HBV/HIV Coinfection: What You Need to Know

Christine M. Kukka
HBV Project Manager;

Liver damage from hepatitis B is one of the most important medical issues facing HIV positive individuals. In the United States, nearly 1 million people are infected with HIV, and an estimated 10 percent of them are also infected with the hepatitis B virus (HBV). HIV-infected people are three to six times more likely to develop a chronic or long-term hepatitis B infection because of their weakened immune systems than individuals without HIV.

Despite advances made in the treatment of HIV, liver disease from hepatitis B continues to cause serious health problems in the HIV-infected. People coinfected with both hepatitis B and HIV are 14 to 17 times more likely to die than those with hepatitis B alone. Those coinfected with HIV and HBV also face accelerated liver scarring or cirrhosis. To make matters worse, some medicines used to treat HIV are toxic to the liver, which may already be damaged from the hepatitis B infection.

Hepatitis B is transmitted the same way HIV is. Oral, vaginal and anal sex transmit HBV as does exposure to infected blood through reused syringes or even cocaine straws. Hepatitis B is 100-times more transmissible than HIV because of the high “viral load” in HBV-infected blood and body fluids. Unlike HIV, HBV is a hearty virus that can survive for days in dried blood.

Unfortunately, despite the availability of a safe and effective vaccine that prevents hepatitis B, many teens and adults have not been immunized. One study found only 14 percent of HIV-positive people had been vaccinated against HBV.

While coinfection with HIV and hepatitis B remains poorly understood, today more information and new drugs are emerging that can help prevent liver damage in those infected with HIV and hepatitis B.

HIV: The Basics

The human immunodeficiency virus (HIV) is an RNA virus that causes acquired immunodeficiency syndrome (AIDS). HIV primarily infects white blood cells called CD4 lymphocytes, which help the body fight infections. HIV enters the cell and integrates into the DNA. HIV uses the cell to produce more HIV and this eventually kills the host CD4 cell.

While HBV is a DNA virus, it behaves the same way as HIV. Hepatitis B viruses integrate into liver cells to produce more HBV.

Eventually, HIV overwhelms the immune system, causing so many CD4 cells to die that the body’s immune system can no longer fight infections. This, in turn, leads to the development of opportunistic illnesses, such as Pneumocystis carinii pneumonia (PCP). And, as the immune system weakens, it can no longer fight the hepatitis B infection in the liver.

Transmission
HIV, like HBV, is transmitted by infected body fluids, including blood, semen, and vaginal secretions. It can also be transmitted from mother to child at birth or through breast milk. It is commonly spread by sexual contact and sharing HIV-infected needles or syringes.

Diagnosis
Two tests are used to establish HIV infection. The enzyme-linked immunosorbent assay (ELISA) tests for antibodies. If this test is positive, a confirming test, called a Western blot test, is done. Note that there is a six-week to six-month window period before the body develops antibodies against HIV. Viral load testing (by PCR or bDNA test looking directly for the virus) is not used to diagnose HIV, but is used to monitor HIV activity in the body after diagnosis is established by the antibody test.

Monitoring HIV disease progression
The viral load test measures the amount of virus circulating in the blood. The CD4 cell count measures the health of the immune system itself. Normal CD4 count is 500-1200. These two tests, viral load and CD4 count, are the standard tests used; they are normally done every three months. Increasing viral loads and/or decreasing CD4 counts generally mean that HIV disease is progressing.

HIV Treatment

Antiretroviral Treatment
Effective treatment for HIV requires a combination of at least three drugs. The best time to start treatment with HIV antiretroviral medication is controversial. Some medical authorities believe starting antiviral therapy soon after testing positive for HIV will help the body fight HIV. However, many practitioners prefer to wait until HIV viral load is between 30,000-50,000 copies, or the CD 4 count is between 300-400 before starting therapy. Antiretroviral medications include:

• Nucleoside Reverse Transcriptase Inhibitors (NRTIs):

Examples are AZT (Retrovir), d4T (Zerit), ddI (Videx). Lamivudine (Epivir or 3TC) is an anti-HIV treatment in this class of drugs that breaks down into chemicals that stop HIV from infecting uninfected cells in the body. About 80 percent of HIV-positive patients are treated with lamivudine. Interestingly, lamivudine is also used to treat hepatitis B infections. As with HIV, this drug also interferes with the hepatitis B virus’s DNA so it cannot replicate effectively. Unfortunately, there are some HBV that are able to develop a resistance to lamivudine’s antiviral punch over time, so this drug loses its ability to control HBV replication after two to four years.

• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs):

Examples are efavirenz (Sustiva), nevirapine (Viramune).

• Protease Inhibitors (PIs):

Examples are ritonavir (Norvir), indinavir (Crixivan).

• Entry inhibitors:

An example is entuvirtide (Fuzeon).

Many of these medications can have serious side effects including fatigue, fevers, headaches, rashes, depression and more. Because the liver metabolizes these drugs, it is extremely important that coinfected people are monitored for potential liver toxicity and exacerbation of HBV-related liver disease.

