HIV/HCV coinfection cases require special attention

Experts discuss current treatments, concerns

Until recently, an HIV and hepatitis C (HCV) coinfected patient who was managing well with HIV antiretrovirals might die from liver disease due to HCV infection. Now treatment has advanced, and the health prospects for coinfected patients are brighter than ever.

However, problems and challenges still remain, experts caution.

"Many HIV patients have a history of drug abuse, and in that group, there are a lot of people infected with hepatitis C, hepatitis B, and some with tuberculosis," says Morris Harper, MD, an HIV physician in Waynesberg, PA.

Since the mid-1990s and the widespread use of antiretroviral therapy in the United States, a significant number of patients with HIV/HCV coinfection no longer die from AIDS, but die from HCV, Harper adds.

"Patients who are HIV-positive are good candidates for treatment of hepatitis C and hepatitis B," Harper says.

Saint Michael’s Medical Center in Newark, NJ, has a clinic that specializes in treating HIV/HCV coinfected patients because the care of these patients is time-consuming and requires additional expertise, says Jihad Slim, MD, an assistant professor at Seton Hall University in West Orange, NJ. Slim and colleagues at Saint Michael’s have studied HCV and the immune response.

"Having a clinic for coinfected patients is helpful because you can train nurses and provide specialized treatment," he says.

Hepatitis C is common among HIV patients, but it requires more time spent in clinical care than for HIV disease alone, Slim adds.

"You may have to see the patient every week in the beginning if the person is coinfected and receiving treatment," he explains. "For clinicians who have an interest in doing this, the treatment is doable if they have the time; but unfortunately, not everyone has the time."

Also, small HIV centers may not find it financially feasible to treat a handful of HIV/HCV coinfected patients a year, Slim notes. "You really get the experience and treat patients much more easily once you have treated a dozen coinfected patients."

There are a number of important clinical issues to consider in the treatment of HIV/HCV coinfected patients, including the following:

  • HIV/HCV coinfection causes more complications for each disease.

"In a nutshell, hepatitis C is not a good thing to have when you have HIV," Slim says. "It may not be the worst thing you can have, but it’s not a good comorbid infection with HIV." In addition to increased risk of liver disease, coinfection may cause skin rashes, vasculitis, and other health problems, he explains.

Coinfection also may increase mortality and morbidity, although the research is inconclusive. One recent study showed that AIDS-associated deaths had increased among women who were coinfected with hepatitis C.1

Women coinfected with HIV and hepatitis C were significantly more likely to develop AIDS, explains Andrea Kovacs, MD, director of Maternal, Child and Adolescent Center for Infectious Diseases and Virology at the Los Angeles County, University of Southern California Medical Center. Kovacs also is an associate professor of pediatrics and pathology.

In the population studied, 20% had HCV viral clearance, meaning no HCV replication in the blood, she says.

"They were infected because the antibody was positive, but the virus had not replicated, so they had cleared the virus when they were infected," Kovacs explains. "Then they got HIV after the hepatitis C, and that’s generally what we think happened because we don’t have a date of when they got infected with each virus."

Investigators divided HIV-infected subjects into groups of those who were not HCV viremic; those who were RNA-positive, meaning they were HCV viremic; and those who were HCV-negative. They found that those who were HCV-negative had a rate probability of developing AIDS at three years of 25.9%; those who were HCV-positive but RNA-negative had a rate probability of 20.2%; and those who were HCV viremic had a rate probability of 35%, Kovacs says.

"There was an increased rate of progression among those who were viremic vs. those who were not," she points out. "Our theory was that those who cleared the virus probably have better immunity, but we haven’t studied that group yet."

Although the study started before the era of combination HIV therapy, the study’s predictions included antiretroviral therapy into the adjusted model; and it predicted that hepatitis C independent of HIV therapy was predictive of developing AIDS, Kovacs adds.

Liver problems also appear to be compounded with coinfection, Harper notes.

"Most studies tend to show that untreated HIV tends to worsen the hepatitis C, and that’s why hepatitis C patients who don’t have HIV may take 20 to 35 years to get to that end-stage liver problem, while the patients who are coinfected may get there eight to 10 years sooner," he says.

  • Anemia is bigger problem with coinfection.

Both HIV and HCV can lead to problems with anemia, and the problems could be compounded by some HIV and HCV medications, Harper adds. "AZT in some patients will cause anemia and drop the blood count." Likewise, HCV treatment might lead to anemia, so physicians need to monitor patients for anemia, he advises.

The most recent treatment for hepatitis C is pegylated-interferon alfa-2a (Pegasys) plus ribavirin (Copegus) which is the most effective HCV therapy to date, but that often causes anemia, particularly within the two- to five-week window of treatment, says David Henry, MD, a clinical associate professor of medicine and hematologist/oncologist at the Joan Karnell Cancer Center of Pennsylvania Hospital in Philadelphia.

"HIV patients can be anemic; hepatitis C patients are sometimes anemic; and so coinfected patients are anemic," he says. "Then along came Pegasys and ribavirin; and if patients weren’t anemic before this, medication will certainly make them anemic within two to six weeks."

