Infection with Concurrent and Multiple HCV Genotypes Is Associated with Faster HIV Disease Progression

The objective of the present study was to elucidate the importance of hepatitis C Virus (HCV) genotype in HIV disease progression.

This study was conducted among 126 HIV/HCV co-infected drug users with a known interval of HIV seroconversion whose HCV genotype was known early in HIV infection.

Both clinical progression (to AIDS) and immunological progression (to a CD4+ T-cell count of 200 x 106cells/l) by HCV genotype were studied using Cox proportional hazards analysis.

Results

The median duration of follow-up was 7.3 years. The majority of the HCV infections concerned genotype 1 and genotype 3. The distribution was: HCV type 1: 48%, HCV type 3: 34%, HCV type 4: 13%, multiple HCV types: 5%.

Concurrent multiple infections consisted of HCV genotypes 1b+3a, 1b+4 and 3a+4.

HCV genotype 1 and multiple HCV genotype infections were associated with faster immunological progression.

Multiple HCV genotype infection was also associated with faster clinical progression. The hazard ratios increased further and were all significant when analyses were limited to data in the pre-HAART era (HR, 3.92; 95% CI, 1.51-10.20; HR, 4.38; 95% CI, 1.04-18.40 and HR, 6.54; 95% CI, 1.39-30.76, respectively).

Conclusion

The authors conclude, “HIV disease progression differs by HCV genotype and is especially faster in individuals whose HCV infection involves more than one HCV genotype.”

“The effect of HCV genotype on HIV progression was greater in the pre-HAART era, suggesting that the effectiveness of HAART may diminish the effect of HCV genotype on HIV disease progression.”

Discussion

“The effect of infection with genotype 4 or with multiple HCV genotypes on HIV disease progression has not been analyzed previously in any HIV risk group. Among the IDU in this cohort, the number with multiple HCV infections was small but showed HIV disease progression to be significantly enhanced in this group in the pre-HAART era.

“As a greater frequency of unsafe injecting might be expected to be associated with greater risk of multiple genotype infection, these infections may be a surrogate marker for exposure to other blood-borne infectious pathogens, which may contribute to faster progression. However, this is not a likely explanation since no effect of lifestyle factors on HIV disease progression so far has been observed among IDU.

“How multiple genotypes may cause faster HIV disease progression is not known. Sabin et al. suggest two mechanisms that possibly play a role in the association between HCV genotype and HIV disease progression. Firstly, any direct interaction between HCV and HIV may differ by HCV genotype and further, CD4 cell proliferation within hepatic tissue might be HCV genotype-dependent and may affect HIV proliferation.

“A complicating factor when assessing the impact of HCV genotype on HIV disease progression is that HCV infection can be cleared and that infection with one genotype does not protect against infection with another.

“Therefore an individual who remains exposed to HCV (e.g., by risky injecting behavior), may switch from one genotype to another over time or switch from one genotype to multiple genotypes and vice versa, or in due course clear HCV RNA altogether.

“For the present study, however, the researchers assessed the effect of the HCV genotype that was present early in HIV infection. In future, due to the possibility of re-infection and clearance, HCV genotype should ideally be measured prior to HIV infection and longitudinally at different time-points within HIV-infected individuals to gain a better understanding of the effect of HCV genotype on HIV progression.”

12/08/04

Reference
L van Asten and M Prins (for the European Seroconverter Study among injecting drug users). Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression. AIDS 18(17): 2319-2324. November 19, 2004.