SEPTEMBER 1998

NUMBER ONE

Hepatitis Alert!
Liver Damage Is a Risk.

Viral hepatitis-with A, B, and C strains-poses a serious, overlooked problem for people with HIV, especially injection drug users and those on HAART therapy, say researchers who have sounded the alarm. A number of reports at the recent World AIDS Conference in Geneva showed that co-infection with hepatitis B and C can put individuals with HIV at very high risk for liver cirrhosis and liver cancer. Co-infection with hepatitis C can accelerate the progression of HIV disease, and the hepatitis C virus is not controlled by HAART. Similarly, some individuals have had hepatitis B flare-ups despite being on HAART. So far, because researchers have yet to figure out exactly how the immune system works against hepatitis viruses, even in HIV-negative people, these results aren't surprising. HAART therapy with protease inhibitors can also cause liver toxicity, and people with chronic hepatitis have been shown to have a higher risk of liver toxicity from HAART.

One Geneva report found signs of liver toxicity in about 14 percent (roughly one in seven) of people on HAART and this toxicity meant that about 6 percent (one in 17) had to stop the drugs. In some cases, liver damage can be fatal-in this study, a person who was co-infected with hepatitis B, C, and D died of liver failure after having started HAART. Studies of long-term survivors with HIV, especially those who used injection drugs, also show that chronic hepatitis remains a serious health risk.

Rates of hepatitis infection vary. Hepatitis B is prevalent among gay and bisexual men. Hepatitis A never becomes chronic, but acute hepatitis A infection is very dangerous in people with chronic HBV or HCV. In one alarming study in the New England Journal of Medicine, Italian researchers reported that individuals with chronic hepatitis C infection are at significant risk for fulminant hepatitis and death associated with hepatitis A superinfection. Hepatitis C is widespread in the general population and is estimated to affect at least 40 percent of people with HIV, with injection drug use being the most common route of transmission.

If you're HIV positive, it's important to get tested for hepatitis and find out if you need treatment. Be aware that HIV and HIV drugs can cause elevated liver enzymes and that hepatitis antibody tests aren't that sensitive. Most specialists now recommend using a quantitative PCR test for HCV if an antibody test comes back negative. Researchers can use a quantitative PCR that can detect hepatitis B.

People at risk for HIV should be vaccinated against hepatitis A and B, say experts; there is no vaccine for C. Some doctors now suggest individuals with chronic HCV be vaccinated for hepatitis A.

Treating chronic hepatitis can be difficult in those with HIV because standard therapies aren't that good-especially for hepatitis C (see "HIV Illnesses"). A Geneva report by German researchers showed that people with HIV and chronic HCV responded less well than HIV-negative people to the standard treatment with alpha interferon; IFN may also cause more neurotoxicity to HIV-positive people. Other IFN reports were more positive: A Spanish group found that long-term IFN treatment could control chronic HCV in co-infected individuals with HIV without severe immunodeficiency and should be recommended. In June, the FDA approved a combination of ribavirin and alpha interferon (called Rebetron) for HIV-negative people with chronic HCV who have failed IFN alone. Studies of Rebetron in people with HIV and HCV are ongoing. Another new drug by Amgen, called Infergen (Interferon alfacon-1), has been FDA-approved to treat chronic HCV.

Researchers in clinical trials are now testing combinations of nucleoside analog drugs that can lower viral load to below-detectable levels in chronic hepatitis B, but the virus can't be completely eradicated, say researchers. As with HIV, viral DNA remains latent in some cells. Also similar to HIV, antiviral monotherapy-using only one drug-can lead to drug resistance. Looking ahead, a study using of low-dose adefovir against HBV showed the drug completely eradicated the virus in the liver in early studies; adefovir may also have an immunomodulatory effect.

Several HBV drugs are being developed by Triangle Pharmaceuticals that also look good in early studies (FTC, DAPD/DXG, L-FMAU).