Is there synergy in syndemics? Psychosocial conditions and sexual risk among men who have sex with men in India

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For active syphilis, two-way RERIs were mostly negative or close to zero, except for three pairs involving substance use: depression plus drug use (1.17, 95% CI −0.64 to 2.97), alcohol dependence plus drug use (0.70, 95% CI 0.09-1.30), and alcohol dependence plus childhood sexual abuse (0.33, 95% CI −0.56 to 1.23).

“RERIs from the 2-way syphilis interaction models were mostly negative or close to zero with the exception of three pairs with substance use: depression+drug use (1.17, 95% CI: −0.64 – 2.97), alcohol dependence+drug use (0.70, 95% CI: 0.09–1.30) and alcohol dependence+CSA (0.33, 95% CI: −0.56–1.23)”

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In univariable analysis, there was a dose-response pattern between the syndemic condition count and active syphilis, but no count group reached statistical significance.

“In the univariable analysis of syphilis, there was a dose response pattern of the syndemic count, though no group reached statistical significance”

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In multivariable analysis, there was a dose-response pattern between the syndemic condition count and active syphilis, but no count group reached statistical significance.

“Multivariable analysis was similar to univariable; there was a dose response pattern of the syndemic count with syphilis (adjusted PR for 1 condition vs. none: 1.07, 95% CI: 0.69–1.67; 2 conditions: 1.19, 95% CI: 0.78–1.82; 3 or more conditions: 1.44, 95% CI: 0.78–2.68) but no group reached statistical significance.”

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All other two-way RERIs for recent UAI overlapped the null and were not significantly different from zero.

“All other 2-way RERIs of UAI overlapped the null (zero) and were therefore not significantly different from zero.”

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In the analysis of the behavioral outcome UAI, the authors found significant positive synergistic interaction for only one of eight possible two-way pairs, namely IPV and depression, and no significant positive three-way combinations.

“For the behavioral outcome of UAI, we found evidence of synergistic interaction in only one of the eight pairs of possible 2-way interactions (IPV+depression) and none of the 3-way combinations of syndemic conditions yielded significant positive findings.”

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Seeking medical care for syphilis symptoms was not associated with any of the syndemic conditions, but bias cannot be ruled out if syphilis treatment is associated with syndemic conditions.

“Seeking medical care for syphilis symptoms (i.e. sores and ulcer) was not associated with any of the syndemic conditions but we are unable to rule out bias if treatment for syphilis is associated with syndemic conditions.”

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The count approach produced a linear dose-response relationship for both outcomes, statistically significant for UAI but not for syphilis.

“The count approach for both of our outcomes yielded a linear dose-response relationship, which was statistically significant for UAI but not for syphilis.”

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All three-way RERIs were negative, and those for UAI were all significantly below zero.

“Additionally, all 3-way RERIs were negative, with those for UAI all significantly less than zero.”

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For the biological outcome syphilis, the authors found significant positive synergistic interaction for only one two-way pair, alcohol dependence and illicit drug use, and no significant positive three-way combinations.

“For the biological outcome of syphilis, we similarly found evidence of only one 2-way interaction with substance use (alcohol dependence+illicit drug use) and none of the 3-way combinations yielded significant positive findings.”

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A clustered sandwich variance estimator was used to account for within seed-group correlations in all regression models.

“a clustered sandwich variance estimator was used to account for within seed-group correlations (i.e. clustering by seed chain, n=25) for all regression models (Rogers 1993).”

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A similar pattern was observed for active syphilis, suggesting a dose-response relationship between more syndemic conditions and greater likelihood of syphilis, but the trend was not statistically significant.

“A similar pattern emerged between the syndemic conditions and the biological outcome of syphilis, suggesting a dose-response relationship with more syndemic conditions and greater likelihood of syphilis, but this trend did not reach statistical significance.”

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Multivariable analyses adjusted for city, age, sexual identity, and educational attainment as a priori confounders of the syndemic-syphilis/UAI association.

“multivariable analysis included adjustment for city, age, sexual identity, and educational attainment, a priori confounders of the syndemic-syphilis/UAI association.”

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Depression was measured using the PHQ-9 with a cutoff of 10 or higher, an instrument validated and extensively used in India.

“The presence of depression was measured using a cut-off of 10 or higher on the Patient Health Questionnaire-9 (PHQ-9) (Kroenke, Spitzer et al. 2001), which has been validated and extensively used in India (Kochhar, Rajadhyaksha et al. 2007, Patel, Araya et al. 2008, Ganguly, Samanta et al. 2013).”

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• cites Kochhar, Rajadhyaksha et al. 2007Not checked yet

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• cites Patel, Araya et al. 2008Not checked yet

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Tsai et al. (2017) reported that syndemic studies continue to use the language of synergistic interaction but fail to test for such a relationship in their methods.

