HIV-HCV Coinfection Research Articles

Risk Factors for Hepatitis C Virus Reinfection After Sustained Virologic Response in Patients Coinfected With HIV.

Highly effective hepatitis C virus (HCV) therapies have spurred a scale-up of treatment to populations at greater risk of reinfection after sustained virologic response (SVR). Reinfection may be higher in HIV-HCV coinfection, but prior studies have considered small selected populations. We assessed risk factors for reinfection after SVR in a representative cohort of Canadian coinfected patients in clinical care. All patients achieving SVR after HCV treatment were followed with HCV RNA measurements every 6 months in a prospective cohort study. We used Bayesian Cox regression to estimate reinfection rates according to patient reported injection drug use (IDU) and sexual activity among men who have sex with men (MSM). Of 497 patients treated for HCV, 257 achieved SVR and had at least 1 subsequent RNA measurement. During 589 person-years of follow-up (PYFU) after SVR, 18 (7%) became HCV RNA positive. The adjusted reinfection rate (per 1000 PYFU) in the first year after SVR was highest in those who reported high-frequency IDU (58; 95% credible interval [CrI], 18-134) followed by MSM reporting high-risk sexual activity (26; 95% CrI, 6-66) and low-frequency IDU (22; 95% CrI, 4-68). The rate in low-risk MSM (16; 95% CrI, 4-38) was similar to that in reference patients (10; 95% CrI, 4-20). Reinfection rates did not diminish with time. HCV reinfection rates varied according to risk. Measures are needed to reduce risk behaviors and increase monitoring in high-risk IDU and MSM if HCV elimination targets are to be realized.

Community seroprevalence of hepatitis B, C and human immunodeficiency virus in adult population in gojjam zones, northwest Ethiopia

BackgroundIn Ethiopia, there is lack of data on the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immune deficiency virus (HIV) infections in adult population at community level. This study aimed at determining the HBV, HCV and HIV seroprevalence in adult population at community level in East and West Gojjam zones in Amhara region, Ethiopia.MethodsA cross-sectional study was conducted between October 01 and November 30, 2015. The Hepatitis B surface antigen (HBsAg) and anti-HCV were detected using the standard serological tests. The antibody to HIV infection was tested using the national HIV rapid tests algorithms.ResultsA total of 481 adults comprised of 51% females with median age of 25 years took part in the study. Overall, 7.5% (95% CI: 5.5–10.2%) of adult population were infected either with HBV, HCV and HIV. The prevalence of HBV was 15 (3.1%) and for HIV was 16 (3.3%). The seroprevalence of HCV was five (1.0%). HIV-HCV co-infection was found to be two (0.4%). HIV prevalence was higher in non-educated population than their counter parts (P = 0.001). HIV prevalence was high in housewives (6.0%) and merchants (4.7%).ConclusionsThis study revealed an intermediate HBV prevalence and low prevalence of HCV in adult population at community level. HIV prevalence is still a major public health problem in the area. To have the national data, we recommend further study on genotypes of HBV and HCV including local risk factors for transmissions. Moreover, health education on HBV, HCV and HIV transmission should be an intervention measure in the community.

Efficacy Of Pegylated Interferon And Ribavirin Treatment In Coinfected HIV HCV Patients

AbstractThe objectives of the study were to determine the efficacy of pegylated interferon alfa 2 b (PegINF) and ribavirin (RBV) treatment in co-infected HIV / HCV patients, to identify predictive factors associated with sustained viral response (SVR) in these patients. Out of the 956 HIV infected patients, 38 were HCVAb (4%) positive, 14 of which had undetectable HCV RNA, only 6 patients met the inclusion criteria. Screening failure was due to: liver cirrhosis Child Pugh B / C, hepatocellular carcinoma, pulmonary TB, thyroid dysfunction, CD4 <200 cells3, detectable HIV RNA and depressive syndrome. We initiated PegINF and RBV therapy for 48 weeks. SVR was achieved in 16.6% of cases (only one patient) and correlated with HCV RNA level, CD4 count, duration of HIV infection, CDC classification and liver fibrosis. In conclusion, our study group has a low prevalence of HIV / HCV co-infection (2.6%) with a large number of patients HCVAb positive but undetectable HCV RNA. Positive predictive factors for SVR were: low levels of HCV RNA, small duration of HIV infection, high levels of CD4, B1/B2 (CDC classification) and low degree of fibrosis.

