Kidney dysfunction more frequent, increases risk of death of patients with HIV and hepatitis C co-infection

Hepatitis C co-infection is associated with an increased risk of kidney disease and death for HIV-positive individuals, US investigators report in the February 1^st edition of the Journal of Acquired Immune Deficiency Syndromes.

The investigators from the US Department of Veterans’ Affairs found “a significant and graduated relationship between mortality” and poorer kidney function. Moreover, the study revealed “consistently higher adjusted mortality rates among hepatitis C-co-infected veterans at all levels” of kidney function.

Other recently published research has shown the importance of kidney function to the prognosis of patients with HIV.

Since the introduction of effective antiretroviral treatment, the life-expectancy of HIV-positive individuals has increased significantly.

The extent of this improvement was show by one recent study. Its results suggested that with prompt diagnosis and treatment, many HIV-positive patients could expect to live into their 70s.

However, many patients have other chronic co-infections, most notably hepatitis C. Even with antiretroviral treatment, the prognosis for their co-infected individuals is poorer than that for patients who only have HIV.

Chronic kidney disease can be a consequence of both HIV and hepatitis C, and co-infection with these viruses has been linked to a higher prevalence and incidence of kidney dysfunction. Several studies have shown that infection with HIV increases the risk of death due to kidney disease. However, these studies have tended to be small and did not consider the impact of hepatitis C-co-infection.

Therefore, investigators analysed the medical records of 23,155 individuals who received HIV care from the US Department of Veterans’ Affairs between 1998 and 2004.

Information was extracted on a key marker of kidney function, estimated glomerular filtration rate (often abbreviated as eGFR). Patients were defined as having kidney dysfunction if their estimated glomerular filtration rate was below 60 ml/min/1.73m².

The investigators also gathered data on mortality rates and co-infection with hepatitis C.

A total of 40% of patients were co-infected with hepatitis C and 12% of individuals had an estimated glomerular filtration rate below 60 ml/min/1.73m².

Co-infected patients were more likely to have kidney dysfunction than individuals who only had HIV (14% vs. 11%).

There was a significant trend for worsening estimated glomerular filtration rate to be associated with more advanced HIV disease, as indicated by lower CD4 cell count, higher viral load, and progression to AIDS (p < 0.05).

During a median of 7.6 years of follow-up, 37% of patients died. The mortality rate was higher amongst co-infected patients than HIV-monoinfected individuals at all estimated glomerular filtration rates.

Moreover, the risk of mortality increased with worsening kidney function. The mortality rate for co-infected patients with an estimated glomerular filtration rate between 30-59 ml/min/1.73m² was 13.30 per 100 person years compared to a mortality rate of 10.82 per 100 person years for HIV-monoinfected patients with this level of kidney function.

Even higher rates of mortality were seen with poorer kidney function, and once again the risk of death was higher for co-infected individuals. For co-infected patients with an estimated glomerular filtration rate below 15 ml/min/1.73m² (stage 5 kidney disease requiring dialysis or transplant) the mortality rate was 20.39 per 100 person years compared to a mortality rate of 16.58 per 100 person years for patients only infected with HIV.

Statistical analysis showed that compared to individuals with normal kidney function, patients with an estimated glomerular filtration rate below 60 ml/min/1.73m² had a 61% increase in the risk of death. A substantially higher risk was seen for individuals with an estimated glomerular filtration rate below 15ml/min/1.73m² (incidence rate ratio, 2.46; 95% CI, 2.25-2.71).

Furthermore, hepatitis C-coinfection was independently associated with a 24% increase in the risk of death (95% CI, 1.17-1.29).

“Eighty percent of HIV-infected veterans with an estimated glomerular filtration rate below 30 ml/min/1.73m² died during follow-up compared to only one-third of those with normal kidney function at baseline”, comment the investigators, adding “reduced estimated glomerular filtration rate was independently associated with substantially increased mortality.”

They suggest that a quarter of the excess mortality seen in co-infected patients “can be attributed to the higher prevalence of chronic kidney disease.”

‘Veterans coinfected with hepatitis C virus incur…higher rates of chronic kidney disease and mortality than those with only HIV infection”, conclude the investigators. They recommend “efforts should be targeted at optimizing medical care for mono- and coinfected veterans, including antiretroviral therapy, hepatitis C therapy, and control of comorbid conditions.”