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Simira cordifolia Hook. Steyerm Rubiaceae is a vascular plant used in Northern Colombia as a source of pigments and wood. However, there is a lack of information regarding its pharmacology and toxicity. This research aimed to study the hydroalcoholic extract of Simira cordifolia as a protector against metal-induced toxicity in Caenorhabditis elegans. Preliminary phytochemical screening of the hydroalcoholic extract of S. Wild-type N2 C. Bioassays demonstrated that HAE-Sc exhibited low toxicity, with significant lethality 4. Growth inhibition reached up to HAE-Sc enhanced the survival rate of the nematode under thermal stress by up to The average lifespan was prolonged by In summary, S. Metabolites from plants offer a diverse range of opportunities to obtain new lead compounds with a wide variety of beneficial biochemical properties. The biodiversity-based research has been focused on finding metabolites with the ability to alleviate the detrimental manifestations of diseases that currently have limited treatments or many adverse effects, such as neurodegenerative disorders, aiming to improve the quality of life for patients Puri et al. Several neuronal-related pathologies display signs and symptoms that resemble those related to prenatal or postnatal exposure to environmental pollutants, in particular heavy metals Nakamura and Lipton, These non-essential toxic elements exert their effects at low concentrations through multiple mechanisms of toxicity, among which oxidative damage stands out, since they generate high levels of reactive oxygen species ROS Kim et al. In Colombia, heavy metal contamination in water, soil, and foods is an issue that affects the health of rural communities, farmers and indigenous people. However, access to therapies against signs and symptoms in rural communities is precarious and the use of natural products derived from plants with antioxidant and antineurotoxic properties is a plausible alternative for managing the signs and symptoms of these diseases Amadi et al. Among the huge arsenal of medicinal plants from Colombian biodiversity, S. Mendoza et al. Simira cordifolia leaves have also been commonly used as a source of pigments, usually isolated employing bark decoction methods, dry or fresh Polesna et al. Despite its number of uses, the chemical composition and phytochemical properties has been poorly documented. In the process of generating knowledge about the bioactivities of natural products, in vivo assays are key to provide the basis for efficacy, adverse effects and modes of action that are relevant to humans, Ha et al. They also offer insights on the relationship between chemical components and the biochemical pathways involved in diseases Pohl and Kong Thoo Lin, There are various in vitro and in vivo biological models available for the evaluation of the bioactivity, beneficial properties, screen for pharmacologically active compounds and toxicity of phytochemicals of foods and plants and to study their mechanisms of action Ayuda-Duran et al. Among these, the nematode Caenorhabditis elegans has significant advantages Xiong et al. It possesses complete systems, muscles, basic physiological processes, and oxidative stress responses comparable to those of higher organisms Zhu et al. It offers various genetic tools, a multitude of transgenic strains for diverse genes of interest, and a fully mapped neural system. Other features such as its lifecycle, morphology, reproduction rate, and simplicity are noteworthy for assessing toxic or beneficial effects in this animal model. Caenorhabditis elegans has demonstrated good predictive capacity when compared to mammalian models Markaki and Tavernarakis, , which has allowed it to be a potential model for assessing the toxicity of various products in their early stages of development, serving as a bridge between in vitro assays and mammalian tests Hunt et al. Numerous studies have reported the adverse effects of nematode exposure to heavy metals. The biotoxicities on C. For instance, Lead Pb exposure has been linked to early neurotoxic sequelae, methylmercury MeHg causes alterations in body length, locomotion, and neurotoxicity, and Cadmium Cd leads to reproductive impairments and oxidative stress, ultimately resulting in Cd-induced neurotoxicity Agarrayua et al. The aim of this research was to study the hydroalcoholic extract of S. All reagents used were of analytical grade. Louis, MO, United States. The bark of S. A voucher specimen No. Plant collection permit was obtained from the Cardique Cartagena, Colombia under Resolution dated 14 June The use of S. The plant material was processed in the laboratories at the University of Cartagena. The