HCV co-infection is associated with metabolic abnormalities among HAART naive HIV-infected persons

To determine the metabolic abnormalities among Hepatitis C Virus (HCV) co infected HAART naïve HIV infected persons within the adult ARV clinic of the University College Hospital/University of Ibadan, Ibadan, Nigeria Methods: This was a retrospective study involving the review of clinical records of newly recruited HIV-infected persons in the adult antiretroviral (ARV) clinic over a 12 month period (January - December 2006). Baseline results for fasting plasma glucose (FPG) and fasting lipid profile were retrieved. Out of the 1,260 HIV infected persons seen during the study period, HCV co-infection was found in 75 (6%) persons. The median values for total cholesterol, LDL-cholesterol and HDL-cholesterol were lower in the HCV co-infected persons. HIV-HCV co-infection was associated with a 0.31 mmol/L depression in Total Cholesterol (TC). The median FPG concentration was significantly higher in HIV-HCV co-infected than HIV only infected persons (5.33mmol/L vs. 5.00mmol/L, p = 0.047). However, regression analysis showed there was no relationship between the HIV-HCV co infected state and fasting glucose levels. HIV-HCV co-infection may be associated with a predictable decline in plasma cholesterol, but FPG may not be sufficient to demonstrate insulin resistance in these persons.

Human Immunodeficiency Virus (HIV) and Hepatitis Virus Coinfection among HIV-Infected Korean Patients: The Korea HIV/AIDS Cohort Study

BackgroundDespite declines in mortality and morbidity rates of patients with human immunodeficiency virus (HIV) infection as the result of highly active antiretroviral therapy, liver diseases due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are a leading cause of death among HIV-infected patients. However, HIV and HBV or HCV coinfection is still poorly documented, and more information is needed to better understand the characteristics of HIV-infected patients in Korea.Materials and MethodsA cross-sectional study was performed to investigate clinical characteristics and prevalence of HBV and HCV infection in HIV patients enrolled in the Korea HIV/acquired immune deficiency syndrome (AIDS) cohort study from 17 institutions between December 2006 and July 2013.ResultsAmong the 1,218 HIV-infected participants, 541 were included in this study. The prevalence of HBV-HIV and HCV-HIV coinfection was 5.0% (27/541) and 1.7% (9/541), respectively. There was no patient who was positive for both HBs antigen and HCV antibody. In multivariate logistic regression analysis, HBV unvaccinated status was a significant risk factor for HBV-HIV coinfection (odds ratio = 4.95, 95% confidence interval = 1.43–17.13).ConclusionsHBV and HCV infection was more common in HIV-infected persons enrolled in the Korean HIV/AIDS cohort, than in the general population in Korea.

Seroprevalence of hepatitis B virus/hepatitis C virus among human immunodeficiency virus-infected patients at a tertiary care teaching hospital in Mangalore, South India

