Background:  Population-based studies suggest that HCV infection blunts CD4 T-cell responses following initiation of HAART. We explored this effect in antiretroviral therapy naïve individuals enrolled in controlled clinical trials of HAART.

Methods:  We searched a database of patients consecutively enrolled in phase 3 clinical trials of HAART (PI, NNRTI, and triple NRTI) at a single Institution between 1998 and 2003. Data on HCV serology, HIV RNA, and CD4 T-cells count were retrieved from subjects who completed at least 10 laboratory visits and had achieved and sustained plasma HIV RNA below 400 copies/mL at 48 weeks follow-up. Effects of HCV co-infection on absolute CD4 T-cells count over time were evaluated by comparison of median changes from baseline to week 24 and week 48 and by Kaplan Meier curves among HCV antibody positive and HCV antibody negative individuals.

Results:  Of the 229 ART-naïve individuals, who initiated triple combination therapy, 213 achieved plasma HIV RNA below 400 copies/mL at 48 weeks of HAART; 33 (15%) were HCV seropositive and 180 (85%) were HCV seronegative. No significant differences were found in baseline CD4 T cells at initiation of HAART between groups. Mean time to increase 75 CD4 T cells from baseline was 19.9 weeks (CI 95%:  17.4 to 22.4) and 26.1 weeks (19.8 to 32.3) in the HCV seronegative and HCV seropositive individuals respectively (long rank test = 4.23; p = 0.03). Differences remained after adjusting by CD4 and HIV RNA at baseline. There were significant differences in median increase of CD4 T cells count from baseline to week 24 and 48 in HCV seropositives and HCV seronegatives.

Conclusions:  In this selected group of HIV-infected individuals, CD4 T- cell responses at 48 weeks of a successful first HAART regimen, were significantly smaller and delayed among HIV/HCV-co-infected individuals. Intensive monitoring of plasma HIV RNA and CD4 T-cells counts in the context of controlled clinical trials of HAART reproduces prior observations from population-based HIV treatment cohorts. 

Keywords: HCV; CD4; COHORTS