence of co-infection by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and the severity of these infections, the understanding of the biological mechanisms involved in these processes, including viral behavior and host genetic profile, is of great importance for patient treatment and for public health policies.Some single nucleotide polymorphisms (SNPs) in the human genome, such as the SNP rs1045642 (C3435T) in the MDR1 gene, have been reported to be associated to the sustained virological response (SVR) to HCV treatment in HCV-HIV co-infected patients. The present study analyzes the MDR1 gene C3435T polymorphism in HCV-HIV co-infected patients. A total of 99 HCV-HIV patients were included in the study. The DNA was extracted from blood samples, and the SNP rs1045642 was assessed by Real Time PCR (qPCR). Risk factors for acquiring the virus and the SVR after HCV treatment with pegylated interferon-alpha and ribavirin were also analyzed. Among the patients, 54 (54.5%) were male and 45 (45.5%) were female. The average age was 46.1±9.8 years. The SVR after HCV treatment was 40%. The frequencies of MDR1 genotypes CC, CT and TT were 28.3%, 47.5% and 24.2%, respectively. Allele frequencies were 52% for the C allele and 48% for the T allele. No association was found for SNP rs1045642 (C3435T) regarding response to treatment (P=0.308). - In this study, the C3435T polymorphism in the MDR1 gene appears not to be associated with SVR in HCV-HIV co-infected individuals.

Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV–HCV co-infected patients: final results of the Spanish BOC HIV–HCV Study

Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Clinical experience with dolutegravir/abacavir/lamivudine in HIV–HCV co-infected patients treated with a sofosbuvir-based regimen—safety and efficacy

Background: There is no known reason to suspect an adverse drug interaction between dolutegravir-based antiretroviral therapy and sofosbuvir, simeprevir, or ledipasvir. There is a paucity of clinical data for this combination.Methods: Prospective, open-label study of patients with HIV well controlled on dolutegravir, abacavir, and lamivudine, who were co-infected with HCV genotype 1, and required therapy with simeprevir plus sofosbuvir or sofosbuvir/ledipasvir single-tablet regimen (STR) for 12 weeks. The two primary endpoints were percentage of patients achieving sustained virologic response (SVR) at 12 weeks post-treatment and percentage of patients with a HIV-1 viral load <50 copies/ml at end of the combination therapy.Results: Twenty-eight subjects were enrolled from August 2014 to September 2015. Thirteen patients were treated with simprevir plus sofosbuvir, and 15 subjects were treated with sofosbuvir/ledipasvir. 23 genotype 1a, and 5 genotype 1b were included. Nineteen were treatment naïve, and 2 patients had compensated cirrhosis. The mean age was 59 years (95% CI 58.21–59.78 years). The mean age was 59 years (95% CI: 58.21–59.78 years), and 25 patients were black. Out of the 28 patients who completed this study, SVR 12 was achieved in 27 of 28 patients (96%, 95% CI 89.6–100.0%), and all patients had an HIV virus load <50 copies/ml at week 12 of therapy, for an intent-to-treat rate of 100%. No patients ended therapy secondary to adverse events.Conclusion: Our study suggests a good safety and efficacy for the combination of a dolutegravir, abacavir, and lamivudine with sofosbuvir-based DAA therapy.

Occult Hepatitis B in Patients Co-Infected With Hepatitis C and Human Immunodeficiency Viruses

Objectives: Diagnosis of the occult hepatitis B virus (HBV) infection in patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is important due to the fact that the HBV infection may have a clinical impact on liver disease in coinfected HIV/HCV patients. Isolated hepatitis B core antibody (HBcAb) positive HBV infection has been reported in HIV patients. The aim of this study was to determine the occult hepatitis B in patients co-infected with HCV-HIV. Methods: In a cross-sectional study, hepatitis B surface antigen (HBsAg) and HBcAb tests were performed for all HIV-HCV co-infected patients, referred to the HIV Clinic of Hamadan. HBsAb was requested for HBsAg negative-HBcAb positive individuals and in the case of negative HBsAb, HBV-DNA PCR was performed. Finally the collected data was analyzed with SPSS. Results: Of 103 HIV-HCV coinfected patients, both HBsAg and HBcAb were positive in 7 patients (6.8%), negative in 44 (42.7%) patients and 52 (50.5%) of all patients were HBsAg negative and HBcAb positive, which positivity of HBsAg had statistical correlation with positivity of HBcAb. In the last group HBsAb and HBV-DNA PCR were done, which resulted in the titer of antibody to be positive in 4 patients (7.7%) and the PCR to be negative in all (100%) patients. Conclusions: The significant number of coinfected HIV-HCV patients only had HBcAb positive test without detectable HBV-DNA. Further studies for detection of HBV-DNA in both serum and liver biopsy specimens may help clarify the impact of HBV infection in coinfected HIV/HCV patients.