Background: The human immunodeficiency virus (HIV) pandemic has continued to be a major public health problem even after more than three and a half decade of existence. According to the World Health Organization estimates, 36.7 million people were living with HIV by 2015 end while chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) occurs in 240 and 130–150 million people worldwide, respectively. Since the general modes of transmission are similar to HIV, coinfection of HIV with HBV/HCV is commonly found, being variable worldwide. Aims and Objectives: The aims and objectives of this study were (1) To investigate the seroprevalence of HBV/HCV in HIV-positive patients and (2) To analyze the demographic pattern and laboratory parameters. Settings and Design: This was a descriptive cross-sectional study. Materials and Methods: The serum samples from confirmed HIV-positive patients were screened and confirmed for HBV and HCV following standard operative procedures. The demographic pattern and laboratory parameters were also obtained. Statistical Analysis Used: SPSS software version 23.0 was used for statistical analysis. Results: The seroprevalence of HBV and HCV in HIV-positive patients was found to be 6.6% and 0.7%, respectively. Males (n = 7) were more commonly infected than females (n = 3) with the age group of 31–40 years being the most common and majority were married (n = 9). In HBV-HIV coinfection, the mean values of serum globulin, serum total bilirubin, conjugated bilirubin, aspartate amino-transferase, alanine aminotransferase (ALT), and alkaline phosphatase were increased, but in the only case of HCV-HIV coinfection, only hemoglobin and platelet count were decreased. A majority (n = 8) improved on discharge. Conclusions: The seroprevalence of HBV/HCV was high with laboratory test showing a significant correlation between HBV-HIV coinfection and serum globulin and ALT. Hence, creating awareness, understanding these diseases, and providing screening test in suspected individuals is the need of the hour which will improve the mortality rates related to them.

Epidemiological Study of HCV and HIV Infections in Relation to Certain Demographic Factors Among the Ante-Natal Population Within Kaduna Metropolis, Nigeria

Hepatitis C and HIV are blood borne infections of the human population including pregnant women globally. These Viruses are of global concern because of the significant challenges they pose to public health with over 36.7 million people leaving with HIV around the whole world. This research determined the prevalence of HCV, HIV and HCV-HIV co infection among pregnant women attending ante-natal in selected hospitals within the Kaduna metropolis. A total of 500 samples were collected from pregnant women on ante-natal in 5 different hospitals within the metropolis. One hundred samples were collected from each of the hospitals visited. Each sample was analyzed for HCV and HIV antibodies respectively using commercially available kits. Results analysis revealed prevalence rates of 1.4% for HCV, 5.80% for HIV and 0.40% HCV-HIV co-infection among the subjects. Chi square statistics for test of independence between 2 variables showed significant associations between HCV positivity and history of more than 2 sexual partners (p≤0.01), Age group between 36-40 years (p≤0.02), Unknown gestational age and 4-6 months respectively (p≤0.0002, p≤0.03). These were identified as potential risks for HCV contraction. On the other hand, there was no significant association between any of the demographic factors and HIV positivity which showed that exposure to the HIV causes infection regardless of any demographic factor. There is low prevalence of HCV, high prevalence of HIV and low prevalence of HCV-HIV co-infection among the ante-natal population within the metropolis.

Use of transient elastography in patients with HIV-HCV coinfection: A systematic review and meta-analysis.

Patients with HIV-hepatitis C virus (HCV) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals. This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment. Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through January 2016 to assess the diagnostic accuracy of transient elastography for liver stiffness in the HIV-HCV population. Included studies were analyzed according to the Cochrane DTA Working Group methodology. Bivariate and hierarchical models were used to compute pooled sensitivity and specificity. Positive and negative likelihood ratios were also determined. A Fagan nomogram was constructed. Meta-regression analysis was performed with assessment of publication bias using Deeks' funnel plot asymmetry testing. A total of six studies (n = 756) met the inclusion criteria. The diagnostic accuracy of elastography for the diagnosis of moderate (≥F2) fibrosis was 88% (95% confidence interval [CI], 0.85-0.90). The pooled sensitivity and specificity of moderate fibrosis was 97% (95% CI, 0.82-0.91) and 64% (95% CI, 0.45-0.79), respectively. The diagnostic accuracy of elastography for the assessment of cirrhosis was 94% (95% CI, 0.91-0.95). The pooled sensitivity and specificity for cirrhosis was 90% (95% CI, 0.74-0.97) and 87% (95% CI, 0.80-0.92), respectively. Meta-regression analysis demonstrated that CD4 cell count did not impact diagnostic accuracy of elastography. Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection.

Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, southeastern China.

