The
Double Challenge of HIV/HCV
Co-infection:
An Update
What clinical parameters should be followed to allow interferon
treatment of the Hepatitis C patient with significant liver disease who is
also co-infected with HIV?
Geoffrey L. Braden, MD --
Response
HIV and HCV
Co-Infection
HBV/HIV Co-infection
Posted April 11, 2003
Liz Highleyman
A great deal of attention has focused recently on co-infection with
Hepatitis C virus (HCV) and HIV. But co-infection with
Hepatitis B virus (HBV) and HIV is also an important public health issue.
Co-infection refers to infection with more than one disease-causing
organism. HIV, HBV, and HCV are spread in similar ways, and many people are infected with two or even all three of these viruses. All may be transmitted through blood-to-blood contact (for example, sharing used needles), but HIV and HBV
are more likely than HCV to be transmitted through sex or from mother to child during pregnancy or birth. Studies show that sexual and perinatal HBV transmission are more likely if a person also has HIV. Experts increasingly recommend that people with HIV should be screened for both HBV and HCV.
Like HCV, HBV can cause serious liver disease-including cirrhosis and liver cancer-usually after many years. Most people with healthy immune systems are able to clear HBV. Only about 5% of HBV-infected adults develop chronic
Hepatitis B; the rate is higher-about 90%-among those infected as infants. People co-infected with HIV, however, are 3-6 times more likely to develop
chronic
Hepatitis than those with HBV alone. In addition, HBV genetic material remains in human cells and the virus may reactivate as immune function deteriorates.
Much remains unknown about HBV/HIV co-infection, and study results are sometimes conflicting. Studies have shown that liver damage is more common and more severe and
Hepatitis B disease progression is more rapid in HBV/HIV-co-infected people than in those with HBV alone. Some researchers have shown that the risk of death due to liver complications is increased in HBV/HIV-co-infected people, although others have not found this to be the
case. On the other hand, most research indicates that HBV does not appear to adversely affect HIV disease progression. For example, Dr. Andrea de Luca and colleagues reported in the October 14, 2002 issue of the Archives of Internal Medicine that co-infection with HBV did not increase the risk of AIDS-defining illnesses or death. In one small study presented at a recent medical conference, HBV co-infection was actually associated with reduced
HIV
replication.
Many people with chronic Hepatitis B do not need treatment. Most doctors recommend against treatment for people who have low HBV viral loads, normal ALT levels, and minimal liver damage as determined by liver biopsy. HIV co-infection should not be regarded as a contraindication to HBV therapy. People with active, replicating HBV-including those with HIV-should be
considered for treatment. Three drugs are currently approved to treat
Hepatitis B: standard interferon, 3TC (lamivudine or Epivir), and adefovir (Hepsera, just approved this past September); pegylated interferon and tenofovir (Viread) are under study, and results so far look promising.
Unlike HCV drugs, some medications used to treat HBV-notably 3TC, adefovir, and tenofovir-are also active against HIV. Coinfected people who take 3TC as part of their HIV treatment regimen typically have lower HBV viral loads. However, use of 3TC usually leads to the development of drug-resistant HBV.
Adefovir was originally developed as an HIV treatment (under the brand name Preveon), but was never approved because it caused kidney toxicity; Hepsera for HBV is used in lower doses (about one-tenth as much) and is safe. Tenofovir is already approved to treat HIV.
Several studies presented at recent conferences have shown that adefovir and tenofovir are effective treatments for people with HBV/HIV co-infection. The drugs appear active against both wild-type (non-mutated) and 3TC-resistant HBV. For example, at the 2002 International AIDS Conference, Dr. Yves Benhamou and colleagues presented data showing that HBV viral load decreased
in HBV/HIV-co-infected people after they added adefovir to their existing
HIV drug regimens; about one-quarter (9 out of 35) achieved an undetectable HBV viral load and 3 out of 35 became negative for HBe antigen. ALT levels also decreased, and among those who had repeat liver biopsies over half showed reduced liver tissue damage. Even more promising, Mark Nelson and colleagues
reported at a conference last September that over half of the 18 HBV/HIV co-infected
people in their study achieved undetectable HBV viral loads when tenofovir
was added to their HIV drug regimens. Both adefovoir and tenofovir appear to
be well tolerated, with few people discontinuing treatment due to side
effects.
Co-infection with HBV can complicate HIV treatment. Many HIV drugs are metabolized by the liver, and people with existing liver damage due to chronic
Hepatitis are more likely to develop drug-related hepatotoxicity (liver toxicity, indicated by elevated liver enzyme levels). For example, Dr. Mark Sulkowski and colleagues reported in the January 2002 issue of Hepatology that over two-thirds of the cases of severe liver toxicity due to HIV drugs in their study were seen in people co-infected with HBV or HCV.
Among the HIV drugs, nevirapine (Viramune) and ritonavir (Norvir) are most often associated with liver toxicity. In addition, some HIV drugs can cause side effects similar to those of HBV drugs; for example, both interferon and AZT can cause low white blood cell counts. When these drugs are used together, worse side effects can result. Finally, much of the liver damage associated with
Hepatitis B is due to the immune system's response to the
virus, rather than the activity of HBV itself. Starting HIV treatment can sometimes cause liver enzyme "flares" in people with HBV as the
HIV drugs promote immune recovery.
Whenever possible, the care of people with HBV/HIV co-infection should be managed by a doctor who has experience with both diseases, or a team that includes both a hepatologist (liver disease specialist) and an infectious disease expert. Given the promising results of recent drug trials, use of 3TC together with adefovir or tenofovir should lead to less drug-resistant HBV and better treatment outcomes for HBV/HIV-co-infected people. With
careful monitoring, most people with
Hepatitis B and HIV can be successfully treated for both diseases.
Copyright February 2003 - Hepatitis C Support Project - All Rights Reserved. Permission to reprint is granted and encouraged with credit to the Hepatitis C Support Project