Special considerations in the initiation and management of antiretroviral therapy in individuals coinfected with HIV and hepatitis C.

BACKGROUND: Although hepatitis C (HCV) treatment efficacy has improved in recent years, the majority of HIV/HCV-coinfected individuals may not enjoy the full benefits of these treatments and appropriate HIV management is crucial. Evidence is accumulating regarding the impact of HIV/HCV coinfection on the response to, and safety and tolerability of, antiretroviral therapy (ART) in this population.
METHODS: Computerized, English-language literature searches of MEDLINE and PubMed databases (January 1985 to May 2004) for studies of HIV and HCV infection in humans to examine critically (a) the impact of HCV on the HIV virologic and immunologic response to ART; (b) the safety and tolerability of ART in coinfected individuals; and (c) the relationship between immune suppression and immune restoration on hepatic injury.
RESULTS: Three key messages emerged regarding the use of ART in HIV/HCV-coinfected individuals: (a) although HCV appeared to have no impact on HIV virologic response, the data are equivocal regarding immunologic response; (b) morbidities associated with HCV infection, such as insulin resistance, diabetes, mitochondrial dysfunction, and liver inflammation, are also associated toxicities of ART, and (c) both immune suppression and restoration can contribute to the onset and acceleration of HCV-related liver disease.
CONCLUSIONS: The CD4 cell count threshold for initiating ART in HIV/HCV-coinfected patients may be higher because of the impact of immune suppression and restoration on the onset of HCV-associated liver disease and the possibility of a blunted immune response to ART at lower CD4 cell counts. Further, overlapping morbidity between HCV-related mitochondrial and metabolic disease manifestations and ART toxicities warrant careful attention by clinicians.