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Research Effort Aims to Bring Personalized Medicine to Drug Prescriptions

The multi-center effort aims to revolutionize pharmacology by delivering a system to assess drug efficacy and tailor optimal drug treatment.

A Columbia University-led multicenter research effort called IndiPHARM: individual metabolome and exposome assessment for pharmaceutical optimization will develop a platform and monitoring system to prevent unwanted interactions between medications and other environmental, genetic, and lifestyle factors, in order to optimize therapeutic efficacy. IndiPHARM is supported by $39.5 million in funding from the Advanced Research Projects Agency for Health (ARPA-H), a federal research funding agency that supports transformative biomedical and health breakthroughs.

The IndiPHARM platform will be designed to measure hundreds of drugs and their metabolites and thousands of chemicals derived from the environment, diet, and lifestyles. Ultimately, the goal is to optimize how medications work by equipping individuals and their doctors with a tool that can answer the question, “Is the drug or combination of drugs I am taking optimized for me?” The platform will also help pharmaceutical suppliers, insurance payors, and providers to anticipate and reduce adverse therapeutic effects, including side effects and inefficiencies, in both individuals and populations.

“This project exemplifies how cutting-edge technologies and scientific collaborations across institutions and sectors can promote human progress and reduce suffering. IndiPHARM promises nothing less than to revolutionize pharmacology and patient care,” says Katrina Armstrong , MD, Interim President, Columbia University, and Chief Executive Officer, Columbia University Irving Medical Center.

Led by Gary Miller , PhD, Vice Dean for Research Strategy and Innovation and Professor of Environmental Health Sciences, at Columbia University Mailman School of Public Health, IndiPHARM also includes investigators from the Mayo Clinic, Harvard Medical School, Emory University, Brown University, and the Jackson Laboratory. The five-year ARPA-H agreement aims to catalyze a commercial venture.

“Medications have the potential to reduce suffering, alleviate symptoms, prevent serious events, and help people live longer and healthier lives. Unfortunately, there is a gap between what drugs are predicted to do and what they actually do in the real world,” says Miller, a globally recognized authority on the exposome. “IndiPHARM is marshaling the technology to bridge this gap.”

Doctors have more than 10,000 prescription drugs in their armamentarium, yet they lack basic information about how these drugs interact with each other and with an individual patient’s biology. Too often doctors and patients must resort to a costly, time-consuming, and sometimes dangerous process of trial and error to find the right medication or medication mixture, at the right dosage. According to the Agency for Healthcare Research and Quality, each year, adverse drug events (ADEs) account for nearly 700,000 emergency department visits and 100,000 hospitalizations .

Why do prescription drugs affect people differently? Individual differences in genetic composition explain only a small fraction of the variability. This suggests that non-genetic factors explain the varied and often suboptimal performance of medications. The field of exposomics, which is focused on measuring the physical, chemical, biological, and psychosocial influences that impact health, has matured to a point where it can help identify the varied factors that impede the effectiveness of a drug or combination of drugs. Miller notes, “As our teams developed the analytical methods for exposomics, we recognized that not only did we have the tools to measure thousands of environmental factors but also thousands of drugs and their metabolites, and that we could do it all at the same time.”

( In related news, this week, the National Institute of Environmental Health Sciences created a new national exposomics coordinating center led by Gary Miller. )  

The APRA-H funding will accelerate these efforts, which include extracting data from electronic health records, obtaining blood samples from well-characterized patients, automating sample prep, optimizing mass spectrometry protocols, streamlining data extraction and bioinformatics, and getting the tools into the clinic. The goal is to identify and prioritize drugs, drug classes, and exposure patterns that can be used to adjust or improve therapies.

By developing tests that can be used across dozens of health conditions, it should be possible to identify situations that interfere with drug therapy and adjust if needed. Are you a fast metabolizer of one of your medications? Are you taking the right dose? How do these drugs interact? Does your diet impact how your mediations work? Are the supplements you are taking interfering with your medications? Are the chemicals you are exposed to at work or in your neighborhood having an impact on your treatment? IndiPHARM will develop and validate a series of rapid, cost-effective tests that will make it possible to answer these questions.

