The management of HIV and hepatitis B coinfection

PURPOSE OF REVIEW: Coinfection with HIV and hepatitis B virus has a significant impact on the natural history of hepatitis B disease with faster rates of progression to cirrhosis and end stage liver disease. An increasing number of hepatitis B virus active drugs are now available, many of which have dual anti-HIV activity. This review highlights the most important recent developments in the management of HIV and hepatitis B virus coinfection. RECENT FINDINGS: Natural history studies continue to confirm the increased rate of liver-related mortality in coinfected individuals and the importance of hepatocellular carcinoma in this population. The most recent studies of adefovir and tenofovir in open label use in coinfected individuals are discussed and new data on the activity of emtricitabine, entecavir and pegylated interferon are presented. Strategies for use of these new options for anti-hepatitis B virus therapy in coinfected individuals are discussed. SUMMARY: Prevention of end stage liver disease and hepatocellular carcinoma in the coinfected population is vital and the increasing availability of drugs with potent anti-hepatitis B activity is encouraging. Appropriate diagnosis and monitoring of hepatitis B, coupled with better understanding of the mechanisms of drug resistance, will enable clinicians to manage coinfection more effectively.     

Understanding the pathogenesis and management of hepatitis B/HIV and hepatitis B/hepatitis C virus coinfection

The approach to the hepatitis B virus (HBV)-infected patient who is also infected with HIV or hepatitis C virus (HCV) is very different from the approach to the patient with only one virus infection. HBV/HIV coinfection is common. Agents that have dual activity against HBV and HIV should be considered as treatment of choice in combination regimens in HBV/HIV-coinfected patients beginning antiretroviral therapy. In HBV/HCV coinfection HCV usually tends to predominate over HBV. More investigation is needed into the mechanisms by which viral pathogenesis is altered and the optimal treatment modalities for coinfected patients.     

Current treatment of HIV/hepatitis B virus coinfection

Coinfection with HIV and hepatitis B virus (HBV) has become a significant global health problem. Liver disease is now one of the leading causes of morbidity and mortality in individuals with HIV, particularly those with viral hepatitis. There are a number of agents available with dual activity against HIV and HBV, and effective treatment depends on understanding the potential advantages and pitfalls in using these agents. There are a number of unresolved issues in the management of HIV/HBV coinfection. These include the role of liver biopsy, the significance of normal aminotransferase levels, serum HBV DNA threshold for treatment, treatment end-points, and the treatment of HBV when HIV does not yet require treatment. Treatment of HBV should be considered in individuals with HIV/HBV coinfection with evidence of significant fibrosis (>/=F2), or with elevated serum HBV DNA levels (>2000 IU/mL). Sustained suppression of serum HBV DNA to below the level of detection by the most sensitive available assay should be the goal of therapy, and, at present, treatment of HBV in HIV/HBV coinfection is lifelong. If antiretroviral therapy is required, then two agents with anti-HBV activity should be incorporated into the regimen. If antiretroviral therapy is not required, then the options are pegylated interferon, adefovir or the early introduction of antiretroviral therapy. Close monitoring is necessary to detect treatment failure or hepatic flares, such as immune reconstitution disease. Further studies of newer anti-HBV agents in individuals HIV/HBV coinfection may advance treatment of this important condition.     

HIV and hepatitis B virus: options for managing coinfection

At the International AIDS Society-USA course in New York in October 2002, Douglas T. Dieterich, MD, presented the case history of a patient coinfected with HIV and hepatitis B virus (HBV). HBV infection in patients with HIV is associated with worse prognosis for HBV disease than in patients without HIV and complicates management of both diseases. However, newer treatment options for chronic HBV infection increase the potential for successful management.     

HIV and hepatitis C virus coinfection update

Sharing routes of transmission, hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are often harbored in the same host, establishing chronic infections characterized by high serum viral loads. HIV-1 impacts the course of HCV infection by increasing the rate of HCV viral persistence, quantitative viral loads, and liver fibrosis progression rate. HCV in turn affects HIV management, particularly by increasing the risk of hepatotoxicity. Future studies will focus on understanding the pathogenesis of accelerated liver fibrosis in HIV-infected individuals, the natural history of HCV in the era of antiretroviral therapy, and the principles of managing these two infections within the same individual.     

