This study also has a number of limitations, foremost among them

This study also has a number of limitations, foremost among them being the lack of data on continuing IDU among individuals whose presumed transmission route for HIV

acquisition was IDU; and adherence after starting cART, which may find more mediate some of the differences observed. Participating cohort studies in the ART-CC do not collect information on treatment adherence in a standardized manner. Unmeasured confounders may also account for some of these differences in progression rates in IDUs compared with non-IDUs. Further, a greater proportion of IDU deaths were of unknown cause, which may have biased our assessment of the relative importance of different causes of death. Consistent with our results, most previous studies have shown higher rates of mortality in IDUs than in non-IDUs [10,12]; although some have not [6,14,15]. The IDU group was more likely to start cART in the earliest treatment period, an era that has been previously associated with an increased risk for mortality [30]; however, PLX3397 order even with adjustment for this difference, higher rates of death and AIDS were seen among the IDUs. The

most important factors and behaviours contributing to the differences in disease progression we have observed are likely to be adherence to therapy and HCV coinfection. As explained above, we did not have data on adherence, but the poorer immunological and virological responses at 6 and 36 months after starting cART in IDUs compared with non-IDUs are consistent with a role for adherence. Previous studies have shown more rapid disease progression as a result of lower rates of virological response seen in IDUs [31]. Further studies have reported that poor virological outcomes and increased immunological failure on cART among IDUs are often attributable to lack of adherence to therapy [14,17,22]. When not actively using drugs, former IDUs have been shown to have the ability to be adherent to therapy and to achieve comparable benefits to non-IDUs on cART [13,14,17,22,32].

IDUs were also at increased risk for deaths from many diseases not typically thought to be related to HIV infection, such as heart and vascular disease and non-AIDS-related Palmatine malignancies. Given that excesses of these deaths have been demonstrated in untreated individuals [33], it is also possible that these deaths relate to suboptimal treatment of HIV infection in IDUs, as they may be more likely in some settings to remain off therapy for an extended period of time or be less likely to adhere to therapy. In British Columbia, however, IDUs who do adhere have similar outcomes to non-IDUs [15]. IDUs are at increased risk of HCV coinfection [10,12,34], which appeared to explain the excess of liver-related deaths in IDUs compared with non-IDUs.

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