This study aimed to investigate the epidemiological features of HIV-infected subjects co-infected with HBV/HCV in Fujian Province, southeastern China, and identify the risk factors. Blood samples were collected from 2,028 HIV antibody-positive subjects in Fujian Province. Serum HBsAg and anti-HCV antibody were detected, and CD4+ T cell count was measured. Of the 2,028 subjects, the prevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV co-infections was 16.22%, 3.7%, and 0.79%, respectively. Man (OR = 1.912, 95% CI: 1.371-2.667), key population (OR = 0.756, 95% CI: 0.57-0.976) and detainee (OR = 0.486, 95% CI: 0.259-0.909) were risk factors of HIV-HBV co-infection, and man (OR = 2.227, 95% CI: 1.096-4.525), minority (OR = 5.04, 95% CI: 1.696-14.98), junior high school or lower education (OR = 2.32, 95% CI: 1.071-5.025), intravenous drug use (OR = 38.46, 95% CI: 11.46-129.11) and detainee (OR = 5.687, 95% CI: 2.44-13.25) were risk factors of HIV-HCV co-infection. In addition, a lower mean CD4+ T cell count was measured in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects among the untreated individuals, while in the treated populations, a higher mean CD4+ T cell count was detected in HIV/HBV and HIV/HCV co-infected subjects than in HIV-infected subjects. HIV co-infection with HBV or HCV, notably HIV-HBV co-infection, is widespread in southeastern China. Hepatitis virus screening should be included in monitoring of HIV infection, and HIV and hepatitis virus co-infection should be considered during the development of HIV antiretroviral therapy scheme. J. Med. Virol. 89:443-449, 2017. © 2016 Wiley Periodicals, Inc.

During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy

Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown. We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy. We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes. These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection.

HIV-HCV Co-Infection among Multitransfused Thalassemic Individuals-A Review

Human immunodeficiency virus (HIV) and Hepatitis B and C virus (HBV and HCV) are three most common chronic viral pathogens among multitransfused thalassemic major individuals. HCV and HIV consist of a positive single stranded RNA genome, whereas HBV is a partially double stranded DNA virus. These viruses have similar routes of transmission, namely through blood and blood products, sharing of needles for injecting drugs. Co-infections of HIV in HCV positive patients are associated with reduced survival and an increased risk of progression to severe liver diseases with higher susceptibility towards hepato-toxicity due to antiretroviral therapy [2]. Co-infection is therefore common in people with high exposure to blood and blood products. The primary concern with HIV/HCV co-infection is that it can lead to more severe liver diseases and an increased risk for progression to liver cancer especially to immunocompromised thalassemic patients [3]. There are reports related to HCV and HIV co-infection from different parts of India, but no such detailed study on HCV and HIV co-infection among thalassemic patients [4,5].

HCV non-1b genotypes in injecting drug users from Romania

Chronic hepatitis C cases diagnosed in Romania were mostly related to unsafe parenteral treatments and blood transfusions; HCV genotype 1b was prevalent. During the last decade, an increasing number of HCV infections was reported among people who inject drugs (PWID). The aim of the current study was to test if this epidemiological shift triggered a diversification of the circulating viral strains. HCV genotypes were determined by reverse hybridization in 130 HCV-infected PWID (87.7% males; mean age 27.9 ± 6.7 years, injecting drugs for 8.1 ± 4.8 years). HIV-HCV co-infection was diagnosed in 80.8% of the subjects and 26.9% were HIV-HCV-HBV triple infected. Active HCV viral replication was present in 104 PWID (80%), more frequently in those HIV-co-infected (91.4% vs. 52% in HCV mono-infected, and 77.148.5% in HIV-HCV-HBV triple-infected, p = 0.0001). Non-1b genotypes were prevalent (54.8%), with subtype 1a the most commonly detected (24%), followed by genotypes 3a (14.4%) and 4 (7.7%). Mixed infections with genotypes 1a and 1b were found in nine subjects (8.7%). There was no difference in the genotypes frequencies based on HIV or HBV co-infection status, length of drug usage, or associated risk factors (tattoos, piercing, detention). The continuous surveillance of HCV genotypes in PWID from Romania will add valuable information to the overall European epidemiological picture, with important therapeutic implications.