bark was quickly washed with Milli-Q water and dried at room temperature. The dried plant material was ground, and dried under vacuum. Next g dried plant material was subjected to extraction maceration for 48 h with a mixture containing ethanol After 24 h, the extract was filtered with Whatman paper, and the plant material was again subjected to the hydroalcoholic extraction for another 24 h. The combined extracts were rotary evaporated up to 40 mL and then freeze dried, Duran-Izquierdo, et al. The hydro-alcoholic extract of the plant HAE-Sc was lyophilized obtaining a final yield of 5. The freeze-dried extract of S. Diluted extract was vortexed and centrifuged at The mobile phase flow rate was 0. Column re-equilibration was performed by returning to A: B at minute 23 and holding until 26 min. Caenorhabditis elegans C. Strain was cultivated under standard laboratory conditions following standard protocols www. To obtain nematode in the same growth period, age synchronization was done by the egg-prep method from the CGC, employing a bleaching solution 0. Age-synchronized worms were cultured on NGM plates containing E. The number of living and dead worms was counted. The nematodes were considered dead when they failed to respond to touch using a platinum loop Nagar et al. For the endpoint tests of growth, locomotion, and reproduction, the concentrations that exhibited low lethality in C. The synchronized N2 worms were treated either the vehicle 0. After exposure, the number of body bends was counted following the recommendations published by Sawin et al. The worms were scored every 24 h until all of them were dead, indicated by their lack of response to radial and physical stimuli. Any worms that disappeared from the plate or died prematurely due to internal hatching or vulval rapture were excluded from the analysis Zhang et al. The number of viable worms was counted every 12 h until all the worms in the control group died. Each experiment used a minimum of 90 worms Jin et al. The experimental design and test procedures were conducted following the previously described methods with minor modifications Duran-Izquierdo et al. Synchronized L4 larvae stage of wild-type N2 worms were exposed to vehicle control or increasing concentrations, of heavy metals, namely, Hg, Pb and Cd. After the h exposure period, the worms were observed under a dissection microscope and classified as either alive, if they were moving, or dead, if unresponsive to gentle probing. The Lethality data were used to estimate LC 50 values. All experiments described here were performed three times with at least three replicates for each treatment. Normality and equality of variances were assessed using the Shapiro-Wilk and Barlett test, respectively. LC 50 for metal mixtures were calculated using Probit analysis. The data of the lifespan assays were processed using a Kaplan-Meier analysis and log-rank test. An ion represented by peak 17, could not be distinguished by its masses and fragmentation profiles; however, they showed fragment ions or losses typical of indole alkaloid class. TABLE 1. Cordifolia extract. Peaks 4, 7 and 8 had molecular loss of C 7 H 12 O 6 , which corresponds to quinic acid, linked by an ester to caffeic acid to form chlorogenic acids, such as chlorogenic acid, and 3-feruloylquinic acid. Interestingly, the monoisotopic mass of peak 13 Strictosamide, was another glycosylated beta-carboline detected in the extract of S. Statistical differences in mean values were observed between the control group 0. The average number of body bends per worm in the control group was Reproduction A , body length B , and body bends C. Longevity curves in N2 C. The mean lifespan of the control group was After 48 h exposure, survival induced by HAE-Sc is not quite evident. The lethality of C. The three heavy metals exhibited high lethality in the nematodes. A—C show the lethality in C. TABLE 2. In the case of Cd, the reduction in lethality was The chemical characterization showed the presence of different chemical groups, all of them with known biological properties. Researchers have corroborated that extracts derived from plants used in traditional medicine contain substances that can improve responses such as life expectancy, reproduction, and the response to oxidative stress in various biological models, including C. The most prominent peak corresponded to harman. This alkaloid has a number of pharmacological properties, including acetylcholinesterase and myeloperoxidase inhibition, antianxiety, antidepressant, antioxidant, hypotensive among others, although concomitantly it possesses considerable adverse effects Khan et al. The low lethality of HAE-Sc, together with its low toxicity in terms of