The IndiPHARM team will start by focusing on metabolic conditions such as obesity, pre-diabetes, diabetes, fatty liver disease, and the common conditions that co-occur, including hypertension, high cholesterol, and depression. However, the platform could be used for nearly all human diseases and drug classes. The researchers will start by analyzing data from the LookAHEAD and ACCORD diabetes trials, the Tapestry study at Mayo Clinic, alongside electronic health records from the OHDSI database to identify relationships between drug therapy and treatment outcomes, as well as the complex physiologic states linked to sub-optimal therapy outcomes. Further ahead, they will apply their learnings to develop a test to predict drug efficacy and minimize adverse events.

The IndiPHARM team includes Columbia University (Miller, Randolph Singh, PhD, Serge Cremers, PhD, George Hripcsak, MD); Harvard Medical School (Chirag Patel, PhD); Mayo Clinic ( Konstantinos Lazaridis , MD, Arjun Athreya, PhD); Emory University (Doug Walker, PhD, Xin Hu, PhD, Dean Jones, PhD, Young-Mi Go, PhD); Brown University (Kurt Pennell, PhD); Jackson Laboratory (Shuzhao Li, PhD). Members of the team have been working together for over a decade with over 100 collaborative papers and multiple collaborative NIH grants.

The IndiPHARM team has a multifaceted strategy to commercialize the technology generated under the project. Consulting advisors and partners include Columbia Tech Ventures, AlleyCorp, Thermo Fisher, MBX Capital, Amazon Web Services, and others. IndiPHARM is funded through the ARPA-H  Health Science Futures Office.

Media Contact

Media contact:.

Tim Paul, [email protected]

Related Information

Meet our team, gary w. miller, phd.

• Vice Dean for Research Strategy and Innovation, Mailman School of Public Health
• Co-Director, Precision Medicine Core, Irving Institute
• Director, Center for Innovative Exposomics

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Alexander V. Kabanov , PhD

Adjunct Professor Director Mescal Swain Ferguson Distinguished Prof

Alexander V. Kabanov, Ph.D., Dr.Sci.

Director, center for nanotechnology in drug delivery, mescal swain ferguson distinguished professor, center for nanotechnology in drug delivery, adjunct professor, unc department of biomedical engineering, current projects, honors and awards.

Alexander “Sasha” Kabanov, Ph.D., D.Sc., is the Mescal S. Ferguson Distinguished Professor and director of the  Center for Nanotechnology in Drug Delivery  at the UNC Eshelman School of Pharmacy and co-director of the  Carolina Institute for Nanomedicine  at the University of North Carolina at Chapel Hill.

Kabanov began his academic journey at M. V. Lomonosov Moscow State University (MSU), where he graduated in 1984. He continued his studies at the same institution, earning a Ph.D. in 1987 and a D.Sc. in 1990. His scientific career took root in the Soviet Union and later transitioned to the United States. From 1994 to 2012, Kabanov was affiliated with the University of Nebraska Medical Center in Omaha, Nebraska. During his tenure there, he established the first academic nanomedicine center in the United States in 2004.

In 2012, Kabanov moved to the University of North Carolina at Chapel Hill where his research focuses on several key areas.

• Polymeric Micelles : Kabanov co-developed the first polymeric micelle drug that entered clinical trials for cancer treatment, thereby establishing polymeric micelles as a clinically approved drug delivery platform.
• Polyplexes : Kabanov was among the first to use polycations and later, cationic block copolymers for delivering nucleic acids into cells. He evaluated core-shell polyelectrolyte complexes of nucleic acids and polypeptides, now known as “polyplexes”, for therapeutic drug and gene delivery.
• Nanogels, Nanoparticle-Macrophage Carriers, and Exosomes : These have been utilized for delivering small drugs, nucleic acids, and polypeptides to treat cancers and diseases of the central nervous system.

Kabanov is a highly cited researcher, with over 340 scientific papers (garnering over 50,000 citations, and a Google h-index greater than 115), 36 US patents, and has co-founded several pharmaceutical companies. His cumulative research support in academia has been over $120 million.

Kabanov has mentored more than 80 graduate students and postdocs, half of whom are women and underrepresented minorities. Nineteen past members of Kabanov laboratory hold faculty appointments. He is the director of the NCI’s T32 training program in Cancer Nanotechnology .

