HIV-HCV Coinfection Research Articles

HIV-HBV and HIV-HCV Coinfection and Liver Cancer Development.

Liver diseases that are caused by the hepatitis B virus (HBV) and hepatitis C virus (HCV), including cirrhosis and hepatocellular carcinoma (HCC), have become increasingly important in patients infected with the human immunodeficiency virus (HIV) as their life expectancy is getting longer with successful anti-HIV therapy. Due to their shared transmission routes, dual infection by HIV and HBV or HIV and HCV, and triple infection by all three viruses are fairly common and affect millions of people worldwide. Whereas the immunodeficiency caused by HIV enhances the likelihood of HBV and HCV persistence, hepatotoxicity associated with anti-HIV therapy can worsen the liver diseases associated with HBV or HCV persistence. Evidence suggests HIV infection increases the risk of HBV- or HCV-associated HCC risk although the precise mechanisms of enhanced hepatocarcinogenesis remain to be fully elucidated. Recent success in curing HCV infection, and the availability of therapeutic options effective in long-term suppression of both HIV and HBV replication, bring hope, fortunately, to those who are coinfected but also highlight the need for judicious selection of antiviral therapies.

Impact of HBV and HCV coinfection on CD4 cells among HIV-infected patients: a longitudinal retrospective study

The impact of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on CD4 cells in patients with human immunodeficiency virus (HIV) is unclear. We aimed to examine the impact of HBV and HCV coinfection on CD4 cell count and CD4/CD8 ratio in adults with HIV. We conducted a longitudinal retrospective study in Brazil between January 1, 2002, and June 30, 2016, including 205 patients with HIV monoinfection, 37 with HIV-HBV coinfection, 35 with HIV-HCV coinfection, and 62 with HIV-HCV (48 HCV genotype 1 and 14 HCV genotype 3). Median duration of follow-up was 2,327 (interquartile range: 1,159-3,319) days. An increased CD4 cell count and CD4/CD8 ratio over time was observed in all groups receiving combined antiretroviral therapy (cART). Patients with HIV-HBV or HIV-HCV coinfection and those with HIV monoinfection, showed comparable CD4 cell counts and CD4/CD8 ratios during pre-ART. There was also no statistically significant difference in CD4/CD8 ratio between HIV-HBV or HIV-HCV coinfection groups and the HIV monoinfection group during follow-up on cART. However, CD4 cell counts were significantly lower in HIV-HCV patients than in HIV monoinfection patients during follow-up on cART. HIV patients with HCV genotype 3 coinfection showed significantly lower CD4/CD8 ratio during follow-up on cART than those coinfected with HCV genotype 1 coinfection. No statistically significant effect of coinfection was observed on the efficacy of cART. HIV-infected patients are more likely to show better immunological responses to cART when they are not coinfected with HCV.

2203. Risk Factors for Hepatitis C in Western Africa: An Observational Study in a STI Clinic

BackgroundThe pattern of hepatitis C virus (HCV) transmission routes in sub-Saharan Africa (SSA) has not been previously well characterized. A recent meta-analysis reported a general population HCV prevalence of 5.4% and HIV co-infection prevalence of 3.6% in SSA, with considerable regional variation.MethodsA cross-sectional study was performed in Kumasi, Ghana. Subjects were recruited from patients attending an STI clinic at a government-supported health center. Subjects completed a survey emphasizing known risk factors for HCV, including sexual behaviors, to capture potential routes of exposure. Surveys were administered in Twi, the local language, with the assistance of trained interpreters. Blood samples were collected and tested for HCV antibodies using DiaSpot Anti-HCV Rapid Screen Tests (USA). Data were analyzed using univariate analysis and logistic regression using SAS 9.4.ResultsOf the total 312 subjects, 15 were HCV positive (prevalence 4.8%). The HIV-HCV co-infection prevalence was 5.5%. After adjusting for age and sex, statistically significant associated risk factors for HCV infection (P < 0.05) include no/low level of education vs. tertiary (OR 5.0), northern region of birth vs. central region (OR 7.3), and traditional body scarring (OR 4.1). Rough sexual practices, ie dry sex, sores, were also explored and were associated with HCV infection (P = 0.02). Post-hoc stratified analysis of HIV-infected individuals (n = 201) was performed to identify risk factors among those with HCV co-infection. Significant risk factors (P < 0.05) in this sub-population include northern region of origin (OR 12.4) and traditional scars or marks (OR 4.6).ConclusionTwo risk factors for HCV infection, ie region of birth and traditional scarring, were significant in both the total clinic population and HIV co-infected individuals suggesting cultural practices are contributing to an increased risk of infection. Among HCV positive individuals, rough sexual practices were significant risk factors; whereas, IV-drug abuse was not. While HCV treatment exists, it is not currently available in West Africa; therefore, it is critical to identify risk factors to best target education programs and screening of populations to limit disease spread.Disclosures All authors: No reported disclosures.

Seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected patients in an HBV endemic area in Brazil.

BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) are a common cause of complications in liver disease and immunological impairment among human immunodeficiency virus (HIV)-infected patients. The aim of this study was to assess the seroprevalence of HBV and HCV and their correlation with CD4+ T-cells among HIV-infected patients in an HBV endemic area.MethodsA cross-sectional observational and retrospective study was carried out in a reference center in Southern Brazil between January 2005 and December 2016. Socio-demographic data were collected by using a structured questionnaire. Serological tests and analysis of CD4+ T-cell count levels were performed using standard procedures.ResultsThe seroprevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.10%, 3.10%, and 0.16%, respectively. At baseline, anti-hepatitis B surface and anti-hepatitis B core antigens were detected in 46.27% and 16.74% of HIV-monoinfected patients and in 31.25% and 21.86% of the HIV-HCV coinfected patients, respectively. The median CD4+ T-cell count at baseline in the HIV-monoinfected group was higher than that in the HIV-coinfected groups, but without statistical significance. The median CD4+ T-cell count and the CD4/CD8 ratio were significantly higher in HIV-HBV and HIV-HCV groups after 24 months of combination antiretroviral therapy (cART) compared to the pre-cART values. When comparing patients with HIV-HBV and HIV-HCV on cART, CD4+ T-cell recovery was more rapid for HIV-HBV patients.ConclusionAlthough the analyzed region was endemic for HBV, the prevalence of HIV-HBV and HIV-HCV coinfection was lower than the rate found in the general population of Brazil. HBV and HCV had no significant impact on CD4+ T-cell counts among HIV-infected patients at baseline.

Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence.

Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more efficacious with fewer adverse events, due to the availability of direct-acting antiviral agents, which target specific steps in the HCV life cycle. Recently, a combination regimen consisting of the HCV nonstructural protein 5A inhibitor elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and 4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed-dose combination table or single agent) for 12 or 16 weeks of treatment with or without ribavirin resulted in a high sustained virological response at 12 weeks in treatment-naïve and treatment-experienced patients with HCV Gt 1a, 1b, 4, or 6, including special populations, such as individuals with advanced chronic kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review, we focus on the mode of action, pharmacokinetics, clinical applications, efficacy, and safety profile of EBR/GZR, including special populations who have been considered refractory from the extensive evidence of clinical trials.

HUMAN IMMUNODEFICIENCY VIRUS-HEPATITIS C VIRUS COINFECTION: A REVIEW ON NECESSITY OF DIETARY COMPOUNDS FOR ANTIRETROVIRAL THERAPY

Human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection is a major health problem around worldwide. One-third of the HIV-infected patients suffer from chronic hepatitis (HCV). The risk factors of coinfected patients are very high while compared to the monoinfected patients; they are having higher HCV viral load is associated with a severe liver damage. The use of highly active antiretroviral therapy (HAART) dramatically increases the survival of HIV/HCV-coinfected patients by preventing the depletion of CD4 cell counts and delaying the progression of fibrosis which reduces the complications related to end-stage liver damage. Reverse-transcriptase inhibitors and protease inhibitors are very commonly used drugs for the treatment of coinfection. Combination drugs and synthetic drugs are playing a pivotal role in the coinfection therapy. Under HAART, the coinfected patients are affected by many adverse effects such as mitochondrial toxicity, hypersensitivity, and lipodystrophy syndrome. However, the adverse effects of most herbal drugs are relatively less frequent when the drugs are used properly compared with synthetic drugs; it may help to protect the patients from severe adverse effects. This review collates to the importance of plant-derived drugs for the treatment of HIV-HCV coinfection.