Frequent injection cocaine use increases the risk of renal impairment among hepatitis C and HIV coinfected patients.

To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI). Prospective observational cohort study of HIV-HCV coinfected patients. Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70 ml/min per 1.73 m. Multivariate logistic regression was used to calculate odds ratios, and discrete-time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders. Eighty-seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (≥ 3 days/week) and frequent injection cocaine users (≥75% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort. After accounting for HCV RNA, frequent and cumulative injection cocaine abuse was associated with CRI progression and should be taken into consideration when evaluating impaired renal function in HIV-HCV coinfection.

Viral hepatitis and syphilis prevalence in persons who performed premarital blood tests in Argentina

The development of potent interferon-free regimens of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection has moved at a remarkable pace. Highly effective, extremely well-tolerated regimens are now available for most patient populations. Remarkably, advances have moved as quickly for those with HIV–HCV co-infection as for those with HCV monoinfection, with recent studies showing similar results with most regimens in both populations. This has raised the question of whether HIV co-infection continues to represent a “special” population among HCV-infected individuals. There are, however, some data suggesting that HIV may still impair responses in particularly difficult-to-cure populations. For example, attempts to shorten therapy to eight weeks with sofosbuvir/NS5A combinations have been at least somewhat less successful in HIV-co-infected patients than in those with HCV monoinfection. It is clear that innate and possibly adaptive immune function are still necessary for viral clearance even with highly effective DAA-based regimens, and thus, it is possible that particularly as therapy is pushed to shorter and simpler combinations, HIV may again emerge as an issue necessitating special consideration. The rationale behind DAA combinations will be reviewed with a focus on relevance for HIV-HCV co-infection. A general discussion of remaining issues to be addressed including drug interactions and treatment access will also be included.

Increased CD56(bright) NK cells in HIV-HCV co-infection and HCV mono-infection are associated with distinctive alterations of their phenotype.

BackgroundHIV-HCV co-infection is associated with accelerated progression to hepatic fibrosis, cirrhosis and hepatocellular carcinoma than HCV mono-infection. The contribution of innate immunity during HIV-HCV co-infection has been a relatively under-investigated area. Natural killer (NK) cells are pivotal sentinels of innate immunity against viruses and tumour cells. In this study we evaluated the effect of HIV-HCV co-infection on peripheral blood NK cell subsets with emphasis on the phenotype of CD56bright NK cells.MethodsSixty patients were included in the study; HIV mono-infected (n = 12), HCV mono-infected (n = 15), HCV-HIV co-infected (n = 21) and healthy controls (n = 16). PBMCs were isolated and immunophenotyping of NK cells was performed by flowcytometry.ResultsWe observed an expansion of CD56bright NK cell subset in HIV-HCV co-infection as compared to healthy controls and HIV mono-infected group. All the infected groups had an upregulated expression of the activating receptor NKG2D on CD56bright NK cells in comparison to healthy controls while not differing amongst themselves.The expression of NKp46 in HIV-HCV co-infected group was significantly upregulated as compared to both HIV as well as HCV mono-infections while NKp30 expression in the HIV-HCV co-infected group significantly differed as compared to HIV mono-infection. The CD56bright NK cell subset was activated in HIV-HCV co-infection as assessed by the expression of CD69 as compared to healthy controls but was significantly downregulated in comparison to HIV mono-infection. CD95 expression on CD56bright NK cells followed the same pattern where there was an increased expression of CD95 in HIV mono-infection and HIV-HCV co-infection as compared to healthy controls. In contrast to CD69 expression, CD95 expression in HCV mono-infection was decreased when compared to HIV mono-infection and HIV-HCV co-infection. Finally, expression of CXCR3 on CD56bright NK cells was increased in HIV-HCV co-infection in comparison to HIV mono-infection while remaining similar to HCV mono-infection.ConclusionThus, HIV-HCV co-infection is able to modulate the phenotype of CD56bright NK cell subset in a unique way such that NKp46 and CXCR3 expressions are distinct for co-infection while both mono-infections have an additive effect on CD56bright, CD69 with CD95 expressions. HCV mono-infection has a dominant effect on NKp30 expression while NKG2D and CD127 expressions remained same in all the groups.

