This analysis of HCV treatment outcomes within HIV HCV coinfected subjects within this study highlights and expands on several important areas of research in this field. Firstly, baseline characterisation of these individuals demonstrates that, compared to HCV monoinfected subjects recruited to the study contemporaneously, HIV positive subjects with recently acquired HCV infection represent a significantly different group of individuals. HIV-HCV coinfected subjects were older, more often infected with HCV genotype 1, and considerably more often infected through sexual transmission. Differences were also seen in patterns of drug use in those that did inject. Despite these differences, AHC presents with a similar clinical picture in HIV negative and positive subjects. The shorter duration between estimated time of infection and screening seen in the HIV positive group may reflect heightened awareness of the current acute HCV epidemic specifically within the HIV treatment community.
The recognition of sexual exposure as an important possible route of HCV transmission within the HIV population has been widely reported in recent years, accompanied by a rapid increase in the number of AHC cases diagnosed in HIV positive individuals from across Europe [1
]. Our study is the first to simultaneously enrol HCV monoinfected individuals, using the same sites and protocol, to demonstrate that not only is the occurrence of sexually transmitted AHC also occurring within the HIV population in Australia, but that this group of subjects has distinctly different characteristics from HCV monoinfected individuals acquiring AHC within the same time frame. A case control study from the UK involving 111 HIV positive MSM with AHC identified a number of high-risk sexual behaviours potentially associated with acquisition of infection [17
], but further exploration of the mechanisms of permucosal transmission is still required. Phylogenetic analysis of subjects within the UK case study identified at least seven HCV transmission clusters supporting the role of permucosal transmission within HIV positive networks. Phylogenetic analysis from subjects recruited within ATAHC, both from within injecting and sexual networks, will help examine the extent of clustering and importantly any interaction between HIV positive and HIV negative populations.
Secondly, our study finds an extremely high rate of treatment success in this HIV positive population following a 24 week course of PEG/RBV in acute and early chronic HCV infection. An SVR rate of 80% by ITT is in a similar range to that seen with treatment of AHC in HCV monoinfection [18
] and one of the most successful SVR rates reported in HIV positive subjects to date (). Although based on a relatively small sample size, our study is still one of the largest reported in this setting. The excellent treatment response seen in our HIV positive group rate is especially encouraging given the high proportion of subjects with negative HCV-related prognostic markers at baseline (genotype 1, high baseline HCV RNA). Of particular note in our study is the inclusion of subjects with both acute HCV (as defined by an estimated duration of infection < 6 months) and early chronic HCV (estimated duration of HCV infection between 6 and 18 months). In fact the median estimated duration of infection prior to actual start of treatment was 30 weeks and was greater than 24 weeks in 80% of subjects. Although the numbers involved are small, there was no suggestion that SVR was reduced in those with early chronic infection (SVR 86%) versus those with acute HCV (SVR 77%).There is very little data on treatment outcomes in early chronic HCV infection, either in HCV monoinfected or HIV coinfected subjects, and thus our data is not only novel but also encouraging that 24 weeks PEG/RBV appears to be adequate for the majority of subjects in this group, including those with genotype 1 infection.
Monitoring early virological responses to predict HCV treatment outcome is increasingly common. RVR has been shown in chronic HCV infection to be a useful predictor of treatment outcome, both in HIV negative [22
] and HIV positive subjects [24
]. In acute HCV studies the utility of RVR has been less well-studied. Kamal et al reported an overall RVR rate of 86% [20
] with a positive predictive value of 88% and a negative predictive value of 98%. In our study, although limited by the small sample size, RVR was shown to be an excellent predictor of SVR with 100% positive predictive value. These data suggest that RVR is an important predictor of SVR in AHC as well as CHC.
In summary, this report of the HIV positive subjects treated within our study establishes sexual or ‘permucosal’ transmission of AHC within HIV positive populations to be a global phenomenon. It also suggests that HCV in HIV positive individuals can be successfully treated with 24 weeks combination PEG/RBV not only in acute, but also in early chronic HCV infection. These findings support the importance of regular HCV testing in HIV positive MSM with consideration given to commencing early treatment for recently acquired HCV infection.