Opportunistic Illnesses: Prevention and Treatment
When CD4 counts drop below 200 a person is susceptible to a variety of opportunistic infections and people with HIV will be given medications to treat or prevent these infections.

HIV/HBV Coinfection

HIV, if left untreated, can lead to serious complications and death. Hepatitis B, however, is usually a slowly progressive disease that can take years or decades to cause serious liver damage. About 15 to 25 percent of people infected with just hepatitis B will develop and die from liver disease, such as cirrhosis and liver cancer. People coinfected with HIV and hepatitis B may have a more rapid progression of liver disease due to their weakened immune systems, and the addition of medications that can be toxic to their HBV-infected livers.

Treating HIV in the HBV-positive individual
The good news is that HIV can be successfully treated in people co-infected with HIV and hepatitis B. However, because some HIV medications may be toxic to the liver, both an HIV specialist and a liver specialist (a gastroenterologist or hepatologist) should collaborate when treating coinfected people.

Drugs that have been associated with liver toxicity include:

Nucleoside Reverse Transcriptase Inhibitors (NRTIs): AZT (Retrovir) has been found to produce some liver toxicity, especially at high doses; people taking it should be monitored. Other NRTIs, including ddI (Videx), d4T (Zerit), ddC (Hivid), and abacavir (Ziagen) have been known to produce liver problems as well.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Nevirapine (Viramune) can produce drug-induced liver abnormalities, including hepatitis, in 8% - 28% of patients. Some individuals using efavirenz (Sustiva) have developed elevated liver enzymes.

Protease Inhibitors (PIs):
HIV PIs are generally the hardest on the liver and merit the closest attention. However, the majority of these medications can be well tolerated. Ritonavir (Norvir) appears to produce the majority of liver related toxicity. Indinavir (Crixivan) has also been associated with liver toxicity. Saquinavir (Fortovase) is much less toxic but the combination of saquinavir and ritonavir increases the potential for liver damage. Severe liver toxicity with nelfinavir (Viracept) is rare. Potential for liver toxicity with amprenavir (Agenerease) is not well-established, but people with impaired liver function may require lower doses of amprenavir.
The newest PI, Kaletra, combines lopinavir with ritonavir, and is known to elevate liver enzymes. Because PI’s are increasingly given with small doses of ritonavir, liver function needs to be frequently monitored. The potential for HIV medications to produce liver damage is very real. HIV medications may increase liver enzyme levels and HBV viral load, but these will usually stabilize over time.

Treating Hepatitis B in the HIV Positive Individual

There are three antiviral medications available to treat coinfected individuals.

Lamivudine: As noted, lamivudine has been effective in coinfected patients; it has significantly reduced HBV DNA. However, lamivudine-resistant hepatitis B viruses appear more quickly in coinfected patients than in those with just hepatitis B, reaching 90 percent at four years.

Adefovir (Hepsera): Adefovir, at 10 mg per day, has been effective in coinfected patients with lamivudine-resistant hepatitis B, resulting in a four-log decrease in HBV DNA levels and normalization of liver enzymes or ALT (which increase when liver cells are damaged or die) after 48 weeks of treatment. No adefovir-resistant hepatitis B viruses have developed. Because adefovir at the 10-mg dose is not effective against HIV, it appears that at this dosage HIV will not develop resistance to adefovir.

Tenofovir (Viread): Several studies have found that the antiviral tenofovir is effective against both HIV and HBV. One study showed that treatment with tenofovir resulted in 0.6-log decrease in HIV level and a five-log decrease from baseline for HBV level. Similarly, another coinfection study showed a four-log decrease in HBV DNA level by week 24 and an increase in CD4 cells. However, there have been reports of renal toxicity and hypophosphatemia associated with tenofovir therapy. Clinical trials exploring the safety and effectiveness of tenofovir to treat people coinfected with HIV and hepatitis B are continuing.

Treatment recommendations:
Therapy for HIV/HBV coinfected patients must be designed carefully for each individual, based on the condition of his/her immune system and liver. Currently, tenofovir and adefovir appear equally potent against hepatitis B, but adefovir is ineffective against HIV at the 10-mg dose prescribed for hepatitis B.

• If a patient’s HIV infection is not being treated, the patient should not be treated with tenofovir or lamivudine, because they can act against HIV. Adefovir at the 10 mg monotherapy dose is an option because it will treat hepatitis B, but have no impact on HIV. Tenofovir or lamivudine monotherapy is not recommended at this stage because of the risk for development of drug-resistant HIV.
• If a patient is being treated for HIV infection, a highly active antiretroviral therapy regimen containing tenofovir or a tenofovir and lamivudine combination is an option. For patients who are on a stable HIV treatment regimen, it may be preferable to add adefovir, rather than switch to tenofovir, to cover both viruses.

For more treatment recommendations see:

A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States.

Read the section on treatment of HIV-HBV coinfected patients.

Back to Hepatitis B