Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV‐infected patients

Background

Among HIV‐infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes.

Methods

We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV‐infected US veterans in the highly active antiretroviral therapy (HAART) era (1996–2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time‐dependent variable.

Results

A total of 19 424 HIV‐infected patients [31.6% of whom were HCV‐coinfected (HIV/HCV)] contributed 76 376 patient‐years of follow‐up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV‐only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV‐only patients: 4.19 vs. 3.36 events/1000 patient‐years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient‐years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98–1.61; P=0.072] for AMI and 1.20 (CI 1.04–1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model.

Conclusions

In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV‐infected patients.     

Hepatitis C/HIV co‐infection is associated with higher mortality in hospitalized patients with Hepatitis C or HIV

Summary. Up to 10% of all patients with Hepatitis C virus (HCV) infection are co‐infected with human immunodeficiency virus (HIV); 25–30% of HIV patients are co‐infected with HCV. The aim of this study was to examine the association of HCV/HIV co‐infection with outcomes of hospitalized patients compared to those with HCV or HIV monoinfection. Using the 2006 Nationwide Inpatient Sample, patients with HCV or HIV monoinfection or HCV/HIV co‐infection were identified using ICD‐9‐CM codes. We compared liver‐related and infection‐related admission between the three groups of patients. Multivariate logistic regression was performed to identify independent predictors of in‐hospital mortality. A total of 474 843 discharges with HCV monoinfection, 206 758 with HIV monoinfection and 56 304 with HCV/HIV co‐infection were included. Liver‐related admissions were more common in co‐infected patients (15.4%) compared to those with HIV monoinfection (3.3%, P < 0.001). Primary infectious hospitalizations were more common in HIV monoinfection (33.9%) compared to co‐infected patients (26%, P < 0.001). HCV/HIV co‐infection was associated with higher mortality compared to HCV monoinfection (OR 1.41, 95% CI 1.20–1.65) but not when compared to monoinfected‐HIV patients. HCV‐associated cirrhosis or complications thereof conferred four times greater mortality risk in patients with HIV (OR 3.96, 95% CI 3.29–4.79). The rate of hospitalization for HCV/HIV co‐infected patients (23.5%) was significantly higher than those with HCV (14.8%) or HIV (19.9%) (P < 0.001). HCV/HIV co‐infection is associated with significantly higher rates of hospitalization and is a risk factor for in‐hospital mortality compared to patients with isolated HCV.     

Stronger hepatitis C virus‐specific CD8+ T‐cell responses in HIV coinfection

Summary. Hepatitis C virus (HCV) is a widespread chronic infection that shares routes of transmission with human immunodeficiency virus (HIV). Thus, coinfection with these viruses is a relatively common and growing problem. In general, liver disease develops over years with HIV coinfection, when compared to decades in HCV monoinfection. The role of the immune system in the accelerated pathogenesis of liver disease in HIV/HCV coinfection is not clear. In this study, we compared the frequency, magnitude, breadth and specificity of peripheral blood CD4⁺ and CD8⁺ T‐cell responses between HCV‐monoinfected and HCV/HIV‐coinfected individuals and between HIV/HCV‐coinfected subgroups distinguished by anti‐HCV antibody and HCV RNA status. While HIV coinfection tended to reduce the frequency and breadth of anti‐HCV CD8⁺ T‐cell responses in general, responses that were present were substantially stronger than in monoinfection. In all groups, HCV‐specific CD4⁺ T‐cell responses were rare and weak, independent of either nadir or concurrent CD4⁺ T‐cell counts of HIV‐infected individuals. Subgroup analysis demonstrated restricted breadth of CD8⁺ HCV‐specific T‐cell responses and lower B‐cell counts in HIV/HCV‐coinfected individuals without anti‐HCV antibodies. The greatest difference between HIV/HCV‐coinfected and HCV‐monoinfected groups was substantially stronger HCV‐specific CD8⁺ T‐cell responses in the HIV‐coinfected group, which may relate to accelerated liver disease in this setting.     

Interleukin 10 Responses Are Associated With Sustained CD4 T-Cell Counts in Treated HIV Infection

Background.Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non-AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART). Methods.A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/μL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2-4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation. Results.Undetectable HIV RNA (<80?copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation. Conclusions.Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.     

HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms

Chronic hepatitis C virus (HCV) infection has become a major threat to the survival of human immunodeficiency virus (HIV)-infected persons in areas where antiretroviral therapy is available. In coinfection, viral eradication has been difficult to attain, and HCV therapy is underused. Novel therapies may be particularly beneficial for this population, yet studies lag behind those for HCV monoinfection. Increasingly, incident HCV among HIV-infected men who have sex with men is associated with sexual risk behavior further research should be performed to refine understanding of the causal mechanism of this association. The phenomenon of aggressive hepatic fibrogenesis when HIV infection precedes HCV acquisition requires longer-term observation to ensure optimal timing of HCV therapy. Medical management in coinfection will be improved by enhancing HCV detection, with annual serologic testing, screening with HCV RNA to detect acute infection, and HIV testing of HCV-infected individuals; by addressing HCV earlier in coinfected persons; and by universal consideration for HCV therapy. HCV drug trials in individuals coinfected with HIV should be expedited. HIV/HCV coinfection remains a growing and evolving epidemic; new developments in therapeutics and improved care models offer promise.     

Analysis of the efficacy of treatment with peginterferon α‐2a and ribavirin in patients coinfected with hepatitis B virus and hepatitis C virus

Objective: To study the virological features of patients coinfected with hepatitis B virus (HBV) and hepatitis C virus (HCV) and the efficacy of combination therapy with peginterferon α‐2a and ribavirin in these patients. Methods: The epidemiological and virological data of 50 patients coinfected with HBV and HCV were analysed. The virological response rates of patients treated with peginterferon α‐2a and ribavirin between the HBV and HCV coinfection group and the HCV monoinfection group were compared. Results: HCV‐dominant virus strains accounted for 92.0% of the 50 coinfected individuals, and HCV‐ and HBV‐dominant virus strains accounted for the remaining 8.0%. The HBV DNA level of the patients coinfected with HBV and HCV was 4.6±0.9 log₁₀ copies/ml, which was significantly lower than that in the HBV monoinfection group (5.9±1.2 log₁₀ copies/ml) (t=5.964, P<0.01). The HBeAg‐positive rate (12.0%, 6/50) of the coinfection group was significantly lower than (45.3%, 19/42) that of the HBV monoinfection group (χ²=12.743, P<0.01). The partial early virological response (pEVR) rate and the end‐of‐treatment virological response (ETVR) rate (50.0%, 15/30; 90.0%, 27/30) of patients with genotype 1 in the coinfection group were significantly higher than those (16.0%, 4/25; 56.0%, 14/25) in the HCV monoinfection group (χ²=6.971, P=0.008; χ²=8.307, P=0.004). The relapse rate (55.6%, 15/27) of patients with genotype 1 in the coinfection group was significantly higher than that (21.4%, 3/14) in the HCV monoinfection group (χ²=4.360, P=0.037). The sustained virological response (SVR) rate (40.0%, 12/30) of patients with genotype 1 in the coinfection group was compared with that of the HCV monoinfection group (44.0%, 11/25) (χ²=0.090, P=0.765). There was no significant difference in the on‐treatment virological response, ETVR, SVR and relapse rates between two groups for patients with genotype 2. The incidence of side effects (30%, 15/50) of patients in the coinfection group was significantly higher than that (13%, 6/46) in the HCV monoinfection group (χ²=4.031, P=0.045). The reactivation rate of HBV DNA (33.3%, 9/27) with HCV SVR was significantly higher than that of patients without SVR (8.7%, 2/23) (χ²=4.393, P=0.036). Conclusions: The replication of HBV was suppressed, and HCV was the dominant virus strain. Compared with HCV‐monoinfected patients, pEVR, ETVR and relapse rates of patients with genotype 1 in the coinfection group were high, while they shared similar SVR rates. HBV and HCV coinfection had no impact on the rate of virological response for genotype 2.     

HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV

We examined the impact of HBV/HIV coinfection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV monoinfection or HBV/HIV coinfection using ICD‐9‐CM codes. We compared liver‐related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in‐hospital mortality, length of stay and total charges. A total of 72 584 discharges with HBV monoinfection, 133 880 discharges with HIV monoinfection and 8156 discharges with HBV/HIV coinfection were included. HBV/HIV coinfection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30–2.15) but not when compared to HIV monoinfection (OR 1.22, 95% CI 0.96–1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with three times greater in‐hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95% CI 1.80–5.02). Length of stay and total hospitalization charges were greater in the HBV‐/HIV‐coinfected group compared to the HBV monoinfection group (+1.53 days, P < 0.001; $17595, P < 0.001) and the HIV monoinfection group (+0.62 days, P = 0.034; $8840, P = 0.005). In conclusion, HBV/HIV coinfection is a risk factor for in‐hospital mortality, particularly in liver‐related admissions, compared to HBV monoinfection. Overall healthcare utilization from HBV/HIV coinfection is also higher than for either infection alone and higher than the national average for all hospitalizations, thus emphasizing the healthcare burden from these illnesses.     

HBV coinfection with HCV alters circulating Tfh cell distribution and impairs HCV neutralizing antibody responses

Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection reciprocally influences viral replication and host defence responses. This study aimed to investigate the impact of HBV coinfection on circulating T follicular helper cell (cTfh) distribution and the HCV neutralizing antibody (nAb) response. HCV neutralizing antibody responses were measured in individuals with HCV monoinfection (n = 83) and HBV/HCV coinfection (n = 78) using the HCV pseudoparticle neutralization assay. The frequencies of cTfh cells and their subsets in HCV monoinfection (n = 34) and HBV/HCV coinfection (n = 30) were analysed by flow cytometry. The correlations of clinical parameters, cTfh cells and neutralizing antibody responses were analysed. Compared with HCV monoinfection, the HBV coinfection group showed significantly lower HCV neutralizing antibody responses (P < 0.001) and a decreased frequency of circulating Th1‐like Tfh cells (Tfh1) (P = 0.004). In HCV monoinfection, the frequency of the Tfh1 subset was positively correlated with HCV neutralizing antibody responses (R = 0.378, P = 0.03), but this correlation was lost under HBV/HCV coinfection (R = 0.115, P = 0.551). In contrast, the frequency of circulating Th2‐like Tfh cells (Tfh2) was negatively correlated with the HCV neutralizing antibody responses (R = 0.404, P = 0.003). Further analysis showed that HBV coinfection enhanced the Tfh2 subset composition within cTfh cells (P < 0.001), which was associated with serum HBsAg in HBV/HCV coinfection (R = 0.521, P = 0.003). As expected, HBsAg also exhibited an inverse association with HCV neutralizing antibody responses in HBV/HCV coinfection (R = 0.59, P < 0.001). In contrast to HCV monoinfection, HBV/HCV coinfection leads to altered cTfh cell distribution and impaired HCV neutralizing antibody responses, which are associated with HBsAg. These findings will be helpful for better understanding the immunopathogenesis of HBV/HCV coinfection.     

Racial difference in mortality among U.S. veterans with HCV/HIV coinfection

OBJECTIVES: This study was performed to examine the impact of viral coinfections and race on clinical and virological outcome of hepatitis C virus (HCV) infection. METHODS: Three groups of patients (265 HCV/HIV coinfected, 251 HCV monoinfected, 227 HIV monoinfected) were identified between 2000 and 2002 from the computerized patient record system at the Philadelphia VA Medical Center and analyzed for clinical and virological parameters. RESULTS: HCV/HIV coinfection was associated with higher frequency of liver function abnormalities (37% vs 21% vs 20%; p < 0.0003) and greater mortality (17% vs 6% vs 9% over 3 yr period, p = 0.0003, p = 0.027) compared to HCV or HIV monoinfection, respectively. However, HCV/HIV coinfection was not associated with worsened HIV-related parameters (CD4 count, HIV titer, and use of antiretroviral therapy) or increased HCV titers compared to HIV or HCV monoinfection in our population, respectively. Interestingly, mortality among HCV/HIV coinfected patients was significantly greater in white than in black patients (31% vs 15%, p = 0.011). This racial disparity in mortality was not apparent in the monoinfected groups and not explained by HBV coinfection or history of alcohol use disorder. CONCLUSIONS: We conclude that HCV/HIV coinfection is associated with worsened liver disease and higher mortality than HCV- or HIV-monoinfection without directly influencing CD4 count and HCV or HIV titers. Furthermore, we demonstrated a racial disparity in survival of HCV/HIV-coinfected patients that needs further investigation.     

