Background:  Hepatitis C virus (HCV) co-infection has been suggested to be associated with accelerated development of AIDS and enhanced mortality in HIV⁺ patients. Progression of HIV infection is characterized by gradual CD4⁺ T cell loss. The underlying mechanisms are still only partly understood, but emerging data indicate that apoptosis plays a major role in this cell demise. However, it remains unclear whether HCV co-infection has any additional effect on CD4⁺ T cell apoptosis. Therefore, we studied the level of apoptosis of CD4⁺ T cells in HIV⁺ subjects with HCV co-infection.

Methods:  A total of 81 patients were enrolled in this study including 43 HIV mono-infected (19 with effective HAART, 24 without HAART) and 38 HCV/HIV-co-infected (27 with effective HAART, 11 without HAART) patients. Apoptosis rates of CD4⁺ T cells were analyzed by studying DNA-fragmentation (T.U.N.E.L), expression of 7A6-antigen and cleavage of PARP.

Results:  Confirming previous results we found that treatment-naive HIV⁺ patients displayed significantly higher rates of apoptosis (3.7 %) than healthy subjects (n = 10; 0.9%) or HCV mono-infected patients (n = 9; 0.9%). Of note, apoptosis rates were significantly increased in HCV co-infected, treatment-naive patients (6.1 %) as compared to both HIV mono-infected and healthy subjects. Effective HAART was associated with reduction of CD4⁺ T cell apoptosis in HIV mono- as well as in HIV/HCV co-infection (HIV: 2.1 %; HIV/HCV: 2.1 %), although apoptosis rates still remained higher than in healthy subjects. It is noteworthy that, in these 2 subgroups no significant difference in residual rates of apoptosis could be observed any more.

Conclusions:  Our results demonstrate increased rates of apoptosis in HIV mono-infection, which are even higher in HCV/HIV co-infection. These findings imply enhanced apoptosis to be involved in loss of CD4⁺ T cells during HIV infection and suggest that increased apoptosis could be relevant regarding accelerated progression of HIV in hepatitis C co-infected patients. Furthermore, we present evidence that effective HAART correlates with decreased rates of CD4⁺ T cell apoptosis. In an ongoing prospective study we analyze whether this decline in CD4⁺ T cell apoptosis during effective HAART is associated with immune reconstitution in HIV/HCV co-infection.