reproduction and growth in the C. Simira cordifolia has few reports in databases mostly deal with its geographical distribution and its use as a dye-producing plant Polesna et al. In addition to the acute toxicity of the extract on the nematode, the study included the assessment of other important toxicological criteria: growth delay, locomotion, and effects on reproduction Xiong et al. This process has been proposed to be mediated by aging-related pathways that control activation of autophagy, mitochondrial biogenesis and the antioxidant machinery, among other mechanisms Aman et al. It is possible that chlorogenic acid, one of the compounds detected in the phytochemical analysis of S. However, more comprehensive research will be necessary to enable the identification of the functional chemical components present in the extract, as well as to understand their interactions. Moreover, quite recently, it has been suggested that harmol, a beta-carboline molecule reported here, improves mitochondrial function and metabolic parameters, extending healthspan Costa-Machado et al. The extract increased the LC 50 in 1. The effects of toxic metals on C. Previous research has demonstrated that the primary mechanism of toxicity of individual heavy metals involves the generation of reactive oxygen species ROS through the depletion of glutathione and the binding to sulfhydryl groups of proteins, presenting itself as one of the fundamental cellular responses, even in the nematode C. The significant effects observed when the lethality induced by the metals was challenged by HAE-Sc is probably due to its antioxidant capacity, also observed for Haematoxylum brasiletto Duran-Izquierdo et al. As oxidative stress participates in the pathogenesis of many diseases in humans Kim et al. The chemical mixture in HAE-Sc may not only interfere with the oxidative stress induced by the metals, it also provides metabolites, such as harman, with protective actions on neurological function via anti-inflammatory effects Piechowska et al. This action of HAE-Sc may be extrapolated to the control of neurodegenerative diseases, where beneficial impacts on oxidative stress, inflammation and neuronal stimulation are main objectives of treatments Murphy and Hartley, ; Peng et al. In summary, we first reported the phytochemical composition of S. The results from the in vivo assays evidenced the potential of compounds from HAE-Sc, to neutralize the damage in C. Further studies are needed to elucidate the signaling pathways involved in the oxidative stress resistance of C. Additionally, it is necessary to conduct research related to the evaluation of other plant parts extracts using fractions with different polarities, in order to identify compounds with higher biological activity. The findings revealed that the extract exerts minimal but significant toxic effects on physiological parameters of the worm in a dose-dependent manner, even though it has a low lethality. Interestingly, it provokes an increase in locomotion in the nematode, suggesting neurological activation. The HAE-Sc prolongs the lifespan, protects against temperature-induced stress, and pre-exposure of the worms to the extract diminishes lethality induced by toxic heavy metals. All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Agarrayua, D. Neurotoxicology of metals and metallic nanoparticles in Caenorhabditis elegans. Caffeoylquinic acids: Chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity. Plant J. Amadi, C. Natural antidotes and management of metal toxicity. Aman, Y. Autophagy in healthy aging and disease. Andrade, V. Neurotoxicity of metal mixtures. Caernohabditis elegans as a model organism to evaluate the antioxidant effects of phytochemicals. Basel, Switz. Bernal, H. Royal Botanic Gardens Kew. Costa-Machado, L. Effects of chlorogenic acid on thermal stress tolerance in C. Phytomedicine 66, Duran-Izquierdo, M. Hydroalcoholic extract of Haematoxylum brasiletto protects Caenorhabditis elegans from cadmium-induced toxicity. BMC Complement. Ha, N. Caenorhabditis elegans as a powerful tool in natural product bioactivity research. Herazo-Vitola, F. Herraiz, T. Hirota, K. N-acetylcysteine restores the cadmium toxicity of Caenorhabditis elegans. Biometals 34 5 , — Huang, S. Chlorogenic acid effectively treats cancers through induction of cancer cell differentiation. Theranostics 9 23 , — Huang, Y. Biological toxicity of heavy metals to Caenorhabditis elegans. PubMed Abstract Google Scholar. Hunt, P. Caenorhabditis elegans for predictive toxicology. Inuki, S. Elucidation of biological mechanisms using synthetic natural products and their derivatives. Yakugaku zasshi J. Jin, S. Kashyap, P. Ajmalicine and reserpine: Indole alkaloids as