In this cohort of IDUs, we observed a dramatic decline in HIV infection incidence over 2 decades; no new infections occurred within the first year of follow-up in cohorts recruited in 1998 forward. Reductions in HCV infection incidence and prevalence were also observed over the same period, most notably among persons who had started injection recently and were younger. However, similar prevalences of HCV infection over time among those who were injecting longer and were older suggest that these improvements delay but do not prevent HCV infection at the population level. Collectively, these data support intensifying the harm-reduction strategies that have markedly reduced HIV transmission to reduce further the risk of HCV infection.
Large-scale expansion of NEPs and opiate substitution treatment programs appear to have reduced HIV transmission among IDUs [6
]. Accordingly, in this Baltimore IDU cohort, we have seen marked reductions in HIV infection incidence over 2 decades [10
]. In this analysis, we also detected a decline in HCV infection incidence as well as HCV infection prevalence among those who were younger or had recently started injection. Importantly, we observed that HCV acquisition may be delayed by up to 10 years among IDUs compared with that in the late 1980s when the epidemic was at peak. These results are consistent with a recent meta-analysis by Hagan and colleagues [24
] that suggested that time to HCV infection has lengthened in developed countries as well as a number of reports suggesting declines among younger injectors and new initiates [25
]. Although we hypothesize that these declines are due to expanded harm-reduction efforts and reduction in drug-related risk behavior, our data did not demonstrate that changes in self-reported injection behavior had substantial impact. Of note, we were not able to account for changes in NEP attendance.
Despite reductions in HCV infection prevalence among younger individuals, we did not observe declines in HCV burden in those who were older and had longer injection histories, with the exception of a slight reduction among the most recent cohort compared with the earliest. It is possible that we failed to observe a difference over time among older IDUs with longer history of injection because it will simply take longer for reductions in HCV infection incidence to impact prevalence among older individuals, given that many of the individuals in this older age group were likely infected 20–25 years ago, prior to expanded harm-reduction strategies. This hypothesis is supported by the significantly lower prevalence among older IDUs in the most recent recruitment cohort.
However, it is important to consider other reasons why analogous reductions in HCV infection among older persons with a history of drug injection have not been detected. HCV is an order of magnitude more transmissible than HIV by a single needlestick [12
]. Thus, measures that reduce the likelihood of viral exposure or that reduce the number of viruses in each exposure might be sufficient to affect HIV infection incidence without having a commensurate effect on HCV infection. Interventions such as NEPs and opiate substitution may reach IDUs too late in their injecting careers to have a significant impact on HCV infection incidence. Furthermore, although these measures may reduce the frequency of needle sharing that may be sufficient to impact HIV transmission, they may not completely eliminate risk behavior, making them insufficient to effectively prevent HCV transmission throughout an IDU's injection career.
Data from this cohort and many others indicate the risk of HCV-related liver disease sharply rises in persons aged >40 years [31
]. It is difficult to disentangle the effects of age and duration of HCV infection on disease progression, and despite some public health benefits of delaying HCV infection, it will likely not be sufficient to prevent the long-term complications of disease in a large proportion of IDUs. Even with some reduction in transmission, of the 2005–2008 cohort, >80% of individuals ≥39 years old are infected with HCV and at risk for developing any of the complications associated with chronic liver disease. Furthermore, this level of prevalence points to a large reservoir of HCV infection among this population, which significantly hampers prevention efforts.
Efforts need to be intensified on both the prevention and treatment fronts to reduce the reservoir of HCV-infected IDUs. For many persons, the interval between initiation and injection simply remains too brief for prevention strategies to be successful. Targeting very young IDUs or drug users who have not yet transitioned to injection is critical. However, because transmission continues to occur even among older IDUs, prevention strategies must target IDUs at all stages and ages, and it may be that different strategies are needed for different subpopulations. The other method for reducing the size of the reservoir is HCV infection treatment. Current treatment regimens have limited efficacy among certain subpopulations. In particular, our population in Baltimore is predominantly infected with genotype 1 and African American, with a high prevalence of HIV co-infection, all of which are factors associated with reduced treatment success [34
]. The impact of treatment in reducing HCV burden is likely to have been minimal, because we and others have demonstrated that few IDUs are engaged in care for HCV infection and even fewer successfully clear their HCV infections [40
]. With new, more efficacious therapeutics on the horizon [41
], it is critical that strategies to improve uptake and completion of HCV infection treatment of IDUs be implemented, because treatment is the only option for the large numbers of IDUs already infected with HCV.
We were limited in this analysis by not having HCV testing on the full baseline recruitment cohort; however, the random sample did appear to be similar to the full baseline cohort with respect to key covariates that would be associated with HCV infection prevalence. Our analysis was further limited by the small number of persons who were HCV antibody negative at baseline; this is a common problem in epidemiologic studies among IDUs. All of our behavioral data were collected via self-report, a method that has inherent limitations, some of which may have impaired our ability to assess how much impact behavior change had, particularly in the analysis of HCV infection prevalence. We cannot rule out the possibility of variability in unmeasured individual factors or secular changes across the cohorts that could have impacted prevalence and incidence. Eligibility criteria slightly changed over time, and we observed that a number of factors, including HIV serostatus, differed across recruitment cohorts. Although we adjusted for all measured confounders, we cannot rule out the possibility of residual confounding. Finally, prevalence estimates are impacted by both incidence and mortality, and it is possible that some of the early changes in prevalence observed actually reflect the high levels of mortality due to drug overdose and AIDS in the era prior to the use of highly active antiretroviral therapy (HAART). However, continued declines even after 1996 suggest that some of this difference may be because of reduced incidence as well. Finally, behavioral data were collected by interviewer-administered questionnaire prior to 1998 and via ACASI after 1998, which may have further impacted differences.
These limitations notwithstanding, the data collectively suggest that harm-reduction strategies that have been successful for HIV infection may also be contributing to declines in HCV acquisition. However, additional, more intensive strategies, particularly those that target new initiates into drug injection, are needed to significantly impact community-level drug-related risk. Furthermore, HCV infection prevalence and incidence remain up to 10-fold higher than those of HIV infection in this population, reinforcing not only the continued need for preventive measures but also the need to expand care and treatment to those already infected.