|SPECIAL FEATURE||Vol.6 No.2 (April 2001)|
HIV and HBV Co-infection
Dr. Lai Sik-To, Thomas
Department of Medicine and Geriatrics, Princess Margaret Hospital
Hepatic abnormalities are not uncommon in HIV infected patients and these may be due to acute or chronic viral hepatitis. The risk factors for HIV and HBV infection are similar and the viruses may share the same routes of transmission. 80-90% of HIV positive patients are also positive for HBV markers. The state of HIV and HBV co-infection can arise either as a result of HIV infection of a case of chronic hepatitis B or HBV infection with evolution to chronicity in an HIV positive patient.
Both HIV and HBV have influence on the natural history of infection of one another. Approximately 20% of HIV infected persons who acquire acute HBV infection develop chronic hepatitis compared with only 5% of HIV negative persons. Spontaneous reactivation of HBV replication has been reported in patients with stable chronic hepatitis B or anti-HBs positive patients who develop immunosuppression due to HIV infection. There is accelerated loss of naturally acquired anti-HBs among immunodeficient homosexual men infected with HIV.
In contrast to previous studies, HIV does not attenuate and may even worsen HBV-related chronic liver damage. Lethal liver failure may develop before the appearance of any complication of HIV infection. While one study concluded that chronic HBV infection did not appear to influence the HIV disease progression, another later study found that chronic HBV infection may accelerate the course of HIV infection.
In the past, there has been a reluctance to treat patients who are co-infected with HIV and HBV. However, Hong Kong is witnessing a steady increase in the number of HIV-infected patients over the years. Improved survival in these patients has led to a heightened interest in the treatment of the underlying hepatitis B.
Alpha-interferon has all along been the only approved agent for chronic hepatitis B in Hong Kong until lamivudine was registered for this indication in December 1998. The standard dosage of alpha-interferon is 5-10 million units thrice a week given subcutaneously for 4-6 months.
Although responses of HBV to interferon have been described in early HIV/HBV co-infection, there does not seem to be a reliable way of distinguishing asymptomatic patients who are likely to respond to treatment. A lack of correlation between the response to treatment and the pre-treatment CD4 cell count and p24 antigenaemia has been described.
Treatment should be considered in all categories of patients, including HIV-infected, who have persistent elevation of alanine aminotransferase, detectable levels of HBsAg, HBeAg and HBV DNA in serum, active inflammation on liver biopsy and compensated liver disease. 33% of patients with the above characteristics will respond. In one study, 45 patients with and without HIV infection had the percentages of seroconversion to anti-HBe remained stable (same for treatment and placebo) for 4-9 years after completion of a 12-week trial of alpha-interferon.
There is diminished responsiveness of male homosexual chronic hepatitis B carriers with positive HIV antibody to interferon therapy. This may be due to subclinical immunosuppression effects of co-infection with HIV.
Lamivudine is effective in producing HBeAg seroconversion and reducing fibrosis in chronic hepatitis B with little toxicity. Treatment of patients who were co-infected with HIV and HBV showed significant reduction in HBV DNA concentration. In 118 HIV positive patients with HBsAg positivity, lamivudine 150 mg bd was added to other NRTIs. The HBV DNA dropped by 2.7 log after one year and nearly 50% became HBV DNA negative and the ALT was normalised in 50%.
Another study of the effect of lamivudine (150 mg/12 h), indinavir (800 mg/8 h) and zidovudine (300 mg/12 h) or stavudine (30-40 mg/12 h) in 17 patients with chronic HIV and HBV infection showed that HBV-DNA was suppressed in most patients and ALT values significantly decreased throughout the trial. HBeAg seroconversion was obtained in 29% of patients after 12 months of therapy. This is a higher rate than the 20% reported in other series of HIV-negative patients. The use of two nucleoside analogues, a higher dose of lamivudine and the addition of a protease inhibitor could have contributed to more efficient suppression of HBV replication through the improvement of the immune response.
At present, lamivudine is the drug of choice by default since many patients are already taking lamivudine-containing combination therapy. Resistance to lamviudine develops during treatment. With the emergence of the YMDD mutant of HBV, patients will continue to receive lamivudine in most clinical studies. It should be noted that both resistance to and withdrawal of lamivudine may result in flare of hepatitis. In patients who are intolerant of lamivudine or whose HIV develops lamivudine resistance, alpha-interferon may be used to treat the HBV infection.
The older antivirals like famciclovir and ganciclovir can cause a reduction in the HBV DNA and ALT levels but they are rather weak agents. The newer antivirals for AIDS, like adefovir, are more potent inhibitors of HBV and may be employed for simultaneous treatment of HIV and HBV co-infection in the future.
HIV-infected patients who are considered candidates for hepatitis B vaccination (injection drug use, sexually active gay men, heterosexual men and women with sexually transmitted diseases or more than one sex partner in the past six months, and household or sex contact of an HBsAg carrier) should have serological testing to determine established immunity using anti-HBc. HBV vaccination is offered to those who belong to the above risk groups and are negative for anti-HBc.
Studies of acute HBV infection in patients with or without HIV infection show no differences in clinical features or biochemical changes, but the risk of becoming a chronic carrier of HBsAg is 10-37% in HIV infected patients compared to 6% in those without HIV infection. Based on these findings, some authorities have argued for more liberal use of HBV vaccine in HIV-infected patients who are susceptible (seronegative).
The regime of hepatitis B vaccination is 3 intramuscular doses at 0, 1, and 6 months using HB-Vax II 10 mg or Engerix B 20 mg. The response rates are substantially decreased in persons with HIV infection. In a study of hepatitis B vaccination in HIV positive homosexual men, anti-HBs only appeared in 42.9% (6 in 14). The response to hepatitis B vaccination has been found to be related to the CD4 lymphocyte cell count. The seroconversion rates were found to be 33.3%, 55% and 87.5% in patients with CD4 lymphocyte cell count of <200/µl, 200-500 µl and >500/µl respectively.
The CDC recommends post-vaccination serology for anti-HBs at 1-6 months after the third dose in patients with HIV infection to confirm an antigen response. Non-responders should receive 1-3 boosters, a tactic that produces serological response in 30-50% of healthy adult non-responders. There is evidence that increasing the number of HBV vaccine injections augments the anti-HBs response rate in HIV infected patients.
Concern has been raised pertaining to hepatitis B vaccination may potentially increase the HIV load, analogous to the situation seen in some HIV infected patients who have received influenza vaccination. However, hepatitis B vaccination has been shown to have limited effect on HIV viral load and one report noted that there was little increase in the HIV load after immunisation with HBV vaccine in patients with moderate to severe immunodeficiency.
In conclusion, hepatitis B vaccination is indicated for all susceptible HIV-infected persons. According to the USPHS/IDSA guidelines (1995), this recommendation belongs to the BII category in strength and quality.