Hepatitis C virus in the setting of HIV or hepatitis B virus coinfection

Because of shared routes of transmission, coinfection with hepatitis C virus (HCV) or hepatitis B virus (HBV), or both, is common among HIV-infected persons, affecting approximately 15 to 30% and 10 to 15% of patients, respectively. Advances in antiretroviral therapy have improved the life expectancy of patients infected with HIV, and, as a consequence, HCV-related liver disease has emerged as a significant comorbid disease among such patients. Concurrent HIV infection may be associated with higher serum HCV RNA levels, accelerated progression of hepatic fibrosis, increased risk of end-stage liver disease, hepatocellular carcinoma and death among persons coinfected with hepatitis C. Similarly, coinfection with HCV and HBV may lead to more severe liver disease and greater risk of hepatocellular carcinoma (HCC) than does HCV infection alone. Although definitive randomized controlled trials are not yet completed, current guidelines recommend the use of pegylated interferon alfa plus ribavirin for the treatment of chronic HCV in eligible HIV-infected persons. Conversely, the optimal treatment of chronic HCV in persons with chronic HBV infection has not been defined but may include pegylated interferon alfa plus ribavirin, with or without additional antiviral agents, such as lamivudine or adefovir, or both.     

Prevalence and correlates of HIV and hepatitis B virus coinfection in Northern Alberta

BACKGROUND:

HIV and hepatitis B virus (HBV) share transmission routes, and coinfection is associated with higher morbidity and mortality. To date, no Canadian studies have examined HIV-HBV coinfection.

OBJECTIVES:

To examine the prevalence and correlates of HIV and HBV coinfections in Northern Alberta.

METHODS:

The present study was a retrospective database review of all HIV-infected (HIV+) individuals in Northern Alberta from 1982 to 2010 and a chart review of HBV surface antigen-positive individuals for whom charts were available (46.2%).

RESULTS:

Of 2844 HIV+ patients, 2579 (90.7%) had been tested for HBV surface antigen, and 143 (5.5%) of these were HBV coinfected. Coinfected males were primarily Caucasian (70.8%), and coinfected females were primarily black (56.4%) or Aboriginal (31.3%). Coinfected individuals were more likely to be male (88.1% versus 71.3%; P<0.001) and to have died (34.3% versus 17.9%; P<0.001).

CONCLUSIONS:

The prevalence of coinfection with HBV in HIV-infected patients in Northern Alberta is lower than reported in other developed nations. The pattern of coinfections in Northern Alberta likely follows immigration trends. Recognition and management may be improving with time; however, further research and additional strategies are required to enhance the prevention, identification and management of HBV infection in HIV-infected individuals.     

HIV, hepatitis B and hepatitis C coinfection in Kenya

There are few data regarding hepatitis and HIV coinfection in Africa. In 378 HIV seropositive individuals in Nairobi, 23 (6%) were hepatitis B virus (HBV) and HIV coinfected, four (1%) were hepatitis C virus (HCV) and HIV coinfected and one patient was infected with all three viruses. Coinfected individuals were more likely to be men and older; a lack of HBV vaccination was a risk factor for HIV/HBV coinfection (P = 0.001) and tenofovir containing regimens appeared most effective at reducing HBV viral load.     

Treatment of hepatitis C virus/HIV coinfection

Coinfection with HIV and hepatitis C virus (HCV) has grown in importance and clinical impact in recent years. This change is attributable to the increase in life expectancy of those living with HIV infection since the advent of highly active antiretroviral therapy. This article reviews treatment options for patients who are coinfected with HIV and HCV.     

