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Session 84 Poster Session HCV Co-Infection and HIV/HCV Immune Responses Session Time: 4:30-6:30 pm Room 4E-F

640-M. HIV-1/HCV Co-Infection: Comparison of Cellular Immune Responses against 2 Persistent Viruses G. Lauer*1, T. Nguyen1, C. Day1, G. Robbins1, M. Lucas2, P. Klenerman2, R. T. Chung1, and B. Walker1 1 Massachusetts Gen. Hosp. and Harvard Med. Sch., Boston and 2John Radcliffe Hosp., Oxford Univ., UK Background: Co-infection with HIV and HCV offers the opportunity to compare the human immune response towards 2 different viruses in a single individual. We determined the HLA class I restricted CTL response against HIV and HCV in an ElLISPOT assay detecting interferon-gamma secreting cells. The CD4+ T-helper response was assessed using a standard proliferation assay. Methods: Fresh and/or frozen PBMC from 22 subjects with HIV and HCV co-infection were screened for IFN-gamma secretion by ELISPOT assay. PMBC were incubated with 6 HCV vaccinia constructs covering the whole HCV protein and 4 HIV vaccinia constructs expressing gag, nef, RT, and env genes. Responses were seen as positive if the result for a HIV or HCV specific construct was at least 3-fold the result of cells incubated with a vaccinia construct containing the lac-gene alone. Results are expressed in spot-forming cells (SFC) per 10^6 PBMC. HCV responses were additionally tested using tetramer analysis. In 17 subjects we also assessed the proliferative response towards 4 HCV proteins and towards HIV p24. Controls consisted of individuals with HIV-1 or HCV monoinfection. Results: All 22 HIV/HCV co-infected subjects demonstrated responses to HIV vaccinia constructs in the ELISPOT assay, with 12/22 targeting 3 or more. 5/22 subjects demonstrated responses to HCV and all but 1 targeted just 1 of the 6 HCV vaccinia constructs. Cumulative responses to HIV ranged from 140 to > 3000 SFC/10^6 PBMC with 16/22 having more than 500 SFC/10^ PBMC. The 6 subjects recognizing HCV constructs had cumulative responses of maximally 500 SFC/10^6 PBMC. In the proliferation assay, 9/17 subjects had a significant response to p24 alone, but no response was seen to any of the HCV proteins. In a matched group of HCV monoinfected individuals such a response could be detected in 8/17 individuals (p<0.02). Conclusions: We describe robust cellular immune responses against HIV-1 in HIV-1/HCV co-infected individuals in different stages and with different courses of HIV-1 infection. In contrast, HCV-specific T-cell responses in the same individuals are absent or at best of low frequency and narrowly directed despite high levels of ongoing HCV replication. These findings suggest that, while both HIV-1 and HCV are in most cases not effectively controlled by the immune system, HCV and HIV-1 might employ distinct mechanisms to evade immune control.

©2002 9th Conference on Retroviruses and Opportunistic Infections