In our large multicenter study using MRI-measured regional adipose tissue volume, we found that HIV/HCV coinfection was not associated with less fat when compared with HIV-monoinfected men and women. Our findings are contrary to those of previous studies, which reported an association between HIV/HCV coinfection and peripheral fat loss when compared with HIV-monoinfected individuals. Furthermore, previous studies have not addressed the association of HCV infection with fat changes in HIV-infected women.
We found that HIV/HCV-coinfected women had similar amounts of regional fat when compared with HIV-monoinfected women. HIV/HCV-coinfected men also had similar amounts of regional fat, except in the leg. On average, HIV/HCV-coinfected men had more leg fat than HIV-monoinfected men. The findings of more leg fat in HIV/HCV-coinfected men than in HIV-monoinfected men must be tempered by the fact that the amount of leg fat in HIV/HCV-coinfected men was still less than that in FRAM controls, however.10
When we investigated the association between antiretroviral drugs and leg fat by HCV status, our findings were again contrary to what has been proposed, that the presence of HCV infection and HIV nucleoside analogues may further worsen lipoatrophy. HIV nucleoside analogues, particularly stavudine, have been associated with lipoatrophy, and the proposed mechanism has been thought to be attributable to nucleoside analogue–induced mitochondrial toxicity. HCV has been shown to induce mitochondrial toxicity in the liver.22
Because it is thought that HIV-infected patients usually acquire their HCV infection before HIV infection, it is possible that the mitochondrial toxicity already established as a result of HCV infection does not allow for further toxic effects as a result of HIV infection and NRTIs.
We found that stavudine use was less associated with reduced leg fat in HIV/HCV-coinfected men when compared with HIV-monoinfected men. HIV/HCV-coinfected men demonstrated approximately a 2% loss of leg fat per year of stavudine use (which might imply a loss of approximately 0.08 L [or 70 g] of leg fat in the first year of use for someone starting with 3.29 L [or 2.96 kg] of leg fat; overall mean shown in ), whereas HIV-monoinfected men demonstrated approximately a 7% loss per year of stavudine use (which might imply a loss of approximately 0.2 L [or 180 g] of leg fat for someone starting with 2.8 L [or 2.53 kg] of leg fat). From a clinical perspective, the amount of leg fat lost per year in either group would most likely not be associated with visibly noticeable changes. HIV/HCV-coinfected women also seemed to have slightly smaller decreases in leg fat with increasing duration of stavudine use when compared with HIV-monoinfected women. 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.
There are several possible reasons why our findings differ from those of previous studies. First, our study is the largest to date to investigate the association of concurrent HCV infection (confirmed by HCV RNA testing) on fat changes in a representative cohort of HIV-infected individuals in medical care in the United States. Second, we used MRI measurement of regional adipose tissue volume, whereas other studies used subjective criteria to define lipodystrophy based on self-report and examination. Third, we adjusted for factors known to affect body composition, which had not been done previously in most other studies.
Similar to other published studies, our study is cross-sectional; therefore, we are unable to address fat changes prospectively, and thus to establish a causal relation between HCV infection and fat changes over time. Another limitation of our cross-sectional design is that we could not account for the possibility of survivor bias. The HIV/HCV-coinfected patients included in our study may have had slowly progressive HCV liver disease compared with those not included in our study (who may have died as a result of rapidly progressive HCV liver disease). We did not have histologic data to assess the degree of HCV-related liver disease and how it might be associated with body fat changes. Investigation of the association between regional fat and liver enzyme abnormalities in our cohort is underway.
In summary, our findings contradict previous reports of an association between HIV/HCV coinfection and peripheral fat loss compared with individuals with HIV monoinfection. We found an association between concurrent HCV infection and more leg fat in men compared with those without HCV infection and little apparent association between HIV/HCV coinfection and any regional adipose tissue volume in women. In the absence of direct measures of regional adipose tissue volume in a large cohort of HIV-infected individuals, the findings of other studies must be interpreted with caution. Furthermore, 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.