Weak immune system may explain increased risk of death seen in HIV/hepatitis C co-infected patients

HIV-positive patients co-infected with hepatitis C virus whose CD4 cell count is above 300 cells/mm³ have a similar mortality rate to that of individuals who only have hepatitis C infection, Danish researchers report in the February edition of HIV Medicine.

Although the researchers found that overall HIV/hepatitis C co-infected patients had a substantially increased risk of death compared to patients only infected with HIV, they found that the immune suppression caused by HIV explained this increased risk.

Current UK HIV treatment guidelines recommend that HIV treatment should be started when a patient’s CD4 cell count is around 350 cells/mm³, and one of the groups of patients who are particularly encouraged to start treatment at this time is those who are co-infected with HIV and hepatitis C.

Many HIV-positive individuals are co-infected with hepatitis C virus, and liver disease is an increasingly important cause of illness and death in these patients.

A number of studies have examined the impact of hepatitis C co-infection on the prognosis of patients with HIV. These have shown that co-infected patients have an increased risk of death compared to patients only infected with HIV (and to patients infected only with hepatitis C).

However, these studies have often been limited because of their design or because their study sample was small.

Danish investigators therefore designed a nationwide, prospective study comparing outcomes in HIV-positive patients with hepatitis C co-infection to the outcome of patients only infected with hepatitis C.

Using national databases, the investigators identified 483 HIV/hepatitis C co-infected patients and 1932 patients only infected with hepatitis C. The patients with HIV had acquired their HIV infection after they became infected with hepatitis C.

During a total of 12,085 person years of follow-up, 400 people died. This included 129 co-infected patients. These co-infected individuals contributed 2192 person years of follow-up. The mortality rate was 59 per 1000 person years.

The researchers then looked at the mortality rate in the co-infected patients according to their CD4 cell counts.

A total of twelve patients died when their CD4 cell count was above 300 cells/mm³. These patients contributed 529 person years of follow-up and the mortality rate was 23 per 1000 person years.

A much higher mortality rate was seen at lower CD4 cell counts (below 300 cells/mm³), with 117 deaths occurring during 1662 person years of follow-up. The mortality rate amongst these patients was 70 per 1000 person years.

There were 271 deaths during 9894 person years of follow-up amongst the patients only infected with hepatitis C. Their mortality rate, 27 per 1000 person years, was comparable to that seen in co-infected patients with CD4 cell counts above 300 cells/mm³.

The overall five-year probability of survival for HIV/hepatitis C co-infected patients was 0.74, compared to 0.87 for patients only infected with hepatitis C.

The investigators’ first set of statistical analysis showed that co-infected patients had a doubling in their risk of death compared to those only infected with hepatitis C (mortality risk ratio [MMR], 2.1, 95% confidence internal [CI] 1.7-2.6).

However, they adjusted their results for possible confounding factors and CD4 cell count. This showed that HIV/hepatitis C co-infected patients with a CD4 cell count above 300 cells/mm³ had a slightly lower risk of death than patients only infected with hepatitis C (MMR, 0.9, 95% CI: 0.5-1.5).

Co-infected patients with a CD4 cell count below 300 cells/mm³ had a threefold increase in their risk of death compared to patients only infected with hepatitis C (MMR, 3.0, 95% CI: 1.5-5.5).

Starting HIV treatment led to a modest reduction in the risk of death compared to that seen in patients with a CD4 cell count of 300 cells/mm³.

Co-infected patients with a CD4 cell count of 350 cells/mm³ or 500 cells/mm³ did not have a reduced risk of death compared to patients with a CD4 cell count of 300 cells/mm³.

Finally, the investigators repeated their analyses in a group of 117 patients who were infected with hepatitis C after they acquired HIV. The results were comparable to those seen in patients infected with hepatitis C before HIV.

“The excess mortality conferred by co-infection was attributable exclusively to immunosuppression, defined as a CD4 cell count below 300 cells/mm³, comment the investigators.

They conclude, “HIV infection has a substantial impact on mortality in hepatitis C virus-infected individuals, mainly because of the development of HIV-related immunodeficiency.”