Injection drug use, food insecurity, and HIV-HCV co-infection: a longitudinal cohort analysis

ABSTRACTInjection drug use (IDU) and food insecurity (FI) are highly prevalent among individuals living with HIV-hepatitis C virus (HCV) co-infection. We quantified the association between IDU and FI among co-infected individuals using biannual data from the Canadian Co-infection Cohort (N = 608, 2012–2015). IDU (in the past six months) and IDU frequency (non-weekly/weekly in the past month) were self-reported. FI (in the past six months) and FI severity (marginal FI, moderate FI, and severe FI) were measured using the Household Food Security Survey Module. Generalized estimating equations were used to estimate risk ratios (RR) quantifying the associations between IDU, IDU frequency, and FI with Poisson regression. The associations between IDU, IDU frequency, and FI severity were quantified by relative-risk ratios (RRR) estimated with multinomial regression. At the first time-point in the analytical sample, 54% of participants experienced FI in the past six months, 31% engaged in IDU in the six months preceding the FI measure, and 24% injected drugs in the past month. After adjustment for confounding, IDU in the past six months (RR = 1.15, 95% confidence interval [CI] = 1.04–1.28) as well as non-weekly (RR = 1.15, 95% CI = 1.02–1.29) and weekly IDU (RR = 1.21, 95% CI = 1.07–1.37) in the past month are associated with FI. Weekly IDU in the past month is also strongly associated with severe FI (RRR = 2.68, 95% CI = 1.47–4.91). Our findings indicate that there is an association between IDU and FI, particularly weekly IDU and severe FI. This suggests that reductions in IDU may mitigate FI, especially severe FI, in this vulnerable subset of the HIV-positive population.

PIN62 - Aligned Strategies Identified by Prescribers and Managed Care to Close Treatment Decision Gaps in HCV and HIV

Despite the availability of effective treatments for HCV and HIV, persistent barriers have compromised achievement of patient health goals, including those related to misalignment in policies and practices among treatment decision-makers. This research is aimed at developing a conceptual model of HCV, HIV, or HCV-HIV co-infection therapy decision-making based on prescriber and managed care perspectives, by qualitatively assessing and describing (1) prescriber and managed care considerations for treatment access, treatment differentiation, and patient selection criteria, and (2) barriers to therapy prior-authorization (PA) processes and communication. Qualitative data were collected through trained scribes during 25 accredited education seminars held in 25 US cities, May—November 2017, combining prescriber and managed care professionals who manage patients with HCV and HIV. The discussion texts were analyzed using thematic analysis to generate a conceptual model of interprofessional practice and communication on therapy decision-making. Session data were collected from 270 prescribers and 211 managed care participants (combined sample: 44% pharmacists, 28% physicians, 29% NP/PAs). Findings revealed dominant themes: barriers were identified by both prescribers and managed care related to PA requirements, denials, and application of guidelines within therapy decisions. Specific forms of collaborative communication and practices were identified as aligned across both prescribers and managed care as mechanisms to close decision-making gaps: review guidelines and approval criteria, increase interprofessional communication, improve documentation and develop new protocols for PA submissions. This research suggests that a conceptual model of prescriber and managed care barriers to optimal care of patients with HCV, HIV, and co-infection includes interprofessional alignment on domains that warrant improvement, and discordance in role-specific considerations for decision-making. The findings support the importance of considering the conceptual alignments when developing practical strategies for improved communication among prescribers and managed care decision-makers. Research was supported through education grants from AbbVie and Gilead.

