Coinfection of HIV and hepatitis C virus (HCV) has been associated with metabolic changes, in particular lipodystrophy and diabetes, which are also linked with antiretroviral therapy. Now, two studies have failed to find a significant link between HIV/HCV coinfection and diabetes or lipodystrophy.
One-third of HIV-positive Americans are thought to be coinfected with HCV: coinfection has been linked previously with fat distribution changes, particularly lipoatrophy, and with diabetes. However, both these metabolic changes are also linked with HIV therapy. Moreover, previous studies have had various limitations. The May 1st edition of the Journal of the Acquired Immune Deficiency Syndromes reports two new US studies that help to clarify previous findings.
Phyllis Tien (University of California, San Francisco) and colleagues measured body composition using magnetic resonance imaging in 1,183 HIV-positive people, from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Multivariate modelling was used to detect associations between various factors, including HIV/HCV coinfection and antiretroviral therapy with body fat at various sites, particularly in the leg.
Investigators from Detroit studied the prevalence of diabetes and associated factors in an antiretroviral - naïve population of 2,565 adults from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Diabetes was diagnosed by self-report, while a subset of participants had fasting blood glucose measurements: findings did not substantially differ when diabetes was confirmed. These findings were compared with those from 6,585 participants in the National Health and Nutrition Examination Survey.
One-fifth of the men and around a quarter of the women in the lipodystrophy study had HIV/HCV coinfection, while 17% of CPCRA participants in the diabetes study also had HCV. CPCRA participants had a significantly lower rate of diabetes than the general population (3.3% versus 4.8%), but the known risk factors of black race, older age, and higher body-mass index were independently associated with diabetes in both cohorts. In univariate analyses, HIV/HCV coinfection was associated with diabetes but multivariate analyses failed to demonstrate an independent association, except possibly among black people. These findings suggest that the linkage between HIV/HCV coinfection and diabetes, in the absence of antiretroviral therapy, “is at best a weak one,” note Brar and colleagues.
In the lipodystrophy study, overall coinfection was not linked with body composition changes when compared with men and women infected with HIV alone. Coinfected men had more leg fat and coinfected women had more visceral fat than people solely infected with HIV, in a multivariate analysis. Stavudine (d4T) in particular (p < 0.001), and also ddI (p = 0.022) and, surprisingly, abacavir (p = 0.012) use were linked with less leg fat in HIV-monoinfected men than in HIV/HCV-coinfected men, while indinavir (p = 0.002) was linked with less leg fat in both groups, and nevirapine was linked with more leg fat in coinfected men (p = 0.016).
Coinfected men had about a 2% loss of leg fat per year of stavudine use compared with 7% in monoinfected men, and there was no significant association between the use of any individual antiretroviral drugs and fat loss. Coinfected women also had slightly smaller decreases in leg fat with increasing duration of stavudine use. “These data suggest that the presence of HCV infection may, in fact, mitigate the leg fat loss that occurs as a result of HIV infection and stavudine use”, the authors note.
The changes in body composition found in the lipodystrophy study are unlikely to have clinical implications, since they would not have been visibly noticeable. However, the findings suggest that “the mechanisms by which HIV, antiretroviral drugs, and HCV may affect fat changes may be more complex than previously hypothesized and warrant further investigation in men and women”. In the diabetes study, “the relatively low prevalence [of diabetes] in the CPCRA cohort contrasts sharply with reports of other investigators”, Brar and colleagues write. Previous studies have found diabetes prevalence varied from 2.8% to 12% of HIV-positive participants, but none of these studies evaluated antiretroviral-naïve patients. The current findings do not preclude the need to screen co-infected patients for diabetes when protease inhibitor therapy is being contemplated. But “the results of the present study emphasize the need to screen patients with classic risk factors . . . Further studies are needed to elucidate the interaction between antiretroviral therapy, especially protease inhibitor therapy, and these other factors”, the authors conclude.