The study was conducted in a context where study conditions could not be tightly controlled for self-reporting bias, attrition, secular trends, historic factors, and contamination. Our previous randomized controlled trial investigated the possible presence of these conditions and did not find evidence that they influenced results.31 However, the chance that any of these factors may be operating cannot be ruled out. Given the high mobility of this population, 44% of participants missed at least one of the 4 follow-up visits, which is a limitation to our mediation analyses. Incarceration among this population was not uncommon. Overall, 158 participants dropped out of the study. Of those, 37 (23%) were incarcerated, while 103 died and 18 dropped out for other reasons. A total of 58 participants were incarcerated during the study period, and of those, 37 (63.7%) dropped out of the study due to incarceration. However, the rate of incarceration did not differ by study arm and is therefore unlikely to have affected the association between the interventions and mortality. Overall mortality includes mortality that may not be HIV or drug related (in this study, 12%) and therefore might not have been in the path that can be affected by the intervention. Methadone Maintenance Therapy (MMT) was introduced to Thai Nguyen on March 2012. We do not have data on how many participants enrolled in MMT during the last year of the study. MMT may have reduced mortality by preventing drug overdose; however, similar to incarceration, we would not expect there to be a difference in enrollment into MMT by study arm. In addition, several potential mediators, including overdose, social support, and symptoms of depression, were self-reported and social desirability bias may have contributed to our results.
Despite these limitations, our study demonstrates that a multi-level intervention may be effective in increasing survival among HIV-infected PWID. The intervention was well attended by index participants, with 83% attending all sessions at each level. It is important to note that since the completion of the study, there has been a dramatic change in the availability of ART and MMT. ART eligibility guidelines in Vietnam changed in December 2014, to include ART for HIV-infected individuals in mountainous regions and high risk groups (including PWID), regardless of CD4 cell count, and among all other HIV-infected persons, ART for those with CD4 cell count <500 cells/mm3. There are currently 3546 patients on ART in 10 ART clinics in Thai Nguyen province. In addition, the first MMT clinic opened in Thai Nguyen in 2011, during our study. There are currently 6 MMT clinics in Thai Nguyen, with 1729 patients on MMT. Increased access to ART and MMT should in theory, compound the effect of our intervention. To understand the applicability of this intervention to other settings, this intervention may need to be evaluated in settings where social norms may play a less influential role on individual behaviors. This intervention is relatively intense, requiring 2 individual post-test counseling sessions, 2 small support group sessions, and a community-wide video and discussions. To assess the scalability of this program, it may be necessary to consider the cost-effectiveness of this intervention and to explore the minimum intervention dose needed to reduce mortality. Overall, our results suggest the importance of intervening on social and individual factors simultaneously.
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