HIV and hepatitis C virus coinfection: bad bedfellows

Hepatitis C virus (HCV) infection is common in HIV-infected individuals and is responsible for increasing morbidity in these patients. HIV infection increases HCV replication and accelerates progression of HCV disease. HCV infection increases the risk of antiretroviral treatment. HCV genotype 1 is the predominant genotype in HCV/HIV-coinfected individuals living in the United States. State-of-the-art treatment with peginterferon alfa plus ribavirin results in lower sustained HCV virologic response rates in patients with genotype 1 infection than in those infected with other genotypes. Data from studies of HCV infection treatment in coinfected patients are discussed, as are prospects for future therapy. This article summarizes a presentation on HIV/HCV coinfection by Robert T. Schooley, MD, at the International AIDS Society-USA course in San Francisco in June 2005.     

Update on hepatitis B and C coinfection in HIV

Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is common in patients with HIV infection. HIV infection and immunosuppression alter the natural history of chronic viral hepatitis, and some patients experience accelerated progression to clinically significant liver disease. Therapies used in the treatment of HBV or HCV monoinfection have been applied to the treatment of HIV-coinfected patients. However, development of viral resistance and lack of virologic response remain significant areas of concern. Timely diagnosis and clinical staging of chronic hepatitis infection are critical in the management of HIV-coinfected patients.     

Hepatitis B virus replication in hepatitis B and D coinfection

The clinical course, changes in liver function tests and the behaviour of viral markers over the course of time have been examined in 45 patients with acute hepatitis B and 14 patients with acute hepatitis caused by B and D viruses coinfection. There were no significant differences either in the clinical course or in the liver function tests, in the two groups. The changes in serum viral markers were as follows: HBV-DNA was the first marker to disappear; this was closely followed by HBeAg, and HBsAg was the last marker to become negative, during convalescence. This pattern was not altered by Delta coinfection. When we quantified serum HBV-DNA in both groups of patients, we found that Delta virus infection led to parital inhibition of HBV replication, so that serum HBV-DNA levels were significantly lower in those patients with acute hepatitis B who were simultaneously infected with Delta virus.     

Vertically acquired paediatric coinfection with HIV and hepatitis C virus

Both HIV and hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and delivery. Vertical transmission of HIV and HCV separately is most likely from HIV/HCV-coinfected mothers; however, transmission of both infections is less frequent. The effect of HCV coinfection on HIV-related disease remains unclear; whereas most studies indicate no effect, recent results suggest HCV in adults accelerates HIV progression. Little is known about how HIV coinfection affects HCV progression in children and the information available is based on small numbers of patients. Paediatric HIV treatment is extremely successful and it is vital to determine if HCV coinfection alters the effectiveness of this treatment. The hepatotoxicity of many HIV therapies and the possible negative impact of HCV on this treatment, alongside the interactions and contraindications of many HIV and HCV therapies, further limits the choice of paediatric treatments for coinfected children. Future research must therefore focus on vertically acquired HIV/HCV coinfection to inform treatment trials addressing coinfection management.     

HIV and hepatitis C coinfection

Coinfection with HIV and the hepatitis C virus (HCV) or hepatitis B virus (HBV) is a growing public health concern. Because the diseases are spread in similar ways--notably through shared use of needles to inject drugs and sexual activity--many people are coinfected with HIV and HCV, HIV and HBV, or even all three viruses. Hepatitis C and hepatitis B are viral infections of the liver; over time they can lead to serious consequences including liver cirrhosis and liver cancer. Most studies show that HIV infection leads to more aggressive hepatitis C or hepatitis B and a higher risk of liver damage. Studies of how HCV and HBV affect HIV disease are less clear. Most research shows that HCV does not accelerate HIV disease progression, but HIV/HCV coinfection may impair immune system recovery after starting antiretroviral therapy. Coinfection can complicate treatment. People with liver damage due to chronic hepatitis are more likely to experience hepatotoxicity (liver toxicity) related to anti-HIV drugs. In addition, drugs used to treat HIV and hepatitis can interact and side effects may be exacerbated. Most experts recommend that HIV should be controlled first before a person begins HCV treatment. With careful management, most people with HIV/HCV or HIV/HBV coinfection can be successfully treated for both diseases. In fact, several recent studies suggest that HIV/HCV-coinfected people with well-controlled HIV disease and relatively high CD4 cell counts may do as well as those with HCV alone.