Treatment Outcomes in HCV-HIV Co-infected Patients in an Inner-city Hospital

Treatment Outcomes in HCV-HIV Co-infected Patients in an Inner-city Hospital

Short article: Fatigue in the long term after HCV treatment in HIV–HCV-coinfected patients: functional limitations persist despite viral clearance in patients exposed to peg-interferon/ribavirin-containing regimens (ANRS CO13-HEPAVIH cohort)

To analyze the impact of fatigue on individuals' global, cognitive, physical, and psychosocial functioning in the long term after hepatitis C virus (HCV) treatment and its relationship with HCV clearance among patients coinfected with HIV and HCV exposed to peg-interferon/ribavirin-containing regimens. The study sample included 107 coinfected patients treated for HCV during follow-up in the French ANRS CO13-HEPAVIH cohort. Analyses used scores from the Fatigue Impact Scale (FIS), assessed before treatment initiation and at last available measure after the end of treatment (2 years in median). Patient proportions with a clinically significant improvement in fatigue impact, defined as a decrease higher than 10 points in the 160-point global FIS score, were compared between HCV clearers and chronic HCV patients (Fisher's exact test). Relationships between HCV clearance and FIS scores were analyzed in linear regression models adjusted for sex, time since end of HCV treatment, and pretreatment scores. Twenty-nine percent of patients showed a clinically significant improvement in fatigue (15/57 in HCV clearers vs. 16/50 in chronic HCV patients, P=0.52). HCV clearance was not significantly associated with FIS scores in multivariate models. The role of HCV clearance in coinfected patients' functional recovery in the long term after peg-interferon/ribavirin treatment may be lesser than expected. Additional studies are needed in patients treated with direct-acting antiviral agents. In the meantime, the effectiveness of palliative care and targeted psychological treatments such as cognitive-behavioral therapy in reducing fatigue impact needs to be assessed in the many HCV-cured patients with HIV exposed to suboptimal interferon-based first-generation therapies.

Literature review of the distribution of hepatitis C virus genotypes across Europe.

Recent advances in hepatitis C virus (HCV) therapies have transformed the treatment landscape for this disease. However, efficacy of current treatments depends on HCV genotype and individual patient characteristics. This review aimed to appraise observational studies reporting epidemiological outcomes to characterize HCV genotype distribution in Europe, in the general HCV population and various subpopulations of interest. MEDLINE and EMBASE entries published between November 2008 and November 2013 were systematically searched. Studies were grouped according to the patient populations of interest: general HCV population, HCV-HIV co-infected patients, patients with advanced fibrosis/cirrhosis, and liver transplant recipients. Thirty publications provided estimates of HCV genotype distribution in four distinct patient groups: general HCV population (n = 21), HCV-HIV co-infected patients (n = 6), liver transplant patients (n = 3), and patients with HCV-compensated cirrhosis (n = 1). Nationwide estimates of genotype distribution in the general HCV population were available for 10 countries, with genotypes 1 and 3 the most commonly reported. Romanian studies were found to have reported genotype 1 infections almost exclusively (98.0-99.8%). Considerable regional variation was reported in some countries (e.g., Italy), but not others (e.g., France). National and multi-national estimates for the HCV-HIV co-infected population suggested a different genotype distribution to that in the general HCV population. No studies reported nationwide genotype distribution in patients with advanced liver disease. Given the clinical importance of genotype in developing optimal HCV eradication strategies, further nationwide European studies are needed to fully characterize genotype distribution in both the general HCV population and in HCV subpopulations. J. Med. Virol. 88:2157-2169, 2016. © 2016 Wiley Periodicals, Inc.

Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin.

Effective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV-HCV co-infected patients. This study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV-HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing. DCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA <12 IU/ml at week 12 and undetectable at week 16. Sub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients.

