HCV coinfection linked to faster HIV disease progression in HAART era

Since the introduction of highly active antiretroviral therapy (HAART), HIV positive individuals coinfected with the hepatitis C virus (HCV) are more likely to progress to AIDS than those with HIV alone, according to an Italian study published in the November 19^th, 2004 edition of AIDS.

HIV/HCV coinfection has clearly been linked to more rapid liver disease progression, but research has yielded conflicting data regarding its impact on the course of HIV disease. While most research conducted before the advent of HAART suggested that coexisting HCV had little or no effect on HIV disease, some recent studies indicate that coinfection may accelerate progression to AIDS and/or death.

In an effort to clarify this issue, researchers with the Italian HIV Seroconversion Study collected data from a prospective cohort of individuals newly infected with HIV. Progression to an AIDS diagnosis was analysed on the basis of HCV coinfection status and pre-HAART (June 1991-May 1996) vs post-HAART (June 1996-June 2001) calendar period. Data were collected about every six months for a median follow-up period of 9.7 years.

The study enrolled 1,052 participants (924 pre-HAART and 795 post-HAART) at 18 clinical centres in Italy. All were recent seroconverters who had received a documented negative HIV antibody test followed by a positive test within 24 months; date of seroconversion was estimated to be the mid-point between the last negative and first positive test. About 57% of the subjects had hepatitis C; in most cases, HCV infection occurred prior to study entry and was assumed to precede HIV infection.

The pre- and post-HAART groups were demographically similar. During both time periods, the coinfected subjects were younger than the monoinfected participants at the time of HIV seroconversion (25-26 years vs 29 years), slightly more likely to be male (54% vs 46%), and much more likely to be injection drug users (90% vs 10%). The pre-HAART group (both coinfected and monoinfected) had a higher median CD4 cell count at baseline than the post-HAART group (about 500 vs about 375 cells/mm³), and the former group had a shorter duration of HIV infection (6 years vs 9-10 years).

During the pre-HAART period, slightly fewer coinfected participants developed AIDS compared with monoinfected subjects, but the difference did not reach statistical significance (21% vs 24%, respectively; p = 0.180). During the latter period, the coinfected group was significantly more likely to progress to an AIDS diagnosis (15% vs 9%; p = 0.009). After adjusting for demographic variables including age at the time of HIV seroconversion, the researchers found that HCV coinfection had no significant effect on progression to AIDS in the pre-HAART period (relative hazard = 0.84; 95% CI 0.63-1.11). After the introduction of HAART, the risk of developing AIDS decreased dramatically in both groups. However, having HCV increased the risk of HIV disease progression in the coinfected group relative to that of the monoinfected group (RH = 1.77; 95% CI 1.15-2.73).

The researchers also examined length of time on antiretroviral therapy. During the post-HAART period, coinfected individuals had shorter durations of exposure to combination antiretroviral therapy. The coinfected group took HAART (a regimen of at least three drugs) for 31% of their total time at risk for HIV disease progression, compared with 41% for HIV-monoinfected individuals (p = 0.001). No significant difference in duration was found for dual therapy (29% vs 26% of time at risk, respectively; p = 0.205), but the coinfected group took anti-HIV monotherapy significantly longer (16% versus 8%; p

The authors concluded that while HCV coinfection did not have an appreciable impact on HIV disease progression before the introduction of HAART, coinfected patients progressed more rapidly to AIDS than HIV-monoinfected individuals in the post-HAART era. Since this study controlled for duration of HIV infection, the observed differences “may in part be explained by differences in person-time spent on different antiretroviral regimens,” they wrote.

In their discussion, the researchers suggested that differences in patterns of HAART use - rather than biological factors such as differences in response to antiretroviral drugs - might contribute to the less favourable prognosis for coinfected individuals. For example, the coinfected patients (90% of whom were injection drug users) may have had less ready access to medical care, or may have achieved poorer adherence to therapy. Further, individuals with hepatitis C may have had more difficulty taking antiretroviral medications - or were less likely to have them prescribed - due to concerns about hepatotoxicity. In the pre-HAART era, these differences might have had less impact on HIV disease progression than they do now that effective combination therapy is available.