Concurrent infection with more than one genotype of hepatitis C virus (HCV) is associated with more rapid HIV disease progression, according to a European study published in the journal AIDS.¹

HIV/HCV coinfection has been linked to more rapid liver disease progression, but its effect on the course of HIV disease progression remains controversial and recent studies have yielded conflicting data. One possible reason for these disparate results is that the effect of hepatitis C on HIV disease progression may vary by HCV genotype.

Researchers with the European Seroconverter Study and the Italian Seroconverter Study analyzed data from 126 HIV/HCV-coinfected injecting drug users from seven European countries -- Austria, France, Italy, The Netherlands, Scotland, Spain, and Switzerland -- with known dates of HIV infection. About two thirds (68 percent) were male, and the average age at HIV seroconversion was 27 years.

Participants' HCV genotypes were determined early in the course of HIV infection. Genotype 1 was most common (48 percent), followed by genotype 3 (34 percent), genotype 4 (13 percent), and genotype 2 (1 percent); 5 percent were infected with more than one HCV genotype (one subject with 1b and 3a; four with 1b and 4; and one with 3a and 4). None of the participants were receiving treatment for hepatitis C.

The researchers analyzed the effect of highly active antiretroviral therapy (HAART), which became available between March 1996 and September 1996 (depending on study site). By July 1997, 60 percent of subjects had started HAART. That percentage increased to 75 percent by January 1999.

Participants with missing CD4 cell measurements or with CD4 counts <200 cells/mm³ at baseline were excluded from the analysis of immunological progression, leaving data from 108 subjects. After a median follow-up period of 7.3 years, subjects with HCV genotype 1 and those with multiple HCV genotypes experienced more rapid immunological progression to a CD4 count <200 cells/mm³ compared with genotype 3 patients (adjusted hazard ratio 2.02, 95 percent CI 1.04-3.92 for genotype 1; hazard ratio 2.74, 95 percent CI 0.95-7.90 for multiple genotypes). When the analysis was limited to pre-HAART data, the differences were even greater (hazard ratio 3.92, 95 percent CI 1.51-10.20 for genotype 1; hazard ratio 4.38, 95 percent CI 1.04-18.40 for multiple genotypes).

After further parsing of data from the entire study period, the researchers determined that the increased risk of immunological decline was linked to infection with HCV genotype 1a, but not 1b. Moreover, subjects with only genotype 4 -- which the researchers identified as being "on the rise among injecting drug users" -- experienced significantly slower immunological progression than those with only genotype 1.

Overall, patients with multiple HCV genotypes also experienced faster clinical progression to AIDS or pre-AIDS death (excluding non-natural causes such as overdose, suicide, or accidents), but this did not reach statistical significance (hazard ratio 3.36, 95 percent CI 0.82-13.79). Looking only at data from the pre-HAART era, however, subjects infected with more than one genotype had a significantly higher risk of clinical progression than those with only genotype 3 (hazard ratio 6.54, 95 percent CI 1.39-30.76). Unlike immunological decline, infection with genotype 1 alone was not associated with more rapid clinical progression, and no significant differences in clinical progression were observed when comparing subjects with only genotype 1, 3, or 4.

The authors concluded that HIV disease progression differs by HCV genotype, "being especially enhanced in those [harboring] HCV infection involving more than one HCV genotype." Given that the difference was much greater before the advent of HAART, they suggested that efficacious combination antiretroviral therapy "may diminish the effect of HCV genotype on HIV disease progression."

In their discussion, the authors noted that it is not yet known how multiple HCV genotypes might cause faster HIV disease progression, although other researchers have suggested that different genotypes many interact differently with HIV, or may have differing effects on CD4 cell proliferation within the liver. Since HCV may be cleared naturally by the immune system or eradicated with treatment, and since prior infection with one HCV strain does not prevent subsequent re-infection, the authors recommended that "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."

Reference

1. Van Asten L, Prins M. Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression. AIDS 2004;18:2313-2318.

Editor's Note: This article is reprinted with permission from www.aidsmap.org, and was first e-published January 26, 2005.