CD4 and CD4/CD8 ratio progression in HIV-HCV infected patients after achievement of SVR

BackgroundIn HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear. ObjectivesThis study aims to determine if CD4 and CD4/CD8 ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR). Study designA total of 116 HIV-HCV co-infected patients, previously treated with Peg-IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 ratio. ResultsMedian HIV-infection duration, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p<0.001) and APRI trend (p<0.001) after SVR was observed in SVR patients compared to those non-SVR. After adjustment for HIV duration, there was no significant difference between the two groups for absolute CD4 (p=0.08) or percentage CD4 slope (p=0.6) over time. The CD4/CD8 ratio trend also demonstrated a similar progressive increase in both groups (p=0.2). During follow-up, six deaths were reported in the non-SVR group versus no death for the SVR group, while no difference in AIDS and non-AIDS events was observed. ConclusionsAchievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 ratio evolution in ART-treated HIV-HCV co-infected patients.

Treatment of severe recurrent hepatitis C after liver transplantation in HIV infected patients using sofosbuvir-based therapy.

For liver transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, recurrence after LT is associated with a higher risk of graft loss than for HCV mono-infected patients. Prior HCV treatment options were limited by side effects and drug-drug interactions. To evaluate treatment outcomes with sofosbuvir (SOF)-based therapy among HIV/HCV coinfected liver transplant recipients. Access to SOF and ribavirin (RBV) prior to regulatory approval was attained via an international compassionate access program for transplant recipients with a life expectancy of 1 year or less in the absence of HCV treatment. This report focuses on the short and longer term outcomes in HCV-HIV co-infected liver transplant recipients. Twenty patients were treated, nine with early severe recurrence and 11 with cirrhosis. Eleven patients received SOF and RBV, one SOF, RBV and Peg-interferon, three SOF, RBV and simeprevir and five SOF, RBV and daclatasvir. Of the 18 patients who completed treatment, 16 (89%) achieved sustained virological response 12 weeks after the end of treatment (SVR12). Liver function tests (including bilirubin and albumin) improved significantly over time. Nineteen serious adverse events occurred in eight (40%) patients, none of them related to SOF. Two patients died during treatment and another, 1 year after the end of therapy, due to progressive end-stage liver disease. Importantly, HIV suppression was not compromised. No significant drug-drug interactions were reported. Sofosbuvir-based regimens are safe, well-tolerated and provide high rates of SVR in HCV-HIV co-infected patients with severe recurrence after-liver transplant.

No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).

Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients' immune systems remains undocumented. Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients. We performed a longitudinal analysis of the relationship between cannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy. Cannabis use was assessed using annual self-administered questionnaires in 955 patients (2386 visits) enrolled in the ANRS CO13-HEPAVIH cohort. The effect of cannabis use on circulating CD4 T-cell count and percentage was estimated using multivariate linear regression models with generalised estimating equations. Sensitivity analyses were conducted after excluding visits where (i) tobacco use and (ii) smoking >=10 tobacco cigarettes/day were reported. At the first visit, 48% of patients reported cannabis use during the previous four weeks, and 58% of these patients also smoked ≥10 tobacco cigarettes/day. After multiple adjustment, cannabis use was not significantly associated with either circulating CD4 T-cell count [model coefficient (95% confidence interval): 0.27 (-0.07; 0.62), P = 0.12] or percentage [-0.04 (-0.45; 0.36), P = 0.83]. Sensitivity analyses confirmed these results. Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients. In-depth immunological studies are needed to document whether cannabis has a harmful effect on CD4 levels in lungs and on cells' functional properties. [Marcellin F, Lions C, Rosenthal E, Roux P, Sogni P, Wittkop L, Protopopescu C, Spire B, Salmon-Ceron D, Dabis F, Carrieri MP, HEPAVIH ANRS CO13 Study Group. No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRSCO13-HEPAVIH French cohort). Drug Alcohol Rev 2017;36:227-238].

Daclatasvir plus sofosbuvir, with or without ribavirin, in real-world patients with HIV-HCV coinfection and advanced liver disease.

