Due to the enhanced risk of rapid progression of liver disease, higher incidence of liver-related complications and higher overall mortality, it is recommended that every HIV/HCV co-infected patient should be evaluated for early HCV treatment . In the present study, we evaluated the treatment decisions and clinical course of HCV/HIV co-infected patients in a real-life treatment setting in a large Northern German university-based cohort in direct comparison to an unselected group of unmatched mono-infected patients treated by the same group of providers.
The first surprising finding is that overall treatment was initiated in only half (88/172) of patients in the entire cohort. Overall SVR was achieved in only 45/88 (51%) of these patients regardless of HIV co-infection status. Our results are in agreement with the results of studies from different parts of the world that show that only a small proportion of the total HCV infected patient population is subjected to treatment and even less are successfully treated . Extrapolating this low number of total successful treatment initiation would have enormous public health consequences [25–27].
This situation might be even worse given the more rapid progression to end stage liver disease in patients co-infected with HCV and HIV . In our current cohort analysis the baseline characteristics of the mono- and co-infected patients with HCV did not differ with regard to stage and severity of liver disease with most patients (group A n = 11; 65% versus group B n = 26; 72%) displaying an early stage of disease (Fibrosis F1- F2). We observed an overall SVR rate of 50% for all genotypes in group A, which is comparable to SVR rates found in randomized clinical trials of peg-INF and ribavirin in HCV/HIV co-infected patients (27% to 40%) [11, 12, 28]. However, the SVR rates in mono-infected patients (52%) are slightly lower than those reported by a real-life cohort study of mono-infected patients treated by gastroenterologists at the same institution in the same time span (60,9%) . The reasons for these differences are not clear, but we have to keep in mind that the ID clinic is attending for international patients, who might have different IL-28 haplotypes . Also, it has to be noted that 9/84 of the mono-infected patients were lost to follow-up.
The majority of patients received PEG interferon alpha 2a , three patients who were treated early in 2000 still received conventional non-pegylated interferon. New direct-acting antiviral agents for hepatitis C genotype 1 infection, such as boceprevir, telaprevir or simeprevir as well as sofosbuvir [17, 18, 30, 31], were not approved yet during the analysed timeperiod.
Despite the satisfactory outcome and an acceptable safety profile, hepatitis C therapy was overall only initiated in half of the patients and even less frequently initiated in HCV/HIV co-infected patients than in HCV mono-infected patients (40% vs. 62%) (p = 0.006) despite the lack of an absolute contraindication according to the chart review in the majority of patients. Reiberger et al.  previously also reported a considerable undertreatment of chronic HCV infection in HCV/HIV co-infected patients in a large multicenter study. While our retrospective mono-center study has many limitations that we are aware of, it resembles a “real-life” setting allowing for an evaluation of attitudes towards HCV treatment initiation of the same infectious disease specialists in mono- versus co-infected HCV patients. In our cohort HCV/HIV co-infected patients received less frequently HCV treatment compared to HCV mono-infected patients (p = 0.006) despite being seen by the same specialized ID staff.
Further studies have to look into the reasons of treatment deferral that could range from a potential contraindication to interferon treatment like depression, anemia or other psychiatric illnesses, or possible objections against treatment initiation because of suspected non adherence and fears from the (co-infected) patient’s perspective, as well as relative lower motivation to initiate treatment from the provider perspective because of the fear of inducing severe side effects or the (assumed) lower SVR rates in co-infected patients . Anecdotally, when confronted with the results of the current study the treating ID specialists were surprised by the high SVR rates seen in co-infected patients -especially for the patients that were not on HAART or with lower CD4+ T cell counts. In a follow up study we plan to assess the provider and patient attitudes towards HCV treatment in mono versus co-infected patients by using standardized questionnaires to better understand the barriers to treatment initiation.
Interestingly, in the group of untreated co-infected patients, all patients were HAART naïve. While deferral of HAART treatment might be an indicator for problems of adherence, it is still interesting that only a minority of patients without concurrent HAART regimes received HCV therapy and these patients showed excellent SVR rates. Although guidelines generally recommend selecting patients for HCV treatment whose CD4+ T cell count is high, no study of pegylated interferon plus ribavirin has shown a significant association between CD4+ T cell count less than 350/μl at treatment initiation and SVR to date [33, 34]. However, the notion that HCV treatment should only be performed in patients who are on concurrent HAART is a very strong held belief and might be a potential barrier for initiating HCV treatment in HIV co-infection.
Despite comparable rates of development of anemia, HCV/HIV co-infected patients received less ribavirin than mono-infected patients during the course of treatment (5764,3 mg/week versus 7567,2 mg/week; p = 0.027), which may have contributed to the slightly lower SVR rates in co-infected patients (50% versus 52%) [12, 15]. It seems that treating physicians are more reluctant to use appropriate weight adapted ribavirin dosages in HCV patients co-infected with HIV. However, this treatment pattern was not warranted since baseline hemoglobin levels were comparable in both patient groups (group A: 14,6 g/dl versus group B: 14,5 g/dl) (Figure 3).
In our analysis, HCV treatment was only initiated in half of the patients of the entire cohort at a University based Infectious Diseases Center. Extrapolating these results for Germany, and taking into account the large proportion of patients who statistically do not clear HCV even after one or several courses of therapy is considered, a great number of HIV/HCV co-infected patients are still in need of efficient antiviral treatment even after one decade of dual combination therapy. Altogether greater efforts to understand and potentially to remove the (provider as well as patient) barriers to evaluation and treatment that still exist for a great proportion of patients have to be undertaken [19, 27].
Limitations to our study include the relatively small number of patients, its retrospective design and an unequal proportion of men and women in the study population. For similar reasons we also abstained from performing more elaborate statistical tests like multivariate analysis.
The lack of data on IL28B genotypes is another limitation to the study. A recent study at our center in mono-infected patients showed that our center attends only a small number of patients with Asian or African origin and approximately 20% of patients show a CC haplotype, 60% a C/T haplotype and 20% the T/T haplotype (unpublished data). We would assume similar proportions of Il28B haplotypes in our co-infected patients, however cannot exclude the possibility of higher rates of patients with a T/T haplotype as discussed above.
We conclude that overall HCV treatment was only initiated in half of the cohort and even in a smaller proportion of HCV/HIV co-infected patients despite satisfactory outcome and similar baseline characteristics. In the light of newer treatment options [17, 18, 30, 31], greater efforts to understand the barriers to treatment that still exist for a great proportion of patients have to be undertaken especially in patients co-infected with both viruses. Additionally, further efforts have to be undertaken to implement the national and international HIV and HCV guidelines to real life practice. Larger prospective studies are needed to confirm our findings in view of newer treatment option including directly acting antivirals (DAA) for HCV infection.