Hepatitis C Infection Among HIV-Positive Injection Drug Users and Non-Injection-Drug Users in Tajikistan

Background: HIV and Hepatitis C (HCV) infections are increasing in Tajikistan. While injection drug use (IDU) is a known risk factor for coinfection, little is known about non-injection drug users (NIDU). Objectives: The aim of this study was to identify factors associated with HIV-HCV coinfection and HIV infection alone among IDU and NIDU. Methods: Data from Tajikistan’s national HIV/AIDS registry data for all adults aged 18 years and older who had received a HCV test from 2006 to 2016 were obtained. Chi-square analyses identified factors associated with coinfection and injection drug use. Results: Of the 1849 people living with HIV who received a Hepatitis C test, 36.2% were positive for HCV and 63.8% were negative. Coinfection occurred among 74.4% of IDU and 18.5% of NIDU. In bivariate analyses, among both IDU and NIDU, coinfection was associated with urbanness of living location, having partner with a positive HIV test, marital status, region, and being imprisoned. Among IDU, coinfection was also associated with migrant status. Among NIDU, coinfection was also associated with gender, age at diagnosis, and AIDS stage at first diagnosis. Conclusions: This study shows that coinfection occurs most frequently among IDU in general, but that NIDU represent an important population deserving of additional study and tailored HIV and HCV prevention programs. Additional research to identify best practices for targeting NIDU and people living in at-risk regions for screening and are required to effectively prevent and then appropriately manage coinfection.

Matrix stiffness regulate apoptotic cell death in HIV-HCV co-infected hepatocytes: Importance for liver fibrosis progression

HIV-HCV co-infection causes rapid progression of liver fibrosis. These outcomes to liver cirrhosis can be improved, but not stopped by specific antiviral therapies. Due to high significance of HIV-HCV interactions for morbidity and mortality in co-infected patients, our attention was attracted to the multi-component pathogenesis of fibrosis progression as the transition to end-stage liver disease development. In this study, we hypothesize that increased matrix stiffness enhances apoptosis in HCV-HIV-co-infected hepatocytes and that capturing of apoptotic bodies (AB) derived from these infected hepatocytes by hepatic stellate cells (HSC) drives the fibrosis progression. As the source of viruses, JFH1 (HCV genotype 2a) and HIV-1ADA (either purified or containing in infected macrophage supernatants) were chosen. Using Huh7.5-CYP (RLW) cells and primary human hepatocytes mono-infected with HCV and HIV or co-infected, we have shown that both HCV and HIV RNA levels were increased in co-infected cells, which was accompanied by hepatocyte apoptosis. This apoptosis was attenuated by azidothymidine treatment. The levels of both infections and apoptosis were more prominent in primary hepatocytes cultured on substrates mimicking fibrotic stiffness (24 kPa-stiff) compared to substrates mimicking healthy liver (2.4 kPa-soft). The engulfment of AB from pathogen-exposed hepatocytes activated pro-fibrotic mRNAs in HSC. Overall, the increased matrix stiffness is not only a consequence of liver inflammation/fibrosis, but the condition that further accelerates liver fibrosis development. This is attributed to the switching of HSC to pro-fibrotic phenotype by capturing of excessive amounts of apoptotic HCV- and HIV-infected hepatocytes.

Effectiveness and security of chronic hepatitis C treatment in coinfected patients in real-world.

