HIV Hepatitis C Virus Coinfection Research Articles

European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV‐infected adults

With the decline in HIV-associated morbidity and mortality following the introduction of highly active antiretroviral therapy (HAART), liver disease has emerged as a major cause of death in HIV/hepatitis B virus (HBV) and HIV/hepatitis C virus (HCV) coinfected persons. Therefore, screening for underlying viral hepatitis coinfection and the provision of management and treatment recommendations for patients with chronic viral hepatitis are of great importance in preventing, as far as possible, the development of liver disease. With the introduction of new agents for the treatment of hepatitis B and increased knowledge of how best to manage hepatitis C, an update of current guidelines for management of HBV and HCV coinfection with HIV is warranted. Clearly, all HIV-infected patients should be screened for hepatitis A, B and C, taking into account shared pathways of transmission. Patients who are seronegative for hepatitis A and B should be considered for vaccination. In HIV-infected patients with chronic hepatitis B, the first important differentiation is whether HAART is required or not. In the setting of stable HIV infection, with no need for HAART, several treatment options are available, namely treatment with interferon, early initiation of HAART, or selective non-HIV active anti-HBV nucleoside therapy, with the aim of achieving undetectable HBV DNA levels. In most cases, undetectable HBV DNA can only be achieved with combination therapy. With regard to hepatitis C, individualized tailoring of the duration of HCV therapy is advisable, taking into account rapid or delayed virological response. In patients who do not achieve at least a 2 log drop in HCV RNA at week 12, treatment can be terminated because of the low probability of achieving sustained virological response. Overall, with the currently available treatment algorithms, HCV can be eradicated in over 50% of patients. Therefore, HCV therapy should be considered and discussed with the patient if an indication for HCV therapy (elevated liver enzymes, positive HCV RNA and >F1 fibrosis) is present. Management of underlying hepatitis B and/or C in patients with HIV infection is of great importance in preventing liver disease-associated morbidity and mortality.

Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV–HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naïve patients with HCV-1a infection: (1) HIV–HCV positive ( n = 6); and (2) HIV negative–HCV positive ( n = 3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especially in those patients with CD4 < 200 cells/mm 3, who lost positive selective immune pressure in the HVR-1 region. Differences in immune regulation of HCV quasispecies in HIV coinfected individuals deserve further exploration to clarify the different outcomes of chronic hepatitis C noted between the immunocompromised and the immunocompetent host.

Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: A prospective, nonrandomized, crossover study in patients coinfected with hepatitis c and hiv receiving methadone maintenance treatment

Background: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. Objective: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. Methods: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged ≥18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40–200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone C max, T max, Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 μg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. Results: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean C max, T max, C min, AUC, and CL/F values despite 80% power to detect a 30% change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flulike symptoms. Conclusion: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.

Impact of Chronic Viral Hepatitis on Health-Related Quality of Life in HIV: Results from a Nationally Representative Sample

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. 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. 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. 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.

HCV chronic hepatitis in patients with HIV: clinical management issues.

HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.