Henry and co-investigators have studied anemia in coinfected patients being treated for HCV and have found that their anemia could be improved if they were prescribed epoetin alfa (Procrit) to replace the serum erythropoietin their bodies are missing.2

"We found the patients’ ability to make enough EPO when getting Pegasys-ribavirin is about half of normal, and Procrit replaces what they’re missing," Henry explains. Moreover, epoetin alfa is well tolerated and causes no side effects or drug interactions with the HIV and HCV treatments, he says. While HIV clinicians often ignore signs of anemia, paying more attention to other HIV/HCV problems, they’d be remiss in not screening for anemia and treating patients who have hemoglobin values of 10 g/dL or less, Henry notes.

Anemia’s effect on the quality of life

Anemia affects a patient’s quality of life and also may result in a patient missing clinic appointments due to feeling ill and tired. Plus the solution to this problem is easy and well tolerated, he adds. "The most significant time frame for taking Procrit is from two to six weeks after initiating HCV treatment. Since the drug doesn’t work instantly, you might need up to eight weeks of treatment; but the patient won’t need it forever."

  • Depression, neurocognitive problems also can be an issue.

"Depressive symptoms are more common in people coinfected with HIV and HCV, compared with people infected only with HIV," says Howard Libman, MD, director of the HIV program in Healthcare Associates, Beth Israel Deaconess Medical Center in Boston.

Libman and co-investigators studied depressive symptoms, using the Center for Epidemiologic Studies Depression (CES-D) scale among 379 HIV-infected patients who had a history of alcohol problems.3

"What we found were depressive symptoms were significantly more severe in coinfected rather than in just HIV-infected patients," Libman says.

"However, then we tried to adjust for factors that might also affect the likelihood of depressive symptoms like alcohol consumption, gender, age, race, CD4 cell counts, homelessness, injection drug use, and the general status of medical comorbidity that might affect depressive symptoms," he notes. "And when that kind of analysis was done, the difference between HCV-positive and HCV-negative groups diminished significantly."

While HCV coinfection seemed to have some effect on depressive symptoms, it was no longer significantly greater than HIV monoinfection, Libman adds. Research studying the neurocognitive impact on patients who are coinfected have had mixed results, with some smaller studies showing an increase in problems but without identifying a mechanism for how HCV might have direct neurocognitive effects, he says.

Other studies find no difference among coinfected and monoinfected groups. For example, one recent study of 20 HIV/HCV coinfected subjects and 20 HCV monoinfected subjects showed no evidence of greater cognitive impairments between the coinfected and monoinfected groups.4

Depression is fairly common among HIV patients, including coinfected patients, and researchers hypothesize that HIV has a direct impact on brain function and depressive functions, Libman explains.

"I think there will be more abstracts and articles addressing this whole issue of neurocognitive dysfunction and depressive symptoms with HCV/HIV coinfection," he says. "You’ll see more of it in the dual cohort because if HCV does something bad to the brain, you’re more likely to see it first in HIV/HCV coinfected patients."

In addition, depression is common among people with alcohol problems and with patients being treated for HCV with interferon, Libman points out. "Hepatologists are getting more aggressive about treating patients with a history of depression and even those with mild depressive symptoms with a mild antidepressant before starting interferon and ribavirin treatment," he says. "There are enough antidepressants out there that we can usually find an antidepressant drug that can be used in the context of treatment of HIV and HCV."

  • Coinfection and immune function need to be more clearly understood.

Some research has suggested that HCV/HIV coinfection can lead to poor immune response, but this is another area where studies have had mixed results. One recent study did support the theory that HCV could delay immune response to antiretroviral medication in coinfected patients, but liver problems did not appear to play a role.5

"Our main goal was to see if there was a difference in immune change," explains James Fallon, director of infectious disease clinical trials at Saint Michael’s Medical Center. "We were hoping to see that the worse the liver fibrosis, the fewer CD4 cells you would have; but over a year, there was no change."

Investigators based the study on retrospective data that did not differentiate between naïve and memory cells, so their ongoing work is a prospective study that will focus on naïve cells to see if there is an increase of these cells, Fallon adds.

"You want new naïve cells to have a greater increase to show true immune reconstitution," he says. "The thought is if we could eradicate hepatitis C, patients will have a more significant increase in CD4 cell count."

References 

1. Kovacs A, Du W, DeGiacomo M, et al. Impact of HIV viremia on HIV disease progression in women. eJIAS 2004; 1(1):MoPeB3343.

2. Henry DH, Lambiase L, Pierone G, et al. Natural history of anemia associated with interferon/ribavirin (IFN/ RBV) therapy for HIV/HCV coinfected patients. eJIAS 2004; 1(1)MoPeB3301.

3. Libman H, Saitz R, Nunes D, et al. HCV impact on depressive symptoms in HIV-infected adults with alcohol problems. eJIAS 2004; 1(1):MoPeB3280.

4. Thein HH, McAllister J, Dolan G, et al. The impact of antiviral treatment on neurocognitive function and health-related quality of life in HIV-HCV coinfection. eJIAS 2004; 1(1):MoPeB3290.

5. Slim J, Finel DG, Fallon JP, et al. HCV and immune response. eJIAS 2004; 1(1):MoPeB3326.