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HCV-Coinfection Is Associated with Diabetes and CD4 Decline
  AIDS Clinical Care December 2003
By Elizabeth R. Jenny-Avital, MD

Researchers recently recognized an association between hepatitis C virus (HCV) infection and diabetes mellitus. Several posters at the IDSA meeting have now demonstrated that HIV/HCV-coinfected patients are even more likely to develop diabetes than patients with either virus alone.
Jain and colleagues retrospectively reviewed 1547 charts from patients attending an HIV outpatient clinic and found that 8.8% had glucose intolerance or diabetes, and 24% had HCV infection. In the univariate analysis, older age, black race, family history of diabetes, and BMI >25 kg/m2 were significantly associated with the presence of diabetes or glucose intolerance. In a multivariate analysis adjusted for age and race, the odds ratio for diabetes or glucose intolerance was 1.6 for patients with HCV-coinfection compared with patients with HIV infection alone. The odds ratio for diabetes or glucose intolerance among coinfected patients was even higher when investigators controlled for elevated BMI and family history of diabetes, further demonstrating the independent association of HCV infection with the development of diabetes.
Butt and colleagues found that among 358 patients with HCV-infection alone, diabetes prevalence was 16%, whereas among 28 HIV/HCV-coinfected patients, diabetes prevalence was 29%. Receipt of PIs -- which have been implicated in the development of glucose intolerance -- was equally prevalent (73%) among those with and without diabetes in the HIV/HCV-coinfected group. However, the roles of HIV per se or PI exposure in this increased diabetes prevalence in coinfected patients compared with patients with HCV alone remain to unclear. In a similar vein, Crane and colleagues determined risk factors for incident diabetes in 1583 patients seen at an urban HIV clinic from 1995 to 2002. In the multivariate analysis, the odds ratios for the development of diabetes were 2.0 for HCV-positive compared with HCV-negative status, 2.7 for black compared with white race, 1.9 for PI-treated compared with PI-naive patients, and 1.05 for each year increase in age.
In other news on the coinfection front, cirrhosis may contribute to CD4-cell count decline in HIV-negative patients, potentially limiting the utility of CD4-cell count as a surrogate for HIV-induced immunosuppression in coinfected patients. McGovern and colleagues examined the relation between CD4-cell count and cirrhosis in 60 HIV-negative individuals, roughly half of whom were HCV-positive. CD4 counts <550, <300, and <200 cells/mm3 were observed in 65%, 28%, and 7% of these patients, respectively. However, the CD4-cell percentage was considered abnormal in only 7% of patients. In the multivariate analysis, only leukopenia was associated with a decreased CD4-cell count. The authors attribute these CD4-cell count declines to hypersplenism.
If HCV infection, in tandem with the severity of liver disease, drives down CD4-cell counts in coinfected individuals, the question becomes whether these CD4-cell counts have the same prognostic value as those in patients with HIV infection alone. To better elucidate the effect of HCV on this surrogate marker for HIV disease, future research should examine the incidence of AIDS endpoints in coinfected patients with low CD4-cell counts. As for the association of HCV-coinfection with diabetes, the clinical implications of these findings have yet to be fleshed out. However, data from future studies examining cardiovascular outcomes and dysglycemia or insulin resistance in HIV-infected individuals should be analyzed in light of patients' HCV status.
Dr. Jenny-Avital is an infectious diseases specialist for the AIDS Consultation Service at Jacobi Medical Center in the Bronx.
Jain MK et al. Hepatitis C infection is associated with diabetes/glucose intolerance in HIV-infected patients. 41st Annual Meeting of the Infectious Diseases Society of America, San Diego, October 2003. Abstract 595.
Butt AA et al. Risk of diabetes mellitus in Hepatitis C and HIV infected patients. 41st Annual Meeting of the Infectious Diseases Society of America, San Diego, October 2003. Abstract 594.
Crane HL et al. Predictors of developing diabetes in HIV-infected patients. 41st Annual Meeting of the Infectious Diseases Society of America, San Diego, October 2003. Abstract 669.
McGovern B et al. Absolute CD4 T-cell subsets are decreased in HIV-seronegative patients with cirrhosis. 41st Annual Meeting of the Infectious Diseases Society of America, San Diego, October 2003. Abstract 603.
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