Quantification of hepatic FOXP3+ T‐lymphocytes in HIV/hepatitis C coinfection

Coinfection with HIV adversely impacts every stage of hepatitis C (HCV) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T‐regulatory (Treg) cells (CD4+ and FOXP3+) are hypothesized to limit hepatic damage in HCV. Our hypothesis was that reduced frequency of hepatic Treg in HIV/HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP3+, CD4+, CD8+ and CD20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV/HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV/HCV coinfected subjects had fewer hepatic FOXP3+ (P = 0.031) and CD4+ cells (P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD8+ cells compared with HCV monoinfected (P = 0.023), and a lower ratio of FOXP3+ to CD8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD4+ cells controlled for differences in number of FOXP3+ cells. Fewer hepatic FOXP3+ and CD4+ cells in HIV/HCV coinfection compared with HCV monoinfection suggests lower Treg activity, driven by an overall loss of CD4+ cells. Higher number of CD8+ cells in HIV/HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV/HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients.     

Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection

BACKGROUND/AIMS: Although steatosis is strongly associated with hepatitis C virus (HCV) infection, little is known about this finding in patients coinfected with human immunodeficiency virus (HIV) and HCV. The aims of the present study were to determine the prevalence and severity of steatosis in HIV/HCV coinfected patients. METHODS: Consecutive patients undergoing liver biopsy were prospectively identified and were interviewed to obtain detailed demographic and clinical data. Steatosis was scored according to the percentage of hepatocytes involved: 0 (none), 1 (<33%), 2 (33-66%), or 3 (>66%); fibrosis was scored on a scale from 0 to 4. RESULTS: A total of 708 patients were enrolled, including 154 with HIV/HCV coinfection and 554 with HCV monoinfection. Steatosis of any grade (72.1 vs. 52.0%, P<0.001), grade 2/3 steatosis (48.1 vs. 20.2%, P<0.001), and stage 3/4 fibrosis (43.5 vs. 30.0%, P=0.002) were significantly more common in coinfected patients. Compared to HCV monoinfected subjects, HIV/HCV coinfection was associated with a significantly increased odds of steatosis of any grade (OR=3.21; 95% CI, 1.84-5.60) and grade 2/3 steatosis (OR=5.63; 95% CI, 3.05-10.36) after adjusting for potential confounding variables. Among coinfected patients, the fibrosis progression rate increased in a linear fashion with the grade of steatosis. CONCLUSIONS: Steatosis is more common and more severe in HIV/HCV coinfected patients than in those with HCV monoinfection.     

Impact of chronic viral hepatitis on health-related quality of life in HIV: results from a nationally representative sample

BACKGROUND: Little is known about the health burden of chronic viral hepatitis in HIV-infected patients. We compared health-related quality of life (HRQOL) of patients with HIV and hepatitis C virus (HCV) or HIV and hepatitis B virus (HBV) coinfection to those with HIV monoinfection. METHODS: Using a nationally representative sample of 1,874 adults with HIV who completed a baseline and two follow-up interviews, we identified those with HIV monoinfection (n = 1,493), HIV-HCV coinfection (n = 279), and HIV-HBV coinfection (n = 122). We measured baseline and change over time scores for physical and mental health (PHS, MHS), overall quality of life (QOL), overall health, and disability days. To identify the independent effect of coinfection, we adjusted for demographic and clinical predictors of HRQOL using multivariable regression. RESULTS: Despite significant differences in socio-demographic characteristics between groups, there were no differences in the baseline scores for PHS, MHS, overall QOL, overall health, or disability days between groups. The HRQOL did not decline significantly over time for the HIV patients with or without HCV or HBV coinfection. All groups reported similar longitudinal changes in the HRQOL scores for all measures. CONCLUSIONS: We found no significant differences in disease burden as assessed by a generic HRQOL instrument between patients with HIV monoinfection and HIV-HCV or HIV-HBV coinfection. These data are relevant in counseling coinfected patients regarding the impact of coinfection on HRQOL, and are important in designing clinical trials and conducting cost-effectiveness analyses including this vulnerable cohort.     