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).

Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature.

To evaluate the extent of heterogeneity in global estimates of chronic hepatitis B (HBV) and C (HCV) cited in the published literature, we undertook a systematic review of the published literature. We identified articles from 2010 to 2014 that had cited global estimates for at least one of ten indicators [prevalence and numbers infected with HBV, HCV, HIV-HBV or HIV-HCV co-infection, and mortality (number of deaths annually) for HBV and HCV]. Overall, 488 articles were retrieved: 239 articles cited a HBV-related global estimate [prevalence (n=12), number infected (n=193) and number of annual deaths (n=82)]; 280 articles had HCV-related global estimates [prevalence (n=86), number infected (n=203) and number of annual deaths (n=31)]; 31 had estimates on both HBV and HCV; 54 had HIV-HBV co-infection estimates [prevalence (n=42) and number co-infected (n=12)]; and 68 had estimates for HIV-HCV co-infection [prevalence (n=40) and number co-infected (n=28)]. There was considerable heterogeneity in the estimates cited and also a lack of consistency in the terminology used. Although 40% of 488 articles cited WHO as the source of the estimate, many of these were from outdated or secondary sources. Our findings highlight the importance of clear and consistent communication from WHO and other global health agencies on current consensus estimates of hepatitis B and C burden and prevalence, the need for standardisation in their citation, and for regular updates.

12 Weeks of Daclatasvir in Combination With Sofosbuvir for HIV-HCV Coinfection (ALLY-2 Study): Efficacy and Safety by HIV Combination Antiretroviral Regimens.

Highly effective hepatitis C virus (HCV) direct-acting antiviral therapies that do not require modification of human immunodeficiency virus (HIV) antiretroviral regimens are needed. We evaluated the efficacy and safety of daclatasvir + sofosbuvir (DCV + SOF) for 12 weeks by antiretroviral (ARV) regimen in HIV-HCV-coinfected patients. In the randomized, open-label ALLY-2 study, HIV-HCV-coinfected patients received 8 or 12 weeks of once-daily DCV 60 mg (dose-adjusted as-necessary for concomitant ARVs) + SOF 400 mg. Results were stratified by ARV class for the 151 patients who received 12 weeks of DCV + SOF. Fifty-one patients were HCV treatment experienced, 100 were treatment naive, 89% male and 33% black. HCV genotypes were: genotype 1a (GT1a; 69%), GT1b (15%), GT2 (8%), GT3 (6%), and GT4 (2%). Sustained virologic response 12 weeks post-treatment (SVR12) was 97% and was similar across ARV regimens (P = .774): protease inhibitor-based, 97% (95% confidence interval [CI], 90%-99.7%); nonnucleoside reverse transcriptase inhibitor-based, 100% (95% CI, 91%-100%); and integrase inhibitor based, 95% (95% CI, 83%-99.4%). SVR12 among patients receiving either tenofovir disoproxil fumarate or abacavir as part of their antiretroviral therapy regimen was 98% (95% CI, 93%-99.5%) and 100% (95% CI, 85%-100%), respectively. Age, gender, race, cirrhosis, HCV treatment history, GT , and baseline HCV RNA did not affect SVR12. No discontinuations were attributed to treatment-related adverse events. DCV + SOF x12 weeks is a highly efficacious, all-oral, pan-GT HCV treatment for HIV-HCV coinfected patients across a broad range of ARV regimens. NCT02032888.

Responder Interferon λ Genotypes Are Associated With Higher Risk of Liver Fibrosis in HIV-Hepatitis C Virus Coinfection.