multi-target directed ligands towards factors implicated in Alzheimer's disease. Khan, H. Kim, D. Association between Pb, Cd, and Hg exposure and liver injury among Korean adults. Public Health 18 13 , Kim, J. Heavy metal toxicity: An update of chelating therapeutic strategies. Trace Elem. Markaki, M. Caenorhabditis elegans as a model system for human diseases. Martins, A. Caenorhabditis elegans as a model to study manganese-induced neurotoxicity. Biomolecules 12 10 , Martins, D. Secondary metabolites from Rubiaceae species. Molecules 20 7 , — Mendoza, H. Rubiaceae de Colombia. Google Scholar. Miao, X. The toxicity assessment of extract of Peganum harmala L. Murphy, M. Mitochondria as a therapeutic target for common pathologies. Nabi, M. Role of environmental toxicants on neurodegenerative disorders. Nagar, Y. Toxicity assessment of parabens in Caenorhabditis elegans. Chemosphere , Nakamura, T. Cell death: Protein misfolding and neurodegenerative diseases. Apoptosis 14 4 , — Peng, L. The synapse as a treatment avenue for Alzheimer's Disease. Phuong, N. Capitelline-A new indole alkaloid from Hedyotis capitellata. Piechowska, P. Nutrients 11 4 , Pohl, F. Polesna, L. Puri, V. Natural product-based pharmacological studies for neurological disorders. Qin, Y. Ligusticum chuanxiong Hort as a medicinal and edible plant foods: Antioxidant, anti-aging and neuroprotective properties in Caenorhabditis elegans. Rangsinth, P. Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans. Rehman, M. Neuroprotective strategies for neurological disorders by natural products: An update. Sawin, E. Neuron 26, — Soares, F. Neurodegeneration induced by metals in Caenorhabditis elegans. Song, S. Protective role of citric acid against oxidative stress induced by heavy metals in Caenorhabditis elegans. Stylianou, M. Distinct transcriptional response of Caenorhabditis elegans to different exposure routes of perfluorooctane sulfonic acid. Sun, X. Tambara, A. Food biochem. Tang, B. High-throughput assessment of toxic effects of metal mixtures of cadmium Cd , lead Pb , and manganese Mn in nematode Caenorhabditis elegans. Chemosphere , — Wang, H. Blueberry extract promotes longevity and stress tolerance via DAF in Caenorhabditis elegans. Food Funct. Ginsenoside extract from ginseng extends lifespan and health span in Caenorhabditis elegans. Wang, L. The biological activity mechanism of chlorogenic acid and its applications in food industry: A review. Xiong, H. An enhanced C. Xu, J. Curcumin supplementation increases longevity and antioxidant capacity in Caenorhabditis elegans. Zhang, Z. Effects of Lycium barbarum polysaccharides on health and aging of C. Zhu, A. Oxidation and antioxidation of natural products in the model organism Caenorhabditis elegans. Antioxidants Basel, Switz. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Simira cordifolia protects against metal induced-toxicity in Caenorhabditis elegans.

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Official websites use. Share sensitive information only on official, secure websites. Competing Interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. The contribution of alcohol use disorders AUDs to known high-risk behaviors associated with HIV transmission in this context has not been well characterized. Between June and October , 5, sexually active MSM were recruited using convenience sampling in five cities to participate in a cross-sectional bio-behavioral survey. Five high-risk sexual criteria previously associated with incident HIV infection in this setting were selected a priori as the dependent outcomes. Unadjusted and adjusted odds ratios AOR were computed to establish the independent correlates of the five dependent outcomes. The majority Strategies that target problematic drinking such as medication-assisted therapy, behavioral counseling and structural interventions could potentially reduce risky behaviors and ultimately reduce HIV transmission among MSM in Peru. While HIV prevalence in Peru remains low at 0. HIV infection in this group has been associated with homosexual self-identification, high-risk sexual behaviors, cocaine use before or during sex, and sexually transmitted infections STI \[3\]. Though many studies assessing the association between alcohol use and HIV risk behaviors have been hampered by the use of non-validated measures of alcohol use and non-specific or non-validated definitions of HIV risk that correlate with HIV incidence, they have nevertheless shown correlations with a variety of risky sexual behaviors \[4\] — \[7\]. Specifically, global, situational, and to a lesser extent event-level studies in North America and Africa have demonstrated associations between alcohol use and risky sexual behaviors \[8\] — \[12\]. International experts have recently called for more comprehensive services for MSM with or at risk for HIV, including screening for and treatment of substance use disorders \[13\]. The extent to which alcohol consumption meets screening criteria as a treatable alcohol use disorder AUD in most available studies has yet to be examined. All procedures were explained to participants, who then read and signed informed consent forms. Sample size was large based on calculations of previous HIV prevalence and incidence data. After informed consent procedures and pre-test HIV counseling, participants underwent HIV and syphilis testing followed by a minute computer-assisted self-administered interview CASI assessing sexual risk behaviors and alcohol and drug use. Afterwards, they underwent post-test counseling, receipt of test results and treatment using Peruvian national guidelines. The 5 dependent variables, high-risk sexual behaviors associated with incident HIV infection, were decided a priori using the Alaska sexual risk criteria for behaviors during the previous 6 months \[14\] : 1 having a STI; 2 self-identification as a sex worker; 3 no condom use during last anal intercourse; 4 anal intercourse with more than 5 partners; and 5 being a sexual partner of an HIV-infected male. Though the AUDIT was initially created as a screening instrument, these AUD cut-offs were subsequently validated for their association with a clinically-defined AUD and the scores have high internal consistency, high sensitivity and specificity and positive predictive value \[15\]. Unlike the timeframe for the dependent variables past 6 months , the 3-month time period for drug use was selected in order to allow for comparisons with previous Peruvian HIV Sentinel Surveillance studies. Bivariate logistic regression analyses were conducted to determine associations between each of the 5 dependent high-risk sexual risk behaviors described above with covariates assessing: 1 demographic factors, 2 AUDs and 3 drug use. Non-parametric testing was used for variables that were not normally distributed. During the 5-month study period, among the 5, final study participants, the majority was below 30 years old, earned low incomes and had at least some secondary schooling. Time constraints were the most common reason for survey non-completion. Table 1 summarizes the characteristics of the 5, participants with complete data. Using standardized screening measures, nearly two thirds Sex workers and participants with multiple partners in the previous six months were more than twice as likely to have an AUD compared to participants who did not engage in sex work or who had fewer sexual partners, respectively. For example, participants reporting more than 5 male partners had 1. Table S1 provides extensive details for model building through inclusion of bivariate and multivariate modeling for each of the five dependent HIV-related risk behaviors. Specifically, bivariate analysis demonstrated significant correlations between all the dependent variables and AUDs, sex work, bisexual orientation, transgender identity, receptive anal intercourse and living outside Lima. Sex workers were more likely to identify as transgendered compared to participants who did not engage in sex work. Sex workers and transgendered participants were less likely to engage in unprotected sex during their last sexual encounter, with unadjusted odds ratios of 0. Table 2 summarizes the final multiple regression findings from Table S1 for each of the 5 high-risk behavior outcomes. After construction of the multivariate logistic regression models, meeting screening criteria for having an AUD remained the only covariate significantly associated with all 5 dependent high-risk behaviors. Recreational drug use independently correlated with three of the five high-risk behaviors and was most strongly associated with being a sex worker. Our study confirms findings from a recent cross-sectional study of Peruvian MSM that documents a high prevalence of alcohol-related problems, but which used the CAGE questionnaire. Though AUDs vary in severity, our assessment that deployed an internationally-validated screening instrument demonstrates that the prevalence of AUDs is extremely high in this population with nearly two thirds Hazardous drinking necessitates, at a minimum, counseling with the recommendation to reduce drinking linked to provision of educational materials that not only provide information about alcohol's potential for harm to the patient and to others, but motivation to reduce heavy drinking due to the increased likelihood of progressing toward more severe AUDs. For HIV prevention purposes, reducing the progression to alcohol