We aimed to identify temporal trends in all-cause and cause-specific mortality rates among people who use drugs (PWUD) compared with the general Dutch population and to determine whether mortality trends differed by hepatitis C virus (HCV)/HIV (co) infection status.

Longitudinal cohort study.

Using data from the Amsterdam Cohort Studies among 1254 PWUD (1985-2012), all-cause and cause-specific standardized mortality ratios (SMRs) were calculated; SMRs were stratified by serological group (HCV/HIV-uninfected, HCV-monoinfected, and HCV/HIV-coinfected) and calendar period. Temporal trends were estimated using Poisson regression.

The overall all-cause SMR was 13.9 (95% confidence interval 12.6-15.3). The SMR significantly declined after 1996, especially due to a decline among women (P < 0.001). The highest SMR was observed among HCV/HIV-coinfected individuals during 1990-1996 (SMR 61.9, 95% confidence interval 50.4-76.0), which significantly declined after this period among women (P = 0.001). In contrast, SMR for HCV-monoinfected, and HCV/HIV-uninfected PWUD did not significantly change over time. The SMR for non-natural deaths significantly declined (P = 0.007), whereas the SMR for HIV-related deaths was the highest during all calendar periods.

We found evidence for declining all-cause mortality among PWUD compared with the general population rates. Those with HCV/HIV-coinfection showed the highest SMR. The decline in the SMR seems to be attributable to the decline in mortality among women. Mortality rates due to non-natural deaths came closer to those of the general population over time. However, HIV-related deaths remain an important cause of mortality among PWUD when compared with the general Dutch population. This study reinforces the importance of harm-reduction interventions and HCV/HIV treatment to reduce mortality among PWUD.