The Effect of HAART and HCV Infection on the Development of Hyperglycemia Among HIV-Infected Persons

Several reports have documented an increase in the occurrence of metabolic abnormalities including hyperlipidemia, hyperglycemia, insulin resistance, and overt diabetes mellitus among HIV patients taking HAART, particularly HIV-protease inhibitors. Some studies have suggested removal of the PI or replacing it with a nonnucleoside reverse transcriptase inhibitor such as nevirapine can normalize glucose levels and sometimes reverse diabetes mellitus.

Hepatitis C infection has been independently associated with diabetes mellitus in nearly 30 studies. Due to shared routes of transmission, HCV coinfection occurs in 15-30 percent of HIV patients. The objective of this study was to examine the prevalence and incidence of hyperglycemia according to HCV infection and the type of HAART taken.

The researchers studied 1,230 persons receiving their first HAART regimen from January 1996 through May 2002, and followed them up at six-month intervals. Of the sample, 579 (47 percent) were HCV-negative and 651 (53 percent) were HCV-positive. Persons with HCV coinfection were older, more often African-American, and more likely to use or to have used injection drugs. At baseline, the investigators found no significant differences between HCV-coinfected and uninfected patients in the prevalence of chronic hepatitis B virus infection, baseline CD4 cell counts, HIV RNA levels, or random glucose levels. Subjects with HCV coinfection had significantly higher alanine aminotransferase (ALT) levels and aspartate aminotransferase (AST) levels compared to those without HCV coinfection.

Twenty-two percent (269) were taking a HAART regimen containing an NNRTI, 845 (69 percent) were taking a regimen containing a PI, and 116 participants were taking a regimen containing both a PI and an NNRTI. Persons prescribed PIs were more often male and less frequently African American than participants on other regimens. At baseline, subjects prescribed PIs had lower glucose levels than those on other regimens.

"Among HIV-infected adults receiving medical care in an urban clinic, we observed an increased prevalence of hyperglycemia among persons with HCV coinfection compared with those without HCV infection prior to the initiation of HAART. Moreover, both HCV coinfection and PI use appeared to increase the risk of new-onset hyperglycemia during HAART. Both of these effects were independent of other risk factors of hyperglycemia including age, race, and body weight," the study reported.

"In conclusion," the authors noted, "we observed an increased prevalence and incidence of hyperglycemia among HIV-infected adults with HCV coinfection compared with those without HCV infection. PI use also appeared to increase the risk of hyperglycemia compared with persons receiving NNRTI-containing HAART regimens. Additional prospective studies are needed to better understand the pathogenesis of hyperglycemia among HIV-infected patients receiving HAART, particularly those coinfected with hepatitis C without previously described risk factors such as obesity."

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