HIV-HCV-coinfected patients respond just as well to modern direct-acting antiviral HCV therapy as HCV-monoinfected patients. However, clinical data for all-oral HCV treatments are sparse in HIV-HCV-coinfected patients with an advanced stage of liver cirrhosis. A subanalysis of efficacy and safety for a daclatasvir (DCV) and sofosbuvir (SOF) regimen, with or without ribavirin (RBV), was undertaken in HIV-HCV-coinfected patients with advanced liver disease and no other treatment options enrolled into a European DCV compassionate use programme. Fifty five HIV-HCV (mostly genotypes 1, 3, 4) coinfected patients were treated with DCV+SOF with (n=16) or without RBV (n=39), mostly for 24 weeks. Patients were predominantly (95%) cirrhotic (50% were Child-Pugh class B or C) and were receiving a wide range of antiretrovirals; 40% were injection drug users and 25% were receiving oral opioid substitution. Sustained virological response at post-treatment week 12 (SVR12) by modified intention-to-treat analysis (n=52) was 92% overall (95% CI 81.5, 97.9), and was similar with (94% [95% CI 69.8, 99.8]) or without RBV (92% [95% CI 77.5, 98.2]). Only one patient relapsed (Child-Pugh class B). The overall SVR12 rate after excluding non-virological failures (n=49) was 98% (95% CI 89.1, 99.9). Four patients discontinued treatment for adverse events and one died during treatment (not treatment-related). No patient lost opioid maintenance or required a change of antiretrovirals due to drug-drug interactions. DCV+SOF, with or without RBV, showed high SVR12 rates and was well tolerated in this real-world cohort of HIV-HCV-coinfected patients with very advanced liver disease. ClinicalTrials.gov ID NCT02097966 (Study AI444-237).

Hyperbilirubinaemia in HIV–HCV co-infected patients on antiretroviral therapy: drug effect or liver disease severity?

ObjectiveHyperbilirubinaemia (HB) is common in HIV and hepatitis C virus (HIV–HCV) co-infected patients and poses a unique challenge in management as it may be due to medications such as the...

HCV-HIV co-infected patients: no longer a 'special' population?

Prior to the advent of safe and highly effective hepatitis C virus (HCV) treatment, patients with human immunodeficiency virus (HIV)/HCV co-infection were referred to as a 'special' population. This definition was based on more rapid HCV disease progression in the presence of HIV co-infection, limited effectiveness of interferon-based HCV treatment and potential drug interactions between medications used to treat HIV and those to treat HCV infection. Although the availability of interferon-free, oral direct-acting antivirals (DAAs) has dramatically increased the effectiveness of HCV treatment in patients with HIV co-infection, this population still warrants special consideration. Specific issues for the treatment of patients with HIV/HCV co-infection in the era of oral DAAs include a high HCV disease burden with ongoing HCV infection and re-infection following successful treatment, frequent drug interactions that must be carefully evaluated and unanswered questions on the role of shorter HCV treatment durations.

Elevated Linoleic Acid (A Pro-Inflammatory PUFA) and Liver Injury in a Treatment Naive HIV-HCV Co-Infected Alcohol Dependent Patient.

HIV and HCV co-infection is a unique disease condition, and medical management of such condition is difficult due to severity and systemic complications. Added with heavy alcohol drinking, risk of liver injury increases due to several pro-inflammatory responses that subsequently get involved with alcohol metabolism. Elevated levels of fatty acids have been reported both in viral infections as well as alcoholic liver disease though such investigations have not addressed the adverse events with dual viral infection of HIV and HCV along with heavy drinking. This case report is of a patient with excessive alcohol drinking and first time diagnosis of HIV and HCV dual infection, elaborating concurrent alteration in Linoleic Acid (LA) levels and pro-inflammatory shift in ω-6/ω-3 ratio along with the elevations in liver injury markers. Elevated LA has been recently studied extensively for its role in alcoholic liver disease; and in the present case, we also found it to be clinically relevant to liver injury.

Hepatitis C virus increases the risk of kidney disease among HIV-positive patients: Systematic review and meta-analysis.

Kidney disease has become an important co-morbidity among human immunodeficiency virus-infected patients as they live longer in the era of highly effective antiretroviral therapy. It remains unclear how co-infection with hepatitis C virus impacts on the trajectory of kidney disease among HIV-infected patients. To evaluate the effect of co-infection with HCV on the risk of kidney disease in HIV-infected populations. We conducted a systematic review of the published medical literature to determine if hepatitis C co-infection is associated with increased likelihood of chronic kidney disease in HIV-positive adults. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis C virus across the published studies. Meta-regression and stratified analysis were also conducted. We identified 19 studies (146,151 unique patients with HIV) and separate meta-analyses were performed according to the outcome. Aggregation of longitudinal studies (n = 8, 105,462 unique patients) showed a relationship between HCV infection and increased risk of reduced glomerular filtration rate among HIV-infected individuals, the summary estimate for adjusted hazard ratio was 1.64 (95%CI, 1.28; 2.0, P < 0.001) in HIV-HCV co-infected individuals compared with those having HIV mono-infection. No between-studies heterogeneity was noted (P-value by Q test = 0.08). HCV positive serology was an independent risk factor for proteinuria; adjusted effect estimate, 1.23 (95% confidence interval, 1.18; 1.28, P = 0.001) (n = 6 studies; 26,835 unique patients). In meta-regression, we noted the impact of ageing (P = 0.0001) upon the adjusted hazard ratio of incidence of reduced glomerular filtration rate among HCV-HIV co-infected patients; a negative association between frequency of males (P = 0.001) and the adjusted hazard ratio of prevalence of low glomerular filtration rate was found. Hepatitis C co-infection is associated with a significant increase in the risk of reduced glomerular filtration rate and/or detectable proteinuria among HIV-infected individuals.