Background HIV-HCV coinfection produces high morbi-mortality. Direct-acting antivirals (DAAs) have shown high efficacy, although special attention should be paid to the risk of drug interactions. However, due to the lack of representativeness of coinfected patients in clinical trials, it is important to know real-world results. Objective To evaluate DAA treatment effectiveness in coinfected patients. We also analyse safety profile of DAA treatment and drug interactions between HCV and HIV therapy. Setting Descriptive study carried in a tertiary hospital of Spain Method HIV-HCV coinfected patients treated with DAAs between November 2014 and June 2016 were included. Main outcome measure Efficacy was measured in terms of sustained virologic response at week 12 after the end of therapy. Adverse events that led to treatment discontinuation were registered to evaluate the safety profile, and also drug interactions between DAAs and antiretroviral treatment were evaluated. Results Main HCV genotypes were 1a (34.9%) and 4 (24.5%). 51.9% were HCV previously treated, 54.7% had grade 4 liver fibrosis. SVR12 was reported in 90.6%. HCV treatment was well tolerated and there were no discontinuations because of adverse events. 30.2% of HIV treatments had to be modified before DAA treatment was started due to interactions, HIV suppression was not compromised. Conclusion DAA treatment in coinfected patients seems to be highly effective and secure. Evaluation of drug interactions must be a priority in order to maximize effectiveness and avoid toxicity.

Methadone treatment, severe food insecurity, and HIV-HCV co-infection: A propensity score matching analysis

BackgroundSevere food insecurity (FI) is common among individuals living with HIV-hepatitis C virus (HCV) co-infection. We hypothesize that the injection of opioids is partly responsible for the association between injection drug use and severe FI. Therefore, this analysis examines whether methadone maintenance treatment for opioid dependence is associated with a lower risk of severe FI. MethodsWe used biannual data from the Canadian Co-infection Cohort (N = 608, 2012–2015). Methadone treatment (exposure) was self-reported and severe FI (outcome) was measured using the Household Food Security Survey Module. To quantify the association between methadone treatment and severe FI, we estimated an average treatment effect on the treated (marginal risk difference [RD]) using propensity score matching. ResultsAmong participants, 25% experienced severe FI in the six months preceding the first time-point in the analytical sample and 5% concurrently reported receiving methadone treatment. Injection of opioids in the six months preceding the treatment and outcome measurements was much higher among those who received methadone treatment (39% vs. 12%). Among the treated participants, 97% had injected opioids in their lifetimes. After propensity score matching, the average risk of experiencing severe FI is 12.3 percentage-points lower among those receiving methadone treatment, compared to those who are not receiving treatment (marginal RD = −0.123, 95% CI = −0.230, −0.015). ConclusionsAfter adjustment for socioeconomic, sociodemographic, behavioural, and clinical confounders, methadone treatment is associated with a lower risk of severe FI. This finding suggests that methadone treatment may mitigate severe FI in this vulnerable subset of the HIV-positive population.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people

ABSTRACTDepressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300–665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

Modeling HIV-HCV coinfection epidemiology in the direct-acting antiviral era: the road to elimination

BackgroundHCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model.MethodsThe model was based on epidemiological data from the French Dat’AIDS cohort. Eight risk groups were considered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals, intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence data observed in the cohort between 2012 and 2015.ResultsOn January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosed patients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatment coverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalence among HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCV prevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalence in HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70% would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients would account for 34% of HCV infections in 2026.ConclusionsOur model suggests that DAA could nearly eliminate coinfection in France within 10 years for most risk groups, including LR MSM. Elimination in HR MSM will require increased TC.

Mechanisms of Accelerated Liver Fibrosis in HIV-HCV Coinfection

Although there is evidence that HCV progresses rapidly in HIV/HCV coinfected patients in comparison with HCV monoinfected, the HIV-, HCV- and host/genetic-related factors, as well as the exact mechanisms implicated in this process are not fully elucidated. Furthermore, cure of HCV in those coinfected seems possible with the new antiviral drugs, but high cost as well as insufficient identification, linkage with care and treatment hamper the achievement of this goal. Research on the subject, could reveal an important prognostic marker for the effectiveness of persuasion of patients with HIV/HCV coinfection with a predicted accelerated fibrosis course, in order to facilitate and prioritize, not in terms of guidelines but in the real life situation, their treatment with a medically just framework.

Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A): two randomised, phase 2, open-label trials

New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3. Part A of these phase 2, randomised, multicentre, open-label, clinical trials enrolled participants from 11 countries, aged 18 years or older, chronically infected with HCV genotypes 1, 2, or 3, with HCV RNA of at least 10 000 IU/mL, without evidence of cirrhosis, who had not received previous treatment for HCV infection. Within each HCV genotype, participants were randomly assigned (1:1:1:1) with a block size of 4, to open-label treatment to one of four treatment groups: grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (300 mg/day); grazoprevir (100 mg/day) plus ruzasvir (60 mg/day) plus uprifosbuvir (450 mg/day); grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (300 mg/day); or grazoprevir (100 mg/day) plus elbasvir (50 mg/day) plus uprifosbuvir (450 mg/day), according to a computer-generated allocation schedule. Randomisation was centrally implemented using an interactive voice response system and integrated web response system. The primary endpoint was the proportion of participants achieving sustained virological response at 12 weeks (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the end of all study therapy) in the per-protocol analysis set, which included all participants who were randomised and received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT02332707 and NCT02332720. 241 participants were randomised between Feb 18, 2015, and March 16, 2015. 240 participants completed 8 weeks of treatment and reached follow-up 12 weeks after the end of treatment. Of the four regimens, grazoprevir plus ruzasvir plus uprifosbuvir 450 mg had the most consistently high SVR12 (>90%) for participants infected with genotype 1 (21 [91%] of 23), genotype 2 (15 [94%] of 16), and genotype 3 (20 [91%] of 22). In particular, among those with genotype 2 infection, the grazoprevir plus ruzasvir plus uprifosbuvir 450 mg regimen had a higher SVR12 (15 [94%] of 16) than the grazoprevir plus ruzasvir plus uprifosbuvir 300 mg regimen (ten [71%] of 14), grazoprevir plus elbasvir plus uprifosbuvir 300 mg regimen (11 [69%] of 16), or grazoprevir plus elbasvir plus uprifosbuvir 450 mg regimen (nine [60%] of 15). Overall, the most common adverse events were headache (55 [23%] of 240), fatigue (47 [20%] of 240), and nausea (32 [13%] of 240). Two (<1%) of 240 participants had serious adverse events (pharyngeal abscess and keratitis), which were not considered drug related by the respective investigators. These results support further evaluation of the three-drug direct-acting antiviral agent regimen of grazoprevir 100 mg plus ruzasvir 60 mg plus uprifosbuvir 450 mg among a more diverse HCV-infected population, including those with compensated cirrhosis, previous treatment with an interferon-containing regimen, and HCV-HIV co-infection. Merck & Co, Inc.

HIV Coinfection

Improved screening of the blood supply and safer injection practice have led to a decreased prevalence of hepatitis C virus (HCV) worldwide over the past decade. However, those who are coinfected with HIV and HCV experience synergistic interaction between the viruses, leading to accelerated liver fibrosis and possibly increased HIV progression. Left untreated, these coinfected patients experience higher mortality compared with monoinfected individuals. The recent availability of highly efficacious direct-acting antivirals (DAAs) provides opportunity to prioritize coinfected patients for curing HCV, which can improve liver-related and overall mortality. This review summarizes the epidemiology, virology, and natural history of coinfection. Major clinical trials involving coinfected patients are summarized, and drug-drug interactions between HIV antiretroviral therapy and HCV DAA therapy are discussed. Given the numbers of people at risk for primary infection and reinfection after cure, we also discuss important strategies of harm reduction and treatment as prevention. The revolution in DAAs provides the prospect of reducing the burden of liver disease, which remains one of the leading causes of death in people living with HIV. Key words: HIV-HCV coinfection; Epidemiology; Natural history; Viral interaction; Direct-acting antiviral; Drug-drug interaction

Update in HIV-hepatitis C virus coinfection in the direct acting antiviral era.

