HIV and hepatitis C virus (HCV) coinfected patients have a higher risk of hospitalisation and death in the HAART-era than HIV-positive patients who are negative for HCV , according to a Canadian study published in the July 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
There is no consensus on the prognosis of HAART-treated HIV/HCV coinfected patients, as studies have produced conflicting results. Canadian investigators wished to clarify this issue by comparing rates of opportunistic infections, hospitalisation and death between coinfected patients and HIV-infected patients in both the pre and post-HAART eras
A total of 1462 patients were included in the study. The pre-HAART cohort (date of entry, 1989 to 1995) comprised 662 patients, and 539 patients comprised the post HAART cohort (1996 – June 1999). A total of 42 coinfected patients were included in the pre-HAART sample, and 83 in the post-HAART cohort.
Baseline characteristics
In the pre-HAART cohort, the coinfected patients were less likely to have an AIDS diagnosis on entry (12% versus 30%), and have higher median CD4 cell counts (228 cells/mm3 versus 147 cells/mm3). However, the investigators note that these differences could be explained by the shorter duration of HIV infection seen in the coinfected patients, as the majority (64%) entered the cohort in 1994-95.
The HIV/HCV coinfected patients in the post-HAART era were much more likely than the HIV monoinfected patients to have injecting drug use as a risk factor for disease acquisition (83% versus 5%). However, only 19% of the coinfected patients had an AIDS-defining illness at baseline compared to 28% of the HIV patients.
Risk of illness, hospitalisation and death
In the pre-HAART era, the HIV/HCV infected patients had a consistently lower risk of adverse outcome than patients who were only infected with HIV. The rates were 11.0 versus 22.9 per 100 person years of follow-up for opportunistic infections; 6.9 per versus 14.9 per 100 person years of follow-up for death; and 9.7 versus 21.00 per 100 person years of follow-up for hospitalisation.
In the post-HAART era there was no difference in the risk of opportunistic infections between the coinfected patients and the HIV-positive patients (12.8 versus 13.1 per 100 person years).
However, coinfected patients had much greater risk of hospitalisation and death compared to the HIV-positive individuals. The risk of death for the HCV infected patients was 9.5 per versus 5.3 per 100 person years of follow-up, and the risk of hospitalization was 12.8 versus 13.1 per 100 person years.
When the investigators adjusted their data, they found that CD4 cell count and year of entry into the cohort were the only significant predictors of opportunistic infections, hospitalisation, or death.
In the pre-HAART era, AIDS-related causes accounted for a similar proportion of deaths amongst the coinfected and moninfected patients (50% versus 43%). However, in the period after 1996, the main causes of death in patients who also had HCV infection were attributable to non-HIV related infections and complications of injecting drug use (45% versus 15% of HIV monoinfected patients).
HAART utilisation and response
HAART was prescribed to comparable numbers of HCV-positive patients (63%) and HCV-negative patients (60%). Similar proportions achieved a viral load below 500 copies/mL (82% versus 81%), in a comparable period of time. Nor was there any difference between the coinfected and monoinfected patients in the time to virological failure.
However, investigators did find that HCV-positive individuals were significantly less likely to achieve an increase in their CD4 cell count than HCV-negative patients (HR=0.48, 95% CI: 0.23 – 0.97, p=0.04).
Conclusions
Before the introduction of HAART, HCV-positive patients were at no greater risk of disease progression and death than HCV-negative patients, “suggesting that without optimal control of HIV replication, HCV coinfection has little impact on morbidity and mortality as AIDS rapidly ensues.”
After the introduction of HAART, however, HCV-negative HIV-infected patients experienced a 64% reduction in the rate of death and a 14% fall in the rate of hospitalisation. However, “HCV-seropositive subjects did not benefit from this reduction in morbidity and mortality…in the post-HAART era, HCV-seropositive individuals were approximately three-times more likely to die and 2.5-times more likely to be hospitalised compared with HCV-negative individuals.” Even though the rate of HIV-related opportunistic infections was similar for both groups.
Investigators attribute the increased risk of death and hospitalisation seen in the HCV-positive patients to the role of other infections and health risks associated with injecting drug use.
However, they note that HCV-positive patients were just as likely to be prescribed HAART and to achieve a virological response, even though they were 50% less likely to see an increase of 50 cells/mm3 in their CD4 cell count. They offer “cytokine dysregulation associated with ongoing HCV infection” and impaired immune recovery, despite adequate HIV control, as an explanation for this.
They conclude, “our findings suggest that HCV infection, and comorbidity associated with injecting drug use, are preventing the realization of improved health outcomes” in HIV/HCV coinfected patients.
Further information on this website
Hepatitis C - overview
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HIV and hepatitis - booklet in the information for HIV-positive people series (pdf)
Klein MB et al. The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy. JAIDS 33: 365 – 372, 2003.