dependence, or more severe drinking, would likely be associated with decreased HIV risk behaviors since heavy drinking days are associated with increased risk-taking \[16\]. Those meeting screening criteria for harmful drinking should likewise undergo counseling content similar to that for hazardous drinking, but would also require additionally monitoring and ongoing counseling. The interventions for hazardous and harmful drinking can be brief and may take various forms, ranging from providing 5 minutes of counseling about cutting down on drinking, to several brief sessions, depending on the severity of alcohol consumption and its effect on health, legal or social problems. At a minimum, the AUDIT creators suggest that the content of counseling sessions: i present screening results; ii identify risks and discuss consequences; iii provide medical advice; iv solicit patient commitment; v identify specific goals, specifically reduced drinking or abstinence; and vi give advice and encouragement \[17\]. Alcohol intoxication and drug use increases sexual risk behaviors via various mechanisms including drinking environments, expectancies about its sexual enhancement, its neurocognitive effects and associated poor decision-making \[12\]. Second, disinhibiting substances may help overcome the taboo associated with stigmatizing behaviors. Finally, men whose first MSM sexual encounter that involved alcohol or drugs are more likely to continue using them in subsequent sexual encounters \[18\]. Equally disturbing is the high proportion of participants Central to our study was that the presence of AUDs was significantly associated with all five high risk behaviors assessed in our survey, based on the Alaska sexual risk criteria, that have been associated with HIV transmission \[14\]. Specifically, AUDs were associated with: 1 having more than five sexual partners; 2 unprotected sex during last sexual encounter; 3 having a STI; 4 commercial sex work; and 5 sex with an HIV-infected partner — in the previous six months. Moreover, there was an increasing linear association between AUD severity level and all of these outcomes. A number of studies have shown that behavioral interventions to reduce alcohol consumption alone have a small or negligible effect; the most effective method to treat AUDs is treatment with medication-assisted therapies \[24\]. Though it is seductive to speculate that the disinhibiting effects of alcohol directly cause the high risk-taking behaviors observed in this sample, but the cross-sectional nature of this study only allows us to examine the strength of such associations without proving causality. Event-level granularity that establishes concurrency between alcohol use and risky behaviors, however, is needed to determine if it is the disinhibiting effects of alcohol or, alternatively, unique personality traits, that directly contribute to increased sexual risk \[25\] , \[26\]. Specifically, personality traits associated with sexual adventurism have been independently associated with lack of condom use and alcohol abuse, but not all individuals who are sexually adventurous use alcohol or drugs \[27\] , \[28\]. Disentangling causality would therefore better inform interventions for MSM because the type of intervention needed would differ significantly between those whose sexual risk is preceded by alcohol use versus others whose personality traits lead to sexual adventurism \[25\]. This is particularly relevant since AHI is associated with high levels of onward HIV transmission since viral replication is inordinately high \[31\] and the presence of AUDs is associated with disinhibition and sexual risk. Interestingly, having an AUD was one of the strongest correlates for engaging in sex work. Among the transgendered community in Peru, many transgendered women are involved in sex work \[32\]. Many sex workers admit to consuming increased levels of alcohol during their sexual encounters with clients, upon the insistence of their clients. Additionally sex workers often recruit clients in nightlife venues where drinking is prevalent. The more time a sex worker spends in such venues, the more likely they are to engage clients. Increased time in these settings, however, potentially results in increased time consuming alcohol \[33\]. These data are consistent with prior studies documenting a relationship between drug use and risky sex among MSM \[26\] , \[34\]. It should be noted, however, that the prevalence of drug use by participants in this study was 6 times lower than the prevalence of AUDs. These data are distinct from North American MSM, who report high levels of drug use, especially club drugs that are associated with high HIV risk behaviors \[35\]. Our