Kabanov also established symposium series in nanomedicine and drug delivery , chaired Gordon Research Conferences, and received numerous honors and awards, including the Lenin Komsomol Prize, NSF Career award, George Gamow award, and the Controlled Release Society (CRS) Founders award.

Kabanov is an elected member or fellow of prestigious academies and organizations, including Academia Europaea, Russian Academy of Sciences, National Academy of Inventors, American Association for the Advancement of Science, American Institute for Medical and Biological Engineering, and CRS. He has served as the past President and current CEO of the Russian American Science Association, director-at-large for CRS (2019-2022), and chair of the CRS College of Fellows sub-committee (2022-2023).

Education, Certification and Licensure

• 1990: Doctor of Chemical Sciences (D.Sc.) in Chemical Kinetics and Catalysis and Biochemistry at Moscow State University
• 1984 – 1987: Candidate of Chemical Sciences (Ph.D. equivalent) in Chemical Kinetics and Catalysis at Moscow State University
• 1979 – 1984: Diploma with distinction (M.S. equivalent) in Chemistry at Moscow State University

Courses and Lectures

DPMP 862/863 “Special Topics in Advanced Pharmaceutics” 3 cr.

Office Hours

By appointment only

Google Scholar

Lab Website

Twitter @alkabanov

ORCID iD: 0000-0002-3665-946X

• Carolina Cancer Nanotechnology Training Program (C-CNTP)
• Towards Translation of Nanoformulated Paclitaxel-Platinum Combination
• Extracellular Vesicles for CNS Delivery of Therapeutic Enzymes to Treat Lysosomal Storage Disorders
• Cell-based Platform for Gene Delivery to the Brain

Highly Cited Researcher: Thompson Reuters/Clarivate Analytics – Pharmacology & Toxicology (2014, 2018, 2021)

Huang, Kabanov and Roth Recognized for Research Influence

Three faculty members from the UNC Eshelman School of Pharmacy were recognized on the Clarivate Analytics list of Highly Cited Researchers for 2018. Leaf Huang, Ph.D., Alexander Kabanov, Ph.D., Dr.Sci., and Bryan Roth, Ph.D., M.D., were among 6,000 scientists worldwide … Read more

Kabanov Named President of Russian-American Scientists Association

Alexander Kabanov, Ph.D., Dr.Sci., assumed office as president of the Russian-American Scientists Association (RASA-America) on Nov. 5. Kabanov is the Mescal S. Ferguson Distinguished Professor and director of the Center for Nanotechnology in Drug Delivery at the UNC Eshelman School of Pharmacy and … Read more

Kabanov Elected 2018 Controlled Release Society Fellow

Alexander “Sasha” Kabanov, Ph.D., Dr. Sci., has been selected for membership in the College of Fellows of the Controlled Release Society for his “outstanding contributions to the field of delivery science and technology.” Kabanov will be inducted into the college … Read more

Kabanov Receives TBJ Life Sciences Award

Alexander “Sasha” Kabanov, Ph.D., Dr. Sci., is a recipient of a 2018 Life Sciences Award from the Triangle Business Journal. Kabanov was nominated in the category of Outstanding Individual Research from Universities or Research Institutes. The award was presented at … Read more

Third Carolina Nanoformulation Workshop Shares Discoveries in Nanomedicine

From March 12 to 16, scientists from industry and academia came together at the UNC Eshelman School of Pharmacy to learn about the latest advances in nanomedicine and to get hands-on experience with advanced nanoformulations at the third annual Carolina … Read more

Kabanov to Lead Russian-American Science Society

Alexander “Sasha” Kabanov, Ph.D., Dr.Sci., is the president-elect of the Russian-American Science Association. Kabanov was elected to his new post at the organization’s annual meeting at Northwestern University in Chicago on Nov. 4 and 5, where he also received the … Read more

Kabanov Elected to National Academy of Inventors

Alexander “Sasha” Kabanov, Ph.D., Dr.Sci., Mescal Swaim Feruguson Distinguished Professor at the UNC Eshelman School of Pharmacy, has been named a Fellow of the National Academy of Inventors, the organization announced Tuesday. Kabanov is the director of the School’s Center … Read more