“Tsai et al. (2017) reported that while there are signs of greater attention to vulnerable populations both within and beyond the U.S., syndemic studies continue to use the language of synergistic interaction but fail to test for such a relationship in their methods.”

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Five syndemic conditions were chosen based on their previous associations with HIV risk and their frequent use in the syndemic literature.

“Five syndemic conditions were chosen based on their previous associations with HIV risk and their frequent use in the syndemic literature, including alcohol dependence, illicit drug use, depression, intimate partner violence (IPV), and childhood sexual abuse (CSA) (Tsai and Burns 2015).”

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We have previously identified high prevalence of alcohol use, depression and suicidal thoughts, and childhood sexual abuse in our study population.

“We have also previously identified high prevalence of a number of psychosocial conditions associated with syndemics in our study population, including alcohol use (Solomon, Mehta et al. 2015), depression and suicidal thoughts (Tomori, McFall et al. 2016), and childhood sexual abuse (Tomori, McFall et al. 2016).”

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• cites Tomori, McFall et al. 2016Not checked yet

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Alcohol dependence was assessed using the AUDIT instrument with a score of 15 or higher.

“Alcohol use in the past year was assessed using the AUDIT instrument (Saunders, Aasland et al. 1993, Volk, Steinbauer et al. 1997), with a score of 15 or higher categorized as alcohol dependence.”

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• cites Volk, Steinbauer et al. 1997Not checked yet

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Syphilis infection has biological mechanisms that facilitate HIV acquisition and transmission.

“Syphilis infection has further significance because of the biological mechanisms that facilitate HIV acquisition and transmission (Wang, Chen et al. 2014, Paz-Baily, Meyers et al. 2004).”

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• cites Paz-Baily, Meyers et al. 2004Not checked yet

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The most common analytical approach in syndemic studies is an additive count or sum approach that investigates a dose-response relationship.

“The most common analytical approach is an additive (count or sum) approach, wherein the association of the cumulative number of conditions is explored with an HIV behavioral outcome (e.g., unprotected anal intercourse) or prevalent HIV or other sexually transmitted infection, essentially investigating the presence of a dose response.”

• cites Tsai and Burns 2015 sourceNot checked yet

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A substantial body of research has documented that psychosocial conditions cluster among MSM and are associated with greater HIV risk behaviors, often in a dose-response or additive manner.

“Over the past 15 years, a substantial body of research has documented a clustering of psychosocial conditions experienced by MSM, which are associated with greater HIV risk behaviours (e.g., unprotected anal intercourse), often in a dose-response or additive manner (Mimiaga, O’Cleirigh et al. 2015).”

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A study of 4295 men demonstrated that a greater number of syndemic conditions is associated with greater HIV incidence.

“Recently, a study of 4295 men demonstrated that a greater number of syndemic conditions is also associated with greater HIV incidence (Mimiaga, O’Cleirigh et al. 2015).”

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The study used respondent-driven sampling, a chain-referral strategy considered to yield a sample representative of the target population.

“recruited using respondent-driven sampling, a chain-referral strategy for recruiting hard-to-reach participants whereby the resulting sample is considered representative of the target population (Volz and Heckathorn 2008, White, Lansky et al. 2012, Solomon, Lucas et al. 2013).”

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• cites Solomon, Lucas et al. 2013Not checked yet

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Syphilis is currently on the rise among MSM globally, with prevalence estimates of 3-6% of high-titre syphilis among MSM and hijras in southern Indian states compared with 0.5% among the general Indian population.

“Syphilis is currently on the rise among men who have sex with men globally (Abara, Hess et al. 2016, Fenton, Breban et al. 2008), with prevalence estimates of 3–6% of high-titre syphilis among MSM and hijras in southern Indian states (Brahman, Kodavalla et al. 2008) as compared to 0.5% among the general Indian population (Khan, Menezes, et al. 2014).”

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• cites Fenton, Breban et al. 2008Not checked yet

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• cites Brahman, Kodavalla et al. 2008Not checked yet

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The temporal, cumulative development of harmful psychosocial conditions over the life course is a key element of Stall and colleagues' conceptualization of syndemics.

“These issues are currently overlooked in the count approach, yet the temporal, cumulative development of harmful psychosocial conditions over the life course is a key element of Stall and colleagues’ (Stall, Mills et al. 2003, Stall, Coulter et al. 2015) conceptualization of syndemics.”

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• cites Stall, Coulter et al. 2015 sourceNot checked yet

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Ferlatte et al.'s approach, using a slightly different set of syndemic conditions including suicidality but not CSA, yielded evidence of synergistic interaction with three or more conditions, in contrast to the present findings.

“In contrast to our findings, this approach, which used a slightly different set of syndemic conditions (e.g. including suicidality but not CSA), yielded evidence of synergistic interaction with 3 or more conditions.”

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Ferlatte et al.'s findings may indicate that synergistic interactions for syphilis exist in a different population of MSM in a high-income setting.