Availability of direct acting antivirals (DAAs) that demonstrate remarkable clinical efficacy and safety has revolutionized the ability to treat chronic infection with hepatitis C virus (HCV). An equal measure of clinical success has now been achieved in persons coinfected with HCV and the HIV, a historically harder to cure cohort with interferon-based therapy. Global goals include identifying all HIV-HCV-infected persons, gaining access to DAA therapy, preventing de novo and reinfection, and managing the sequelae of chronic infection. This review will discuss advances in the field of HIV-HCV coinfection reported during the last 18 months, and will suggest areas for future investigation. An expanding body of literature has enhanced our understanding of the clinical and epidemiologic issues surrounding HIV-HCV coinfection. DAA therapy for HCV is highly efficacious in HIV-HCV-coinfected persons if drug-drug interactions are appropriately considered. Eradicating HCV infection in persons with HIV coinfection can be achieved safely and effectively with available DAAs. Economic and social approaches to enable access and delivery of curative HCV therapy to HIV-infected persons require continued research and resource allocation.

Chronic Hepatitis C Treatment : A Systematic Review

Background: Chronic hepatitis C (CHC) infection affects almost 3% of the global population and can lead to cirrhosis, liver failure, and hepatocellular carcinoma in a significant number of those infected. Thus, there is a complelling need to develop and introduce new therapeutics with a direct-acting antiviral effect in order to target various stages of the HCV lifecycle for HCV eradication without concomitant interferon. Study Objective: to provide treatment recommendations for chronic HCV for specialists and generalists based on published evidence. Methods: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, Google Scholar, and Oaister was conducted from 1990 to 2016, records were filtered according to the Inclusion criteria and 27 hits were yielded. Results: Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89%-90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3 should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks’ duration: 82%-93%; SVR for genotype 3, 24 weeks’ duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients. Conclusion: A growing body of evidence suggests that recently developed HCV combined treatment modalities have transformed chronic HCV into a routinely curable disease being relatively available and well tolerated ,which can potentially reduce the need for liver transplantation and reduce HCV-related mortality. Treatment protocol for genotype1 is based on a combined regimen of Pegylated interferons with ribavirin and sofosbuvir or simeprevir while Sofosbuvir with ribavirin alone should be used to treat patients infected with HCV genotypes 2 and 3. Patients coinfected with human immunodefiency virus and HCV genotype 1 should be treated for HCV with pegylated interferons, ribavirin, and sofosbuvir by a physician with experience in treating this particular group of patients and familiar with potential drug interactions.

Suicide risk in a representative sample of people receiving HIV care: Time to target most-at-risk populations (ANRS VESPA2 French national survey).

BackgroundSuicide risk is high among people living with HIV (PLHIV). This study aimed to identify major correlates of suicide risk in a representative sample of PLHIV in France, in order to help target individuals who would benefit from suicide risk screening and psychiatric care.MethodsThe ANRS VESPA2 cross-sectional survey (April 2011-January 2012) collected socio-demographic, medical and behavioral data from 3,022 PLHIV recruited in 73 French HIV hospital departments. The study sample comprised the 2,973 participants with available self-reported data on suicide risk (defined as having either thought about and planned to commit suicide during the previous 12 months or attempted suicide during the same period of time) and medical data on comorbidities. Weighted Poisson models adjusted for HCV co-infection and significant clinical variables were used to estimate the relationship between suicide risk and HIV transmission groups, experience with HIV disease and other psychosocial factors.ResultsSuicide risk was reported by 6.3% of PLHIV in the study sample. After adjustment for HIV immunological status and HCV co-infection, women (IRR [95%CI]:1.93 [1.17; 3.19]) and men who have sex with men (MSM) (1.97 [1.22; 3.19]) had a higher suicide risk than the rest of the sample. Moreover, the number of discrimination-related social contexts reported (1.39 [1.19; 1.61]), homelessness (4.87 [1.82; 13.02]), and reporting a feeling of loneliness (4.62 [3.06; 6.97]) were major predictors of suicide risk.ConclusionsReducing the burden of precarious social conditions and discrimination is an important lever for preventing suicide risk among PLHIV in France. Comprehensive care models involving peer/community social interventions targeted at women and MSM need to be implemented to lower the risk of suicide in these specific subgroups of PLHIV.