Background. Liver fibrosis progresses faster in individuals coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Interferon λ3 (IFN-λ3) has both antiviral and proinflammatory properties. Genotypes at IFNL single-nucleotide proteins (SNPs; rs12979860CC and rs8099917TT) are linked to higher HCV clearance, potentially via rs8103142. We examined the relationship between IFN-λ genotypes and significant liver fibrosis in HIV-HCV coinfection.Methods. From the prospective Canadian Co-infection Cohort (n = 1423), HCV RNA–positive participants in whom IFN-λ genotypes were detected and who were free of fibrosis, end-stage liver disease, and chronic hepatitis B at baseline (n = 485) were included. Time to significant fibrosis (defined as an aspartate transaminase level to platelet count ratio index [APRI] of ≥1.5) by IFN-λ genotypes was analyzed using Cox proportional hazards, with adjustment for age, sex, ethnicity, alcohol use, CD4+ T-cell count, HCV genotype, γ-glutamyl transferase level, and baseline APRI. Haplotype analysis was performed, with adjustment for ethnicity.Results. A total of 125 participants developed fibrosis over 1595 person-years (7.84 cases/100 person-years; 95% confidence interval [CI], 6.58–9.34 cases/100 person-years). Each genotype was associated with an increased fibrosis risk, with adjusted hazard ratios of 1.37 (95% CI, .94–2.02) for rs12979860CC, 1.34 (95% CI, .91–1.97) for rs8103142TT, and 1.79 (95% CI, 1.24–2.57) for rs8099917TT. Haplotype TCT was also linked with a higher risk (hazard ratio, 1.14 [95% CI, .73–1.77]).Conclusions. IFN-λ SNPs rs12979860, rs8099917, and rs81013142 were individually linked to higher rates of fibrosis in individuals with HIV-HCV coinfection. IFN-λ genotypes may be useful to target HCV treatments to people who are at higher risk of liver disease.

Prevalence and burden of HCV co-infection in people living with HIV: a global systematic review and meta-analysis

At global level, there are 37 million people infected with HIV and 115 million people with antibodies to hepatitis C virus (HCV). Little is known about the extent of HIV-HCV co-infection. We sought to characterise the epidemiology and burden of HCV co-infection in people living with HIV. In this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL+, POPLINE, Africa-wide Information, Global Health, Web of Science, and the Cochrane Library and WHO databases for studies measuring prevalence of HCV and HIV, published between Jan 1, 2002, and Jan 28, 2015. We included studies in HIV population samples of more than 50 individuals and recruited patients based on HIV infection status or other behavioural characteristics. We excluded editorials or reviews containing no primary data, samples of HCV or HIV-HCV co-infected individuals, or samples relying on self-reported infection status. We also excluded samples drawn from populations with other comorbidities or undergoing interventions that put them at increased risk of co-infection. Populations were categorised according to HIV exposure, with the regional burden of co-infection being derived by applying co-infection prevalence estimates to published numbers of HIV-infected individuals. We did a meta-analysis to estimate the odds of HCV in HIV-infected individuals compared with their HIV-negative counterparts. From 31 767 citations identified, 783 studies met the inclusion criteria, resulting in 902 estimates of the prevalence of HIV-HCV co-infection. In HIV-infected individuals, HIV-HCV co-infection was 2·4% (IQR 0·8-5·8) within general population samples, 4·0% (1·2-8·4) within pregnant or heterosexually exposed samples, 6·4% (3·2-10·0) in men who have sex with men (MSM), and 82·4% (55·2-88·5) in people who inject drugs (PWID). Odds of HCV infection were six times higher in people living with HIV (5·8, 95% CI 4·5-7·4) than their HIV-negative counterparts. Worldwide, there are approximately 2 278 400 HIV-HCV co-infections (IQR 1 271 300-4 417 000) of which 1 362 700 (847 700-1 381 800) are in PWID, equalling an overall co-infection prevalence in HIV-infected individuals of 6·2% (3·4-11·9). We noted a consistently higher HCV prevalence in HIV-infected individuals than HIV-negative individuals across all risk groups and regions, but especially in PWID. This study highlights the importance of routine HCV testing in all HIV-infected individuals, but especially in PWID. There is also a need to improve country-level surveillance of HCV prevalence across different population groups in all regions. WHO.