“Ferlatte et al’s findings may mean that synergistic interactions exist for syphilis in this different population of MSM in a high-income setting, but their methods assume all syndemic conditions have a similar effect on syphilis infection and do not enable us to identify which conditions are in a synergistic relationship with one another.”

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The authors' test case comparing the traditional count approach and a test of synergistic interaction in a large dataset of Indian MSM supports reevaluating current syndemic study approaches and introducing novel methods to test synergy and evaluate co-occurring epidemics over time.

“In conclusion, our “test case” of a comparison of the traditional count approach and a test of synergistic interaction in a large dataset of Indian MSM offers further support for reevaluating current approaches in syndemic studies and for introducing novel methods to test for synergy as well as to better evaluate the development of co-occurring epidemics and their interactions over time.”

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Ferlatte and colleagues (2018) found a strong dose-response relationship between syndemic conditions and active syphilis infection among MSM in Canada using the count approach.

“Similarly, a recent paper by Ferlatte and colleagues (2018) that investigated active syphilis infection among MSM in Canada found a strong dose-response with syndemic conditions and syphilis using the count approach.”

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The authors' findings reinforce the challenge of translating the anthropological concept of syndemics into quantitative population health studies and the need for careful methodological approaches and language in syndemic investigations.

“Our findings reinforce the challenge of translating the anthropological concept of syndemics to quantitative studies of population health and the need for the use of careful methodological approaches (and language) for undertaking syndemic investigations.”

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The authors' findings support the argument by Tsai and colleagues that synergy cannot be assumed from a cumulative relationship between number of syndemic conditions and sexual risk behaviors, and that formal methods are needed to evaluate synergistic interaction.

“Foremost, our findings provide further support for Tsai and colleagues’ (Tsai and Burns 2015, Tsai and Venkataramani 2016, Tsai, Mendenhall et al. 2017) argument that synergy cannot be assumed based on a cumulative relationship of the number of syndemic conditions and sexual risk behaviors and that additional methods are necessary to formally evaluate the presence of synergistic interaction.”

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• cites Tsai and Venkataramani 2016 sourceNot checked yet

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• cites Tsai, Mendenhall et al. 2017 sourceNot checked yet

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Because study populations, selected syndemic conditions, and their measures vary across studies, there is no simple way to compare syndemics across studies.

“Since study populations, the selected syndemic conditions as well as their measures vary from study to study, there is no simple way to compare syndemics across studies.”

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The RERI results indicate that violence and depression interact to increase UAI, whereas substance use interacts to increase syphilis infection.

“The RERIs imply that experiences of violence and depression interact to increase UAI, while substance use interacts to produce increased syphilis infection.”

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Tsai and Burns (2015) observed that many syndemic investigations show a dose-response pattern between syndemic conditions and sexual risk or HIV seroconversion.

“This pattern fits with Tsai and Burns’s (2015) observation that there is a pattern of dose-response relationships with syndemic conditions and sexual risk (or HIV seroconversion) in many syndemic investigations.”

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Tsai and colleagues (2017) note that the first two criteria of syndemics-clustering of epidemics due to harmful social conditions-have been extensively discussed outside the syndemic literature.

“Tsai and colleagues (2017) note that the first two criteria of syndemics about the clustering of epidemics due to “harmful social conditions” has been extensively discussed beyond the syndemic literature.”

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The negative three-way RERIs suggest a lack of synergy beyond pairs, contrasting with the additive count approach that tends to show a dose-response relationship with three or more conditions.

“This suggests a lack of synergy when looking beyond pairs, which constitutes a distinct pattern in contrast to the additive (i.e. count) approach that tends to show a dose-response relationship with 3, 4, or more conditions.”

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Tsai and Burns (2015) and Tsai and Venkataramani (2016) argue that a linear pattern suggests additive effects but does not support substantial synergistic interactions.

“In contrast, however, Tsai and Burns (2015) and Tsai and Venkataramani (2016) point out that such a linear pattern suggests additive effects, but does not support substantial synergistic interactions.”

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The third criterion of synergistic interactions distinguishes syndemic theory from other conceptualizations, but it is problematic because the nature of these interactions is not specific and empirical support is inadequate.

“It is the third criterion of synergistic interactions that distinguishes syndemic theory from other conceptualizations, while also making it problematic due to the lack of specificity about the nature of these interactions and the lack of adequate empirical support for such interactions.”

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Ferlatte et al.'s methods assume that all syndemic conditions have a similar effect on syphilis infection and do not allow identification of which conditions are in a synergistic relationship with one another.

“Ferlatte et al’s findings may mean that synergistic interactions exist for syphilis in this different population of MSM in a high-income setting, but their methods assume all syndemic conditions have a similar effect on syphilis infection and do not enable us to identify which conditions are in a synergistic relationship with one another.”

• cites Ferlatte et al.’s (2018) sourceNot checked yet

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