All six injection outcome variables and the composite index measure decreased significantly at follow-up compared with baseline among PEI participants, as did all but one measure in the VDI arm (Table 3). Declines in the PEI arm compared with the VDI arm ranged from 26 to 39% across measures, although none reached statistical significance individually. The intervention effect was, however, statistically significant for the composite measure [unweighted average of participants' responses to the six outcome measures; proportional odds ratio (POR) 0.64; 95% CL 0.44, 0.94]. Furthermore, a weighted average from models of the six individual outcome measures demonstrated a 29% greater decline in overall risk among PEI compared with VDI participants (POR 0.71; 95% CL 0.52, 0.97).
Participants within each trial arm reported fewer unprotected sex acts in all categories at follow-up compared with baseline, although not all outcomes were statistically significant (Table 4). A statistically significant difference between trial arms was observed for only one sexual outcome measure. After adjusting for potential confounders, unprotected ‘anal sex with casual/sex trade partners’ decreased more among VDI participants compared with PEI participants. Given a high proportion of zero responses, particularly for the frequency of unprotected anal sex outcomes, we reanalysed the data using zero-inflated negative binomial mixture models. We observed a significantly greater reduction in the frequency component of ‘anal sex with a main partner’ among PEI versus VDI participants (risk ratio 0.54; 95% CL 0.33, 0.87). In addition, there was no longer a significant difference in ‘anal sex with casual/sex trade partners’ by trial arm (data not shown).
The overall incidence of HCV infection was 18.1/100 person-years (95% CL 14.4, 23.0). Using Poisson regression to control for site, race, sex, age, and cohort size, we found no difference in HCV incidence rates between PEI and VDI participants (relative risk 1.15; 95% CL 0.72, 1.82). No participants seroconverted to HIV positive in either trial arm during the 427 person-years of follow-up.
Our intervention, which provided information and skills for reducing sexual and injection risk associated with HIV and HCV infection and encouraged young adult IDU to adopt prosocial roles as peer educators, produced a 29% greater reduction across six injection risk behaviors compared with the attention–control participants. Previous intervention trials among HIV-positive IDU  have demonstrated decreases in unprotected sex and sexually transmitted diseases, but not needle sharing as shown here.
This is the first intervention tested in a randomized controlled trial specifically focused on young HIV and HCV-uninfected IDU that stressed risk reduction for both infections. As HCV is primarily spread through parenteral routes among IDU, interventions that decrease unhygienic injection practices could reduce its spread; and given that HCV-associated liver disease is often silent for decades, interventions that merely delay infection among young IDU could significantly impact public health. Similarly, parenteral HIV transmission would also be decreased. Despite self-reported injection risk reduction in the PEI group, HCV infection incidence did not differ across trial arms, suggesting that exposure to infected blood must be virtually eliminated, rather than simply reduced, to prevent HCV infection. In studies of needlestick injuries sustained by healthcare workers, the proportion of infections after percutaneous injury was 10-fold higher for HCV than HIV . This could also explain why HCV but not HIV transmission readily occurs among IDU who share injection paraphernalia other than syringes.
The effect of the PEI on condom use was less clear. As with injection risk behaviors, the frequency of all sexual risk behaviors declined in both trial arms over time. The only significant difference across arms was a greater decrease in unprotected anal sex with casual/sex trade partners among VDI versus PEI participants. Of note is the fact that this was the least commonly reported sexual risk behavior and less than 8% of men reported being MSM, explaining some of the instability in this estimate. Upon reanalysis using a mixture model, the difference in anal sex with casual/sex trade partners became non-significant. Instead, results from the frequency component indicated that unprotected anal sex with main partners decreased 46% more among PEI than VDI participants. The intervention design assumed that behavior change with steady partners would translate into behavior change among non-steady partnerships; therefore, PEI messages focused mostly on steady partnerships. In retrospect, this assumption may be inaccurate, but could explain why the PEI produced greater, although non-significant, decreases in unprotected sex only with steady partners.
All injection and several sexual risk behaviors decreased significantly at follow-up compared with baseline among PEI participants; however, decreases also occurred among VDI participants, emphasizing the importance of measuring efficacy relative to a concurrent control group. Considering the possibility that participants in both arms learned through successive assessments that underreporting risk behaviors shortened the interview, we compared responses on repeated baseline assessments from participants who had to be reassessed when 3 months had lapsed before they were enrolled. No consistent downward trends in self-reported risk behaviors were found.
Failure to detect significantly greater risk reductions among PEI versus the VDI participants may be caused by features inherent in the trial's design. For example, by giving all participants identical pre and posttest counselling before enrollment, and making condoms, bleach kits, HIV and HCV-related educational pamphlets and medical and drug treatment referrals available in both interventions, all participants received similar information. An overly powerful control condition has the effect of minimizing the relative efficacy of the intervention, which has been observed in previous behavioral intervention trials . Although this trial was not designed to measure community-level effects of the PEI, such an effect was desired. If randomization placed network members into opposing trial arms, PEI participants may have practised what they learned with their VDI arm peers. Consequent reductions in risk behavior among VDI participants would result in underestimating the effect of the PEI on behavior change compared with the control arm.