High serum HCV RNA in chronic hepatitis C patients coinfected with HIV despite successful antiretroviral therapy.

Baseline serum HCV RNA predicts treatment success in chronic hepatitis C patients. Thresholds at 0.8, 2, 4 and 6 million IU/ml discriminate treatment outcomes using distinct antiviral regimens. Compared to the general population, immunosuppressed individuals exhibit greater viral load values. This has been confirmed in HIV-HCV-coinfected patients, although little is known about the influence of antiretroviral therapy. Serum HCV RNA results recorded from all chronic hepatitis C patients who consecutively attended at our clinic were analysed. A total of 813 patients with detectable HCV RNA were identified. HIV coinfection was present in 78.7%, of whom 91% were on antiretroviral therapy. Overall, 467 (57%), 273 (34%), 170 (21%) and 127 (16%) had HCV RNA >0.8, >2, >4 and >6 million IU/ml, respectively. These high viral load values were found in 60%/36%/23%/18% of HIV-positive versus 47%/25%/11%/6% of HIV-negative individuals (P<0.01), respectively. In multivariate analysis, the greatest HCV RNA values were only significantly associated with HIV coinfection and HCV genotypes-1 or -4. Greater HCV RNA values were paradoxically found in HIV patients on than off antiretroviral therapy. Serum HCV RNA values above 0.8, 2, 4 and 6 million IU/ml are roughly seen in 47%, 25%, 11% and 6% of chronic hepatitis C monoinfected patients, respectively. Despite being on antiretroviral therapy, the corresponding figures are 1.3- to 3.0-fold greater in HIV-HCV-coinfected patients, who may benefit less frequently from shorter oral HCV treatment lengths.

Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection--The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index.

BackgroundIn Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis.MethodsWe evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA.ResultsOverall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08).ConclusionsHIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed.

Cannabis Use and Reduced Risk of Insulin Resistance in HIV-HCV Infected Patients: A Longitudinal Analysis (ANRS CO13 HEPAVIH).

Diabetes and insulin resistance (IR) is common in human immunodeficiency virus-hepatitis C virus (HIV-HCV)-coinfected patients, a population also concerned with elevated cannabis use. Cannabis has been associated with reduced IR risk in some population-based surveys. We determined whether cannabis use was consistently associated with reduced IR risk in HEPAVIH, a French nationwide cohort of HIV-HCV-coinfected patients. HEPAVIH medical and sociobehavioral data were collected (using annual self-administered questionnaires). We used 60 months of follow-up data for patients with at least 1 medical visit where IR (using homeostatic model assessment of insulin resistance [HOMA-IR]) and cannabis use were assessed. A mixed logistic regression model was used to evaluate the association between IR risk (HOMA-IR > 2.77) and cannabis use (occasional, regular, daily). Among the 703 patients included in the study (1287 visits), 323 (46%) had HOMA-IR > 2.77 for at least 1 follow-up visit and 319 (45%) reported cannabis use in the 6 months before the first available visit. Cannabis users (irrespective of frequency) were less likely to have HOMA-IR > 2.77 (odds ratio [95% confidence interval], 0.4 [.2-.5]) after adjustment for known correlates/confounders. Two sensitivity analyses with HOMA-IR values as a continuous variable and a cutoff value of 3.8 confirmed the association between reduced IR risk and cannabis use. Cannabis use is associated with a lower IR risk in HIV-HCV-coinfected patients. The benefits of cannabis-based pharmacotherapies for patients concerned with increased risk of IR and diabetes need to be evaluated in clinical research and practice.