Evidence shows hepatitis C virus is playing major role in AIDS deaths
HIV treatment may have to follow Hep C cure
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An ICAAC study from Madrid, Spain, showed a strong association between HIV and HCV infection, with 30.5% of 446 HCV-infected patients having HIV infection.1 Hepatitis C is ubiquitous in injection drug users (IDUs), with 80% of the IDUs who are infected with HIV also having HCV, Klein says. "Anywhere from 70% to 90% will have active infection," Klein adds. "Most injection drug users will be exposed to hepatitis C, and most of those will have persistent infection, and the rates vary from study to study." Hepatitis B also is a problem among HIV-infected people, but because a smaller percentage of people infected with hepatitis B have chronic liver problems, it is not as serious a coinfection, Klein says.
Routine HCV vaccinations advised
HIV patients should be tested for hepatitis B, and if they have not been exposed, it would be a good idea to offer them the routine vaccination that is available to everyone who is sexually active, Klein says. "If people are not already immune, they should have the vaccine," Klein says. "It’s a question of relative risk, and the more sexually active, the greater the risk."
While hepatitis infections among HIV-infected patients are among the most serious of complications, the fact remains that HIV-infected drug users often die from causes that are the result of the same behaviors that led to their becoming infected with HIV, such as drug overdoses, says Dawn K. Smith, MD, MS, MPH, a medical epidemiologist with the Division of HIV/AIDS Prevention at the Centers for Disease Control and Prevention in Atlanta.
In the HER study, in which researchers followed HIV infection in women from 1993 to 1999, investigators found that when HAART use increased, the incidence of opportunistic infections and HIV-related deaths declined. At the same time, there was an increase in the number of deaths related to hepatitis, endocarditis, and sepsis, all of which are associated with injection drug use, Smith says. "I think the basic point to be made is that as we have gotten better at treating the underlying immune compromise through use of HAART and the use of antibacterial prophylaxis regimens, we’ve been able to significantly impact death rates that are not attributable to HIV infection," Smith says. "But the deaths related to underlying conditions in people’s lives obviously are not treated by those HIV-specific therapies, so they are taking on an increasing role in the deaths of HIV-infected patients," she continues.
New research demonstrates that patients who have a coinfection of HIV and HCV have higher tumor necrosis factor-alpha levels than patients who only have HCV infection. In coinfected patients, a study also noted that apoptosis correlated with liver damage.2 Further evidence shows that in patients coinfected with HIV and HCV, a high HIV viral load is associated with a high HCV viral load.3 Much of the HIV/HCV coinfection research presented at ICAAC added further details to facts already known, such as that coinfected patients progress more quickly to end-stage liver disease and death. This body of research suggests that HIV/HCV patients often need to be treated first for the hepatitis C infection.
"There are at least 20 studies showing the same thing — that hepatitis C needs to be treated in HIV patients even more importantly than in non-HIV patients because it kills people faster and it makes HIV progress faster," says Douglas T. Dieterich, MD, chief of gastroenterology and hepatology at Cabrini Medical Center in New York City. Dieterich also is associate professor of medicine at New York University School of Medicine.
The risk of lower adherence
One of the problems with treating HIV/HCV patients for both diseases simultaneously is that it increases their medication load, which may result in lower adherence and greater failure rates. A study from Pavia, Italy, evaluated 50 coinfected patients who were treated with HAART and alpha interferon. At 48 weeks, 10 of the patients had achieved virological response to HCV treatment, while 16 patients did not respond and 24 patients had dropped out of treatment because of side effects.4 Also, all of the patients who responded to treatment had a relapse one month after treatment was ended. The study noted that whenever possible, hepatitis C treatment should precede HAART to reduce overlapping toxicity and to improve drug adherence.
However, it is possible to cure coinfected patients of their hepatitis C infection. Dieterich says his center has cured more than 20 HIV-infected patients of their hepatitis C infections. Clinicians should develop a client-based strategy when deciding how and when to initiate HIV and HCV treatment, Dieterich says. "Every situation is different," he says. "If patients do not meet the criteria for HIV treatment yet, then treatment and cure of the HCV is a good idea."
If a patient’s CD4 cell count is less than 350, then Dieterich would recommend the physician treat the patient’s HIV for three to six months and then add HCV treatment. Coinfected patients who have grade 3 liver toxicity are five times the upper limits of normal for the toxicity tests. The best way to treat their liver toxicity is to stop the HIV drugs and get the patient on HCV treatment for about three months, Dieterich says. "Then re-introduce the HIV meds," he adds.
Better treatments available
Hepatitis C treatment has greatly improved in recent years with the addition of ribavirin, a nucleoside analogue, to interferon to create a combination that after six to 12 months of treatment results in sustained normalization of serum levels and a loss of detectable HCV in 30% to 40% of previously untreated patients.5 The most recent development in HCV treatment is the use of long-acting pegylated interferon, given once a week. Studies indicate that this regimen combined with ribavirin may eradicate HCV in more than half of treated patients.
Some HIV antiretrovirals have adverse effects that include liver toxicity, so clinicians need to be vigilant in watching for signs of liver disease when treating coinfected HIV/HCV patients who are on HAART, Klein says. As far as deciding when to start hepatitis C treatment, Klein says he would base that decision on an HIV patient’s health. "If HIV needs to be treated, then that is the most urgent strategy because HIV progresses much more rapidly than HCV," Klein says. "If someone doesn’t need HIV treatment or is on adequate HIV treatment, then the next step is to evaluate them for the need for treatment of HCV."
For HIV patients who have liver disease that is not end-stage and who have active hepatitis C infection, Klein recommends treating the hepatitis C immediately. Whenever HIV patients are coinfected with HCV, it’s important that the HIV physician develop and maintain good communication with the hepatologist treating the patient’s hepatitis infection. "It’s a question of physician comfort and experience, but treating both infections can be complicated," Klein says. "It’s crucial to coordinate, because the last thing you want is for the patient to be given HCV treatment and then not take the medications correctly because there are substantial side effects."
Pay attention to patient behaviors
Physicians treating coinfected HIV/HCV patients also need to pay attention to patient behaviors that put people at risk for early morbidity and mortality, Smith says. "So if your patient has a substantial substance abuse history, either alcohol or injection drug use, it may not be sufficient for overall health care to remind them occasionally that they should receive therapy," she says. "It may be important to play an active role in getting them treated for their substance abuse for a variety of reasons," Smith continues. "These include preventing health conditions that will result from continued abuse of these substances and also to improve overall quality of life and to improve their ability to benefit from HAART therapies."
References
1. Suarez A, Delgado C, Sanchez C, Rodriguez-Agullo JL. HIV infected patients and hepatitis C virus genotypes. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago: Dec. 16-19, 2001. Abstract H-746.
2. Stellrecht KA, Mcelhone A, Providence K. Pathogenesis of hepatitis C virus (HCV) in HIV positive patients. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago: Dec. 16-19, 2001. Abstract H-456.
3. Hsiao C, Gada P, Shelton M, Wu Y. The impact of demographic background, ALT, CD4 and HIV viral load on HCV viral load in HIV/HCV-coinfected patients. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago: Dec. 16-19, 2001. Abstract H-747.
4. Bruno R, Acchi P, Iappina C, et al. Fast relapse and high drop out rate after interferon (ifn) treatment among HIV-HCV coinfected patients. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago: Dec. 16-19, 2001. Abstract H-748.
5. Davis GL. Treatment of hepatitis. Presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago: Dec. 16-19, 2001. Session E-350.