Preservation of intrahepatic hepatitis C virus (HCV)-specific CD4+ T cell responses despite global loss of CD4+ T cells in HCV/HIV coinfection

BACKGROUND: Human immunodeficiency virus (HIV) coinfection and low peripheral blood CD4(+) T cell counts are associated with increased hepatitis C liver disease. METHODS: Hepatitis C virus (HCV)-specific CD4(+) T cell responses were assessed using interferon (IFN)- gamma enzyme-linked immunospot assays on peripheral blood mononuclear cells and expanded liver lymphocytes from HCV-monoinfected and HCV/HIV-coinfected subjects. Cell frequencies were determined using flow cytometry. RESULTS: HIV coinfection was associated with decreased CD4(+) T cell percentages in both peripheral blood (21% vs. 48%; P<.0001) and liver (15% vs. 36%; P<.0001) and with reduced responsiveness of peripheral CD4(+) T cells to HCV antigens compared with HCV monoinfection (22% vs. 45%; P=.021). However, intrahepatic HCV-specific responses were maintained in HCV/HIV coinfection, compared with HCV monoinfection (38% vs. 32%; P=.7). Notably, the presence of HCV-specific responses was not related to the frequency of liver CD4(+) T cells (P=.4). Circulating and liver CD4(+) T cell percentages were correlated (r=0.58; P<.0001). Circulating percentages were also inversely associated with liver fibrosis stage among HCV/HIV-coinfected subjects (P=.029). Neither hepatic CD4(+) T cell percentages nor HCV-specific IFN- gamma responses in the liver or periphery predicted stage. CONCLUSIONS: Despite decreases in peripheral blood HCV-specific CD4(+) T cell responses and intrahepatic CD4(+) T cell percentages, intrahepatic HCV-specific CD4(+) IFN- gamma responses were preserved in HCV/HIV coinfection.     

Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV‐positive patients

Patients infected with HIV are at increased risk for cardiovascular disease despite successful antiretroviral therapy. Likewise, chronic hepatitis C virus (HCV) infection is associated with extrahepatic complications, including cardiovascular disease. However the risk of cardiovascular disease has not been formally examined in HIV/HCV‐coinfected patients. A retrospective study was carried out to assess the influence of HCV coinfection on the risk of cardiovascular events in a large cohort of HIV‐infected patients recruited since year 2004. A composite event of cardiovascular disease was used as an endpoint, including myocardial infarction, angina pectoris, stroke or death due to any of them. A total of 1136 patients (567 HIV‐monoinfected, 70 HCV‐monoinfected and 499 HIV/HCV‐coinfected) were analysed. Mean age was 42.7 years, 79% were males, and 46% were former injection drug users. Over a mean follow‐up of 79.4 ± 21 months, 3 patients died due to cardiovascular disease, whereas 29 suffered a first episode of coronary ischaemia or stroke. HIV/HCV‐coinfected patients had a greater incidence of cardiovascular disease events and/or death than HIV‐monoinfected individuals (4% vs 1.2%, P = 0.004) and HCV‐monoinfected persons (4% vs 1.4%, P = 0.5). After adjusting for demographics, virological parameters and classical cardiovascular disease risk factors (smoking, hypertension, diabetes, high LDL cholesterol), both HIV/HCV coinfection (HR 2.91; CI 95%: 1.19–7.12; P = 0.02) and hypertension (HR 3.65; CI 95%: 1.34–9.94; P = 0.01) were independently associated with cardiovascular disease events and/or death in HIV‐infected patients. Chronic hepatitis C and hypertension are independently associated with increased cardiovascular disease risk in HIV‐infected patients. Therefore, treatment of chronic hepatitis C should be prioritized in HIV/HCV‐coinfected patients regardless of any liver fibrosis staging.     

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain

While hepatitis C virus (HCV) infection seems to be expanding among HIV‐infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV‐infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1–27.5) in 2004–2005 to 8.2% (95% CI, 6.9–9.5) in 2010–2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0–8.9%; and heterosexual women, 14.5–4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4–76.4), birth decade 1961–1970 (OR, 2.1; 95% CI, 1.1–3.7) and low educational level (OR, 2.4; 95% CI, 1.6–3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.     

Similar recovery of liver function after response to all‐oral HCV therapy in patients with cirrhosis with and without HIV coinfection

Among patients with cirrhosis, recovery of liver function after SVR to all‐oral direct‐acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV‐monoinfected and HIV/HCV‐coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR‐DAA and GEHEP‐MONO cohorts were selected if they had SVR12 to all‐oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child‐Pugh‐Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV‐infected individuals and in 82 (57%) HIV/HCV‐coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV‐monoinfected patients and in 33 (13%) HIV/HCV‐coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03‐4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004‐3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2‐5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3‐12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV‐monoinfected and HIV/HCV‐coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.     

HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy

Objectives

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).

Methods

Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.

Results

Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.

Conclusions

Coinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.

     

Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection

Objective

The aim was to examine the long‐term safety and efficacy of raltegravir in patients with HIV‐1 and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) coinfection in three double‐blind, randomized, controlled Phase III studies.

Methods

In STARTMRK, treatment‐naïve patients received raltegravir 400 mg twice a day (bid) or efavirenz 600 mg at bedtime, both with tenofovir/emtricitabine. In BENCHMRK‐1 and ‐2, highly treatment‐experienced patients with multi‐drug resistant virus and prior treatment failure received raltegravir 400 mg bid or placebo, both with optimized background therapy. Patients with chronic HBV and/or HCV coinfection were enrolled if baseline liver function tests were ≤5 times the upper limit of normal. HBV infection was defined as HBV surface antigen positivity for all studies; HCV infection was defined as HCV RNA positivity for STARTMRK and HCV antibody positivity for BENCHMRK.

Results

Hepatitis coinfection was present in 6% (34 of 563) of treatment‐naïve patients (4% HBV only, 2% HCV only and 0.2% HBV+HCV) and 16% (114 of 699) of treatment‐experienced patients (6% HBV only, 9% HCV only and 1% HBV+HCV). The incidence of drug‐related adverse events was similar in raltegravir recipients with and without hepatitis coinfection in both STARTMRK (50 vs. 47%) and BENCHMRK (34 vs. 38.5%). Grade 2–4 liver enzyme elevations were more frequent in coinfected vs. monoinfected patients, but were not different between the raltegravir and control groups. At week 96, the proportion of raltegravir recipients with HIV RNA <50 HIV‐1 RNA copies/mL was similar between coinfected and monoinfected patients (93 vs. 90% in STARTMRK; 63 vs. 61% in BENCHMRK).

Conclusion

Raltegravir was generally well tolerated and efficacious up to 96 weeks in HIV‐infected patients with HBV/HCV coinfection.     

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe

Objectives

The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV‐infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use.

Methods

Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti‐HCV) was collected retrospectively from the antenatal records of HIV‐infected women enrolled in the European Collaborative Study and linked to prospectively collected data.

Results

Of 1050 women, 4.9% [95% confidence interval (CI) 3.6–6.3] were HBsAg positive and 12.3% (95% CI 10.4–14.4) had anti‐HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV‐seropositivity prevalence (28%; 95% CI 22.8–35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86–4.58], age (for ≥35 years vs. <25 years, AOR 3.45; 95% CI 1.66–7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78–12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20–6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08–13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV‐seropositive than in HIV‐monoinfected women (AOR 0.34; 95% CI 0.20–0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log₁₀ HIV‐1 RNA copies/mL vs. HIV‐monoinfected women; P=0.03). HIV/HCV‐seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV‐monoinfected women (AOR 1.95; P=0.049).

Conclusions

Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.     

Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus

Summary. To evaluate, among 70 hepatitis C virus (HCV)‐monoinfected and 36 human immunodeficiency virus (HIV)‐coinfected naïve patients with genotypes 1/4 receiving weight‐adjusted pegylated interferon‐α‐2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV‐RNA decreases. HCV‐RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut‐off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV‐RNA (5·75 vs 5·72 log₁₀IU/ml, P = 0·6), HCV monoinfection led to significantly lower HCV‐RNA values at weeks 4 (3·7 vs 4·3 log₁₀IU/ml, P = 0·01), 12 (2·3 vs 3·5 log₁₀IU/ml, P = 0·01) and 24 (1·4 vs 3·3 log₁₀IU/ml, P = 0·001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0·02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV‐RNA decrease of at least 1 log₁₀ at week 4 was highly predictive of treatment failure for HCV‐monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0·86 [95% confidence interval (CI) 0·77–0·95], but not for HCV/HIV‐coinfected patients (cut‐off, 0 log₁₀, Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0·71 (95% CI 0·49–0·93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1·08–8.04, P = 0·01). Thus the magnitude of HCV‐RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut‐off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.