Our study was limited by the fact that participants had to return for test results to learn of their eligibility, and then had to return for a third visit, sometimes weeks later, for random selection. Consequently, many eligible participants were lost in the process. We thus lost statistical power to detect differences in less prevalent behaviors, such as unprotected sex. Second, intensive risk-reduction training exclusive to the PEI may have caused PEI participants to feel greater pressure than VDI participants to underreport risk behaviors at follow-up in an effort to please their trainers, thus biasing results in favor of the PEI. The use of ACASI to minimize socially desirable responding, and seeing an intervention effect for injection but not sexual behaviors, makes this bias appear unlikely. Third, attrition could have biased results, but 83% returned for at least one follow-up visit and we observed no significant differences between returners and non-returners. Fourth, it is unknown whether our sample is representative of all young adult IDU; however, by employing multiple recruitment strategies in five cities, a broad cross-section of IDU was included. Fifth, intention-to-treat analyses are subject to bias if intervention attendance is low or uneven across arms. Although only 56% of participants overall attended all six intervention sessions, all participants attended at least the first session and attendance at each of the remaining sessions was reasonably high; on average 77% (range 68–100%) of PEI participants and 78% (range 71–100%) of VDI participants attended each session. Furthermore, attendance was similar across trial arms. Finally, sustainability of the intervention effect may not have been measurable in a 6-month follow-up period.
The strengths of this study include the use of a randomized controlled trial design with a dose-equivalent control condition. This design minimized the effect of merely paying attention to participants assigned to the intervention group (Hawthorne effect), which could be significant in marginalized populations such as young IDU. We examined multiple injection and sexual behavioral outcomes, plus a biological outcome, seeking consistency across outcomes to weight empirical evidence of an intervention effect. As behavioral intervention efficacy often degrades over time, we averaged efficacy over a 6-month period to be conservative. Finally, our multisite design provides better generalizability than a single-site trial.
This peer education intervention offers a means for substantially reducing injection risk behaviors among IDU, particularly those who have been injecting for a short time and are at high risk of blood-borne infections. The potential community-wide effects of training peer educators could further impact the spread of HIV and HCV among young IDU. Intensifying the intervention to eliminate, rather than reduce, injection risk may be required to decrease HCV incidence among IDU significantly.
The authors would like to thank Drs Ann O'Leary, Carl Latkin, and Janet Moore for their expert consultation on both the intervention and efficacy trial designs; Drs Kathleen Sikkema and Susan Tross for reviewing and providing invaluable feedback on the pilot intervention; Brigette Finkelstein-Ulin and Linda Moyer (CDC, Division of Viral Hepatitis) for their contribution to the development of the hepatitis educational and counselling materials; and members of Community/Peer Advisory Boards and HIV Program Review Panels at each site for providing constructive feedback on the intervention and trial designs.
The authors would like to recognize the following individuals who made important contributions to the development and implementation of the study: Yvette Bowser, Peter O'Driscoll, Janet Reeves, Marcella Sapun (Baltimore); Angus Atkins-Trimnell, Mary Bonilla, David Cosey, Jaime Delgado, Julio Garcia, Michelle Giles, Erin Kubalanza, Michael Phillips, Edward Snulligan (Chicago); Marrisa Axelrod, Elizabeth Faber, Lawrence Fernandez Jr, Christian Geannette, Roberto Rojas (Los Angeles); Ebele Benjamin, Sebastian Bonner, Micaela Coady, Joanna Cruz, Sandra DelVecchio, Dirk Jackson, Gregory Malave, Joan Monserrate, Danielle Ompad, Clarisse Miller O'Shea, Yingfeng Wu, Manny Yonko (New York); Stanley Brown, Rong Lee, Susan Nelson, Jef St De Lore, Carrie Shriver, Jeanette Frazier, Jean Pass, Paul Swenson (Seattle); Vincent Raimondi, Scott Santibanez, Roberto Valverde (CDC); Wendi Kuhnert, Himal Dhotre, Leigh Farrington, (CDC Division of Viral Hepatitis); Suzette Bartley, Dollene Hemmerlein (CDC Serum Bank Branch).
Other members of the 3rd Collaborative Injection Drug Users Study/Drug Users Intervention Trial (CIDUS III/DUIT) study group include (listed alphabetically): Susan Bailey, Marie Bailey-Kloch, Jennifer V. Campbell, Joyce Fitzgerald, Paige Ingram, Peter Kerndt, Yuko Mizuno, Nadine Snyder, Andrea Swartzendruber, Karla Wagner, David Vlahov, Ian Williams, and Karen Yen-Hobelman.
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