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Background:  Hepatitis C virus (HCV) infection among HIV-positive injecting drug users (IDU) is almost universal. Studies on the impact of HCV genotype on HIV disease progression are rare: HCV type 1 may be associated with faster HIV disease progression than type 3 in hemophiliacs but this may not be the case for IDU. The effect of infection with HCV type 4 (a genotype on the rise among IDU) and infection with concurrent multiple HCV types on HIV disease progression has not been studied. We studied these questions among a unique group of IDU with a known date of HIV seroconversion and for whom the HCV genotype was determined early in HIV infection.

Methods:  Of 125 HIV-infected IDU with known date of seroconversion and also infected with HCV, the HCV genotype was determined mostly within 3 years of HIV seroconversion by a PCR on the core region (83%) or by Inno-LiPA (17%). Clinical progression of HIV (to AIDS and natural pre-AIDS death combined) and immunological progression of HIV (to a CD4 count of 200 cells/μL) by HCV genotype were studied using Cox proportional hazards analysis. Hazards ratio’s (HR) were adjusted for age, geographic region, setting of recruitment and calendar period. No IDU was treated for HCV infection during the study period (1982 to 2001).

Results:  The median follow-up time was 7.3 years. Compared with HCV genotype 3, clinical and immunological progression were both about 3 times faster among IDU infected with multiple genotypes (adjusted HR:  3.4 and 2.8 and borderline significant, see the table). Immunological progression to 200 CD4 cells/μL was also faster among IDU infected with HCV genotype 1 (adjusted HR: 2.0, p = 0.04). Restricting analyses to the pre-HAART era increased these hazard ratio’s and they became significant. Hepatitis C genotype 4 seemed to be associated with slower progression to all endpoints but not significantly. Further analysis of genotype 1 showed subtype 1a to be associated with immunological progression but not subtype 1b. The (sub)types found among IDU infected with multiple genotypes were 1b, 3a and 4 which separately were not associated with increased HIV progression.

Conclusion:  This study suggests that the impact of HCV on HIV progression differs by HCV genotype and that HIV progression is especially faster in individuals infected with concurrent multiple HCV genotypes. The effectiveness of HAART may diminish the effect of HCV genotype on HIV disease progression.

^*Hazard ratio adjusted for age at HIV seroconversion, calendar period (HAART era vs pre-HAART era), geographic ragion, and setting of recruitment.

^**  Hazard ratio adjusted for age at HIV seroconversion, geographic region, and setting of recruitment.

Keywords: Hepatitis C virus; HIV disease progression; Drug users