HIV-positive patients coinfected with HCV up to 80% more likely to die even with HIV treatment

Infection with hepatitis C virus increases the risk of death in HIV-positive individuals by between 30% - 80%, even after factors such as the use and success of anti-HIV treatment are controlled for, according to a US study published in the August 15^th edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators, from the US’s largest provider of HIV care, the Department of Veterans’ Affairs, question whether currently available treatment for hepatitis C, which has a lower response rate in HIV-positive individuals, would significantly reduce this level of excess mortality and suggest instead that efforts should be made to treat the high levels of mental illness and drug and alcohol abuse present in their coinfected patients, factors which they believe “contribute directly and indirectly to poor outcome in HIV and HCV coinfection.”

It is estimated that as many as 300,000 HIV-positive individuals (15% - 30% of all HIV cases) are coinfected with hepatitis C virus. Since effective anti-HIV therapy became available, liver disease caused by hepatitis C has emerged as a major cause of illness and death in HIV-positive patients.

Investigators wished to determine the impact of hepatitis C infection on mortality in HIV-positive patients receiving antiretroviral therapy. Their analysis controlled for potential confounding factors including virologic and immunologic response to anti-HIV treatment.

The study included a total of 12,216 individuals who were treated with their first potent anti-HIV treatment regimen at the Department of Veterans’ Affairs between early 1997 and 2003. To be included in the study individuals also had to have been tested for hepatitis C and to have CD4 and viral load tests conducted prior to starting HIV therapy.

A total of 4,668 patients (38%) were coinfected with hepatitis C virus. Coinfected individuals were older than patients who tested negative for hepatitis C and were also more likely to be black or Hispanic, have a history of psychiatric illness (71% versus 60%, p 3 versus 248 cells/mm³).

Hepatitis C-infected and hepatitis C-negative individuals had a similar virologic response to HAART with approximately 80% of both groups of patients achieving an undetectable viral load at least once. Nor was there any difference in the proportion of patients who maintained good control of HIV replication (37% hepatitis C-infected, versus 39% hepatitis C-negative). CD4 cell gain was, however, lower amongst the patients infected with hepatitis C (median peak gain 199 cells/mm³ versus 239 cells/mm³ for hepatitis C-uninfected patients, p

A total of 2087 deaths occurred during follow-up. There were proportionately more deaths amongst hepatitis C virus-infected patients than individuals who were not infected with hepatitis C (22% versus 14%, p

The investigators repeated their analysis, limiting their analysis to patients with controlled HIV replication on at least one occasion and still found that coinfected patients had a significantly higher risk of death (hazard ratio, 1.77, p

“Hepatitis C virus infection increases the risk of death in HIV patients who received HAART, controlling for numerous demographic and clinical factors, including exposure to HAART and response to HAART”, write the investigators. They add, “depending on the factors for which we controlled, we found that the risk of death among HAART-treated HIV patients was between 30% and 80% higher for those who were also infected with HCV.”

The investigators suggest that their study “raises the pressing question of whether HCV treatment can ameliorate the observed increase in the risk of death.” They note that the study was largely completed before pegylated interferon and ribavirin became the standard of treatment for hepatitis C virus. However, they emphasise that the response to hepatitis C therapy is poorer in patients who are coinfected with HIV. They therefore suggest that until better hepatitis C treatment becomes available efforts to treat the high rates of mental illness, and drug and alcohol abuse seen in their cohort may help lower mortality.