Large European study finds HIV/HCV coinfected patients do not have an increased risk of HIV disease progression

Coinfection with hepatitis C virus does not increase the risk of HIV disease progression or death due to AIDS, according to data from the EuroSIDA cohort to be published in the September 15^th edition of the Journal of Infectious Diseases (now online). The investigators from HIV treatment centre across Europe (as well as some hospitals in Israel and Argentina) also found that coinfected patients had a response to potent anti-HIV therapy comparable to that seen in EuroSIDA cohort members who were only infected with HIV. However, as would be expected, the EuroSIDA data indicated that liver-related death was much higher amongst coinfected patients.

This is the third study to be published recently examining illness and death in coinfected HIV/hepatitis C virus individuals since effective antiretroviral therapy became available. The EuroSIDA conclusion that coinfected patients are no more likely than patients who only have HIV to progress to AIDS or die is in contrast to data from the Chelsea and Westminster Hospital in London, which found that coinfected patients were more likely to progress to AIDS, and the result of a study conducted by the US department of Veterans’ Affairs that found that, even after controlling for demographic factors and response to antiretroviral therapy, coinfected individuals were significantly more likely to die.

“Hepatitis C virus coinfection has become one of the most challenging clinical situations to manage in HIV-infected individuals”, note the EuroSIDA investigators. It is estimated that since effective antiretroviral therapy became available, between 17% - 45% of deaths in HIV-positive individuals in richer countries are due to liver disease.

Studies examining the effect of hepatitis C virus on HIV disease progression have produced conflicting results. There to “clarify this controversy” investigators examined “the clinical outcome and virologic and immunologic responses to highly active antiretroviral therapy in a large group of HIV-infected patients in the EuroSIDA cohort, comparing patients with and without hepatitis C virus coinfection.”

Data on hepatitis C virus infection status on entry to EuroSIDA was available for 5,957 patients who were followed until summer 2004. A total of 1,960 patients (33%) were coinfected with hepatitis C. As expected, injecting drug use was the main mode of HIV infection (71%) for coinfected patients.

On entry to EuroSIDA, viral load and CD4 cell count were broadly similar between coinfected patients and the individuals only infected with HIV, however because of the large number of patients in the sample the differences were statistically significant (coinfected: median viral load 1,600 copies/ml versus HIV patients median viral load 700 copies/ml , p = 0.002; coinfected patients median CD4 cell count 291 cells/mm³versus median CD4 cell count 305 cells/mm³, p = 0.035). In addition, at baseline 27% of coinfected patients versus 21% of patients only infected with HIV had been diagnosed with AIDS, a statistically significant difference (p

On entry to the study coinfected patients were more likely to have abnormal liver function and were likely to also be infected with hepatitis B virus (9% versus 7%, p

During the course of follow-up, a total of 917 AIDS-defining events occurred and there were 819 deaths, of which 109 were related to liver disease, and 462 to non-HIV-related causes.

Significantly more AIDS events (p = 0.024), death from any cause (p

However, after adjustment for baseline factors (p = 0.72) and updated factors, such as changes in CD4 cell count, and starting HIV therapy (p = 0.50), the investigators found that coinfected patients did not have a greater risk of progressing to AIDS. They did however find that coinfected patients had an increased risk of dying, but this was mainly attributable to their increased risk of dying of liver-related causes (p

Data were also analysed for the 2,260 patients who started antiretroviral therapy. A total of 34% of these patients were coinfected with hepatitis C virus. There were no differences between coinfected patients and hepatitis C virus uninfected patients with respect to HIV viral load (approximately 1,600 copies/ml) and CD4 cell count (215 cells/mm³ versus 232 cells/mm³) when HIV therapy was initiated.

A viral load below 500 copies/ml was achieved by 91% of coinfected patients and 89% of patients who were only infected with HIV. There was no significant difference in the length of time it took the two groups of patients to achieve this outcome.

A similar immunologic response to HIV treatment was seen in the hepatitis C virus-infected and uninfected patients with 80% of coinfected patients achieving an increase in their CD4 cell count of at least 50 cells/mm³ and 83% of HCV-uninfected patients achieved this result. Both groups of patients reached this point after a median of nine months of HIV therapy and changes in CD4 cell count after six months of anti-HIV treatment did not differ between hepatitis C virus-infected and uninfected patients.

The investigators conclude, “hepatitis C virus serostatus did not affect the risk of HIV disease progression” and “the overall virologic and immunologic responses to HAART were not affected by hepatitis C virus serostatus.”