Individuals coinfected with HIV and hepatitis C virus are significantly more likely to developed cirrhosis and liver cancer than patients infected with HIV alone, and experience only modest gains in CD4 cell count after starting HAART even with good adherence, according to presentations made to the Second International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris on July 16th.
US investigators looked at the incidence of non-alcoholic liver cirrhosis and hepatocellular carcinoma in 4,761 HIV and hepatitis C coinfected US veterans between 1991 and 2000, and compared these to incidence in over 11,000 veterans infected with HIV alone.
The nine years of the study provided over 60,000 patient years of follow-up. Over this period the total incidence of cirrhosis was 1.47 per 1,000 patient years of follow-up in the hepatitis C-negative patients, but was 15.88 per 1,000 patient years of follow-up in the coinfected patients. When the investigators further analysed their results to establish the rate of cirrhosis in the pre-HAART and HAART eras, they found that following the introduction of effective anti-HIV treatment, coinfected patients became even more likely to develop cirrhosis, with an incidence rate of 20.48 cases per 1,000 patient years of follow-up compared to just 0.92 cases per 1,000 patient years in the hepatitis C-negative patients.
Overall, coinfected patients had a hazard ratio of 10.5 (95% CI, 7.93 – 14.01, p
Coinfected patients were also found to be much more likely to develop liver cancer. When the results of the full nine years of the study were studied, an incidence of hepatocellular carcinoma of 0.20 per 1,000 patient years was seen in the HIV monoinfected patients, but 1.32 per 1,000 patient years in the coinfected patients. Hepatocelllar carcinoma became more common in coinfected patients during the HAART era with incidence increasing to 2.18 per 1,000 patients years. Compared to hepatitis C-negative patients, the coinfected patients had a hazard ratio of liver cancer of 6.08 (95% CI, 2.72 -13.62, p
The investigators stressed that these were the first observation data to show increased incidence and risk of cirrohsis and liver cancer in coinfected patients in the HAART era.
Coinfection also impairs CD4 cell increase after starting HAART
Investigators from Vancouver presented data from the HOMER cohort demonstrating that antiretroviral-naive hepatitis C coinfected patients gained far fewer CD4 cells 18 months after starting HAART than hepatitis C-negative individuals.
Between 1996 and 2000 1,416 HIV-positive patients started HAART, of these 552 (39%) were also infected with hepatitis C. Investigators wished to see the impact of coinfection on CD4 cell gain up to 18 months after HAART. Patients’ adherence was measured using the prescription refill method, with patients collecting 95% of prescriptions classified as adherent.
Baseline characteristics between the coinfected and hepatitis C-negative patients were broadly similar, although coinfected patients had higher baseline CD4 cell counts prior to initiating HAART (290 cells/mm3 versus 240 cells/mm3.
Eighteen months after starting HAART, the average increase in CD4 cell count in hepatitis C-negative patients was 190 cells/mm3, compared to less than 50 cells/mm3 in the coinfected patients. Amongst patients with 95% adherence, the average CD4 cell count in the HIV monoinfected patients was 230 cells/mm3 compared to 120 cells/mm3 in coinfected individuals. This increase was statistically significant for individuals who were hepatitis C-negative (p=0.008), but not for coinfected patients (p=0.122).
When the investigators looked at CD4 cell gain in patients with advanced immune damage and a CD4 cell count below 200 cells/mm3, they again found that hepatitis C-negative patients gained more cells, an average of 78 cells/mm3 after 18 months of HAART (p3 (p
Controlling for all possible confounders, the investigators found that HIV monoinfected patients gained an average of 33 CD4 cells a day, compared to an average loss of eight cells a day in coinfected individuals (p
Giordano TP et al. Does HCV coinfection increase the incidence of non-alcoholic cirrhosis and hepatocellular carcinoma? A cohort study of US veterans. Antiviral Therapy 8 (suppl.1), abstract 213, 235, 2003.
Braiststein P et al. The impact of the hepatitis C virus on CD4 cell response post initiation of HAART among a population-based HIV treatment cohort. Antiretroviral Therapy 8 (suppl.1), abstract 214, 235-6, 2003.