Does HIV Impair Immune Response to HCV?

Coinfected patients mount broad & strong response to HIV but not HCV

Tam N Nguyen, Georg M Lauer, Raymond T Chung, Bruce D Walker, MA Gen Hosp and Harvard Medical Sch, Boston, MA

Commentary: This in vitro study (lab study) suggests HIV impairs the human immune response to HCV. Sulkowski's preliminary data, described below, also suggests that. Still, several small preliminary studies report HCV/HIV coinfected individuals have similar response rates to HCV therapy (IFN+RBV). I'm not convinced by these small studies. I think its premature to conclude coinfected individuals will respond as well. The ability to respond to HCV therapy may vary on individual situations. The small studies conducted so far may reflect a highly selected group of individuals, or may not accurately reflection the broad diversity of infected persons. But when looked at the larger population of coinfected individuals response rates may vary significantly, greatly depending again on individual circumstances.

Background and Objective: Co-infection with HIV and HCV offers the opportunity to compare the human immune response towards two different viruses in a single individual. We determined the HLA class I restricted CTL response against HIV and HCV in an Elispot 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 six HCV vaccinia constructs covering the whole HCV protein and four 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 threefold 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. In 17patients we also assessed the proliferative response towards 4 HCV proteins and towards HIV p24.

Results: All 22 HIV/HCV co-infected subjects demonstrated responses to HIV vaccinia constructs in the Elispot assay, with 20/22 targeting two or more. 6/22 patients demonstrated responses to HCV and all but one targeted only one or two of the 6 HCV vaccinia constructs. Cumulative responses to HIV ranged from 140 to more than 3000 SFC/10^6 PBMC with 16/22 having more than 500 SFC/10^ PBMC. The six patients recognizing HCV constructs had cumulative responses of 95, 110, 150, 160, 480 and 520 SFC/10^6 PBMC respectively. In the proliferation assay, 8/17 patients had a significant response to p24 alone, 3 recognized both p24 and one of the 4 HCV proteins. 6 patients showed no significant proliferation at all.

Conclusions: The cellular immune responses to HIV and HCV in co-infected individuals vary distinctively in breadth and strength. Whereas patients are able to mount a relative broad and strong response against HIV, most patients fail to do so against HCV. In those patients with responses to both HIV and HCV, the HCV response never reaches or surpasses the HIV response in breadth or strength. The reason for this failure of the immune system despite its obvious capability to mount a strong and broad response against another virus remains to be determined.
     (Editorial comment: in Mark Sulkowski's study on coinfection at the Johns Hopkins Clinic he reported that they performed HCV-RNA on 215 persons with HCV/HIV coinfection and found 6.8% (14/215) were HCV PCR negative. He said this suggests clearance of the virus. Since this percent is lower than the 15-20% normally found to clear HCV, this suggests HIV patients may be less likely to clear HCV. PCR should be performed because some patients are aviremic).

 LINK to report:

Prevalence and Severity of Liver Disease in HIV Urban Clinic in Baltimore