• Potential conflict of interest: Nothing to report.


One of the most important questions in HIV/hepatitis C virus (HCV)–coinfected patients is the relationship between exposure to antiretroviral therapy (ART) and liver fibrosis. Individual instances of ART-related liver toxicity are well documented, and liver enzyme levels increase to more than 5 times the upper limit of normal in approximately 10% of persons starting new ART.1 However, in some studies, HIV/HCV–coinfected persons taking ART actually had less liver disease.2, 3

As the letter from Macias and colleagues indicates, there are similarities and differences between the results of our studies and others.2–4 In a cohort of 210 HIV/HCV–coinfected persons, we failed to detect less or more liver fibrosis among persons treated with effective ART.5 This finding contrasts with the results of two other studies that suggested ART use might reduce liver fibrosis.2, 3 On the other hand, we did observe that longer and more effective ART was associated with decreased necroinflammatory activity. Because greater necroinflammatory activity was associated with more severe fibrosis in this study, it is possible that a link between ART and fibrosis will manifest itself as individuals have longer exposure to ART. Another difference is that Macias and colleagues observed more advanced fibrosis among those receiving nevirapine, but we failed to detect an association between any specific drug and fibrosis.4

Why the differences? The study populations themselves are different in ways that could affect the findings, because it is impossible to completely account for the multiple confounding factors such as alcohol use, duration of HCV infection, and ART. In these relatively small cross-sectional studies, these types of exposures are difficult to measure accurately. In addition, studies typically only measure these factors at one point in time, which is insufficient to fully account for the variability of these changing exposures.

Whereas the differences between studies remain unresolved, the evidence collectively suggests that ART does not adversely affect liver fibrosis among most HIV/HCV–coinfected patients. Prospective studies with longer follow-up are needed to infer causality from the suggested associations.

Shruti Mehta*, David Thomas*, Mark Sulkowski*, * Johns Hopkins Schools of Public Health and Medicine, Baltimore, MD