findings confirm the high prevalence of alcohol use from a recent trial that included MSM from Peru and the U. Among U. So, while it is important to design risk reduction intervention strategies aimed at lowering drug use, such strategies should be specifically targeted at the small subset of MSM that use drugs. Problematic alcohol use, on the other hand, is more widespread among MSM and in addition to individual-level interventions, should simultaneously be addressed as part of national HIV prevention interventions, including structural interventions that target the setting \[37\]. In light of the associations between AUDs and sexual risk behaviors, HIV risk reduction interventions should be developed to address not only sexual behavioral risks, but also alcohol consumption. Whereas current HIV prevention strategies do not ignore alcohol problems, most address it in a limited manner. It is therefore possible that problematic alcohol use negatively interferes with current evidence-based HIV prevention interventions that don't address alcohol problems. A multisite HIV Prevention Trials Network study that aimed to address alcohol use in the context of HIV risk behavior found that participants who showed signs of problematic alcohol use one year following the completion of alcohol use reduction interventions were more likely to relapse to having unprotected sex with multiple partners compared with those who remained completely alcohol-free after completing the intervention \[38\]. Given that a significant proportion of participants scored 20 or higher on the AUDIT, suggestive of meeting criteria for alcohol dependence, they should be referred to a specialist for diagnostic evaluation and treatment for dependent alcohol use, which can be effectively treated using evidence-based practices. Three medications are approved for the treatment of AUDs, including disulfiram, acamprosate \[24\] and both the oral and extended-release formulation of naltrexone. Disulfuram, through inhibition of aldehyde dehydrogenase, causes acute sickness e. It should be reserved only for highly motivated patients whose medication adherence is strictly observed. Both acamprosate and naltrexone reduce craving. In a large multisite trial, however, the use of naltrexone was superior to acamprosate either alone or in combination with weekly cognitive behavioral counseling sessions or combined with acamprosate \[39\]. Convenience samples recruited through a non-statistically determined referral chain mechanism may result in a non-representative sample of Peruvian MSM. Our study was cross-sectional, only allowing us to demonstrate high correlation, but not causality. Last, our study relied on self-report for alcohol and drug use and sexual risk behaviors. While concerns about social desirability response for culturally stigmatizing drug and alcohol use and sexual risk behaviors may result in under-reporting, the use of the anonymous CASI assessment and the remarkably high responses to these questions reduce these concerns. Notwithstanding these limitations, the large sample size and consistent and strong correlation between AUDs and drug use and validated sexual risk behaviors associated with HIV transmission suggest a relationship that is worthy of future intervention. These findings may, in part, explain the continued concentrated HIV epidemic among MSM and have important implications for HIV prevention, diagnosis and entry into and retention in care. These individuals would greatly benefit from strategies that reduce problematic drinking, including medication-assisted therapy, behavioral counseling and structural interventions. The authors gratefully acknowledge the subjects who gave their time to participate in this study, as well as the staff at Impacta and all other participating organizations and health centers throughout Peru for their involvement and dedication to the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. PLoS One. Find articles by Kaysia T Ludford. Find articles by Panagiotis Vagenas. Find articles by Javier R Lama. Find articles by Jesus Peinado. Find articles by Pedro Gonzales. Find articles by Rene Leiva. Find articles by Monica Pun. Find articles by Jorge Sanchez. Find articles by Frederick L Altice. Beatriz G J Grinsztejn : Editor. Received Mar 10; Accepted Jun 13; Collection date Open in a new tab. Percentages of non-missing data are shown. Click here for additional data file. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Less than minimum legal wage b. Self-reported sexually transmitted infections STI in the prior 12 months. Any drug use in past 3 months cocaine, pasta, amphetamines, marijuana, MDMA c , poppers.

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