Advances in treatment for human immunodeficiency virus (HIV) have made it possible for people with HIV to survive much longer. As they age, however, many experience impaired thinking, memory loss, mood swings and other evidence of impaired mental function.
To stop these changes, scientists have to learn what is causing them. One possibility researchers are considering is that long-term infections with other pathogens, common in HIV-positive patients, are affecting the brain. But a new study has eliminated one of their prime suspects: the hepatitis C virus, which infects about one in every three HIV-positive patients in the United States.
The research, conducted by a team that includes scientists at Washington University School of Medicine in St. Louis, appeared December 10 in Neurology.
"Hepatitis C infection has serious long-term side effects, such as damage to the liver, but our research indicates that it does not affect the brain," said lead author David Clifford, MD, of Washington University.
The research was conducted as part of the CNS HIV Anti-retroviral Therapy Effects (CHARTER) study, a multicenter collaborative that is examining the long-term neurological effects of HIV infection.
Hepatitis C most commonly infects illicit-drug users who share needles used to inject the drugs. Drug abuse can harm the brain, making it difficult to determine whether hepatitis C or problems caused by drug use contribute to brain impairment in patients with both HIV and hepatitis C.
To answer this question, Clifford and his colleagues studied 1,582 HIV patients, 408 of whom were also infected with hepatitis C. Each patient received a detailed neuropsychological exam devised by Clifford and other CHARTER researchers to detect signs of HIV-associated mental deficits.
The exam takes two to 2 1/2 hours, and includes written examinations taken by the patient and physical exams given by medical professionals. Patients are tested for their ability to express themselves, to make decisions, to learn and retain new information using multiple types of memory, and to move the body and control muscles.
"In all, we looked at seven domains of mental function," said Clifford, who is the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology. "We studied their overall performance and looked at each domain individually and found no evidence that the group with hepatitis C performed worse."
According to Clifford, this was particularly impressive because the participants in the group with hepatitis C were older, had less education and had lower scores on tests of reading, comprehension, spelling and math. With hepatitis C eliminated, Clifford and his colleagues are turning their attention to the immune responses triggered by HIV in the brain and the bowel during the initial stages of infection. He and others believe these early responses, which include bursts of inflammation, lead to chronic inflammation that adversely affects the brain. "If a hepatitis C infection gets to the point where it damages liver function, the resulting inflammation might well contribute to mental impairment," Clifford said. "Beyond that, though, it doesn't seem to be an active collaborator in the harm HIV does to the brain."
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David B. Clifford, Florin Vaida, Yu-Ting Kao, Donald R. Franklin, Scott L. Letendre, Ann C. Collier, Christina M. Marra, Benjamin B. Gelman, Justin C. Mcarthur, Susan Morgello, David M. Simpson, Igor Grant, Robert K. Heaton. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology, Published Online December 10 2014. doi: 10.1212/WNL.000000000000115