Background:  The role of hepatitis C virus (HCV) co-infection on CD4⁺ T cell depletion is not well known. Apoptosis has been proposed as a mechanism for CD4 depletion in HIV infection. In co-infected T cells, HCV and HIV might act synergistically, enhancing lymphocyte apoptosis.

Methods:  HIV⁺ subjects without antiretroviral therapy for at least 6 months were randomly selected from our HIV clinic. Plasma HIV RNA and HCV RNA levels, as well as CD4 counts were recorded. HCV⁺ patients were defined as those having detectable plasma HCV RNA. Levels of apoptosis in different subsets of CD4⁺ and CD8⁺ T cells were examined ex vivo in whole blood by Annexin V binding using 4-color flow cytometry. Multivariate linear regression analysis was performed to assess the influence of HCV on levels of apoptosis.

Results:  We analyzed 61 patients:  31 HIV-mono-infected and 30 HIV/HCV-co-infected. Mean age and HIV RNA levels were comparable in mono-infected and co-infected patients, whereas the mean CD4 count tended to be lower in the co-infected group (578 vs 452 cells/mm³; p = 0.07). Memory (CD45RO⁺) and naïve (CD45RA⁺CD62L⁺) subsets of CD4⁺ and CD8⁺ T lymphocytes, as well as their level of activation (CD38⁺) were similar in both groups. Co-infected patients showed significantly higher levels of apoptosis in the naïve subset of CD4⁺ T cells and in the naive and memory subsets of CD8⁺ T cells when compared to HIV-mono-infected patients. After adjusting for age, CD4 counts and HIV RNA levels, HCV co-infection remained significantly associated with higher levels of apoptosis in naive CD4⁺ T cells (b= 0.29; 95%CI 0.2 to 6.4; p = 0.04), naive CD8⁺ T cells (b = 0.32; 95%CI 0.53 to 9.2; p = 0.03), and memory CD8⁺ T cells (b = 0.37; 95%CI 1.3 to 7.6; p = 0.006).

Conclusions:  HCV co-infection is associated with increased apoptosis of T lymphocytes in HIV⁺ patients, which could explain a more rapid CD4 decline and an impaired CD4 recovery following initiation of HAART in co-infected patients.