Kabanov Meets with President of Armenia

Alexander “Sasha” Kabanov, Ph.D., met with the president of Armenia on Nov. 8 as part of a group of participants in the second All-Armenian Scientific Conference held in the capital city of Yerevan on November 5-8. The delegation consisted of … Read more

Postdoc Elizabeth Wayne Reflects on TED Experience

Elizabeth Wayne, Ph.D., a postdoctoral fellow studying how immune cells can be used to fight cancer, gave a TED talk on the main stage at TED 2017 in Vancouver, Canada. Wayne was announced as a TED fellow in January 2017. … Read more

Yuhang Jiang Wins UNC Grad School Impact Award

Yuhang Jiang, Ph.D., a December 2016 graduate of the pharmaceutical sciences doctoral program at the UNC Eshelman School of Pharmacy, has received a 2017 Horizon Award from the UNC Graduate School for his research into a treatment to repair the … Read more

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• FDA-CDER and HESI | Nitrosamine Ames Data Review and Method Development Workshop - 10/15/2024

Public | In Person

Event Title FDA-CDER and HESI | Nitrosamine Ames Data Review and Method Development Workshop October 15 - 16, 2024

FDA White Oak Campus, Room 2031, Building 2. 10903 New Hampshire Avenue, Silver Spring.

Background:

The Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and Health & Environmental Sciences Institute (HESI) Global agree to co-sponsor the Nitrosamine Ames Data Review and Method Development Workshop that convenes subject matter experts to review data and discuss recommended test conditions for the Enhanced Ames Testing for nitrosamines. Both FDA and HESI have a mutual interest in addressing this scientific problem and publicly disseminating scientific knowledge under the terms set out below. 

This workshop will review the nitrosamines Ames data generated by the US Food and Drug Administration/National Center for Toxicological Research (US FDA/NCTR), European Medicines Agency’s (EMA) MutaMind project and through the collaborative HESI Genetic Toxicology Technical Committee (GTTC) ring trial, each of which have been testing nitrosamine compounds across various Ames assay conditions. Key aspects of the Ames assay as it pertains to nitrosamines will be addressed through data presentations and panel discussions from these three research programs and additional invited speakers.

Goals and Objectives:

• To provide a forum for open discussion between regulators and industry on the data generated using enhanced Ames assay methodologies to assess the mutagenic potential of nitrosamines.
• Present and hold open discussions on specific questions related to the generated data.
• Discuss recommendations on the relevant and most predictive test conditions of the Ames test for more reliable prediction of the mutagenic potential of nitrosamines.
• Discuss the correlation of Ames assay results for nitrosamine drug substance related impurities (NDSRIs) and in vivo carcinogenicity/mutagenicity.
• Generate recommendations for publication in a scientific journal and make them publicly available.

Who Should Attend:

This workshop is intended for scientists from organizations (EMA, FDA, HESI, Industry, Contract Research Organizations) and from other Regulatory Agencies who have been directly involved in generating and evaluating Ames assay data for nitrosamines across various assay conditions. The primary audience includes leading academic experts, interested pharmaceutical companies, regulatory agencies, non-profit organizations, scientists involved in the assessment of nitrosamine impurities in those same industries, and regulatory scientists who have conducted research on Ames assay assessment of nitrosamines or who evaluate this data.  Attendance is limited to invited participants involved in generating data related to enhanced Ames testing.

If to HESI:           

Connie Chen, Senior Scientific Program Manager Health & Environmental Sciences Institute (HESI) 740 15th Street NW, Suite 600 Washington, DC 20005 Tel: 202-652-8404

Aisar Atrakchi, Supervisor Pharmacology Toxicology CDER/Office of New Drugs Food and Drug Administration 10903 New Hampshire Avenue White Oak Building 22 Silver Spring, MD 21029 Tel: 301-796-1036 Email:  [email protected]

Timothy J. McGovern, Associate Director, Pharmacology/Toxicology CDER/Office of New Drugs Food and Drug Administration 10903 New Hampshire Avenue White Oak Building 22 Silver Spring, MD 21029 Tel: 240.402.0477 Email: [email protected]

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Cancer biomarkers testing in Russia: implementation issues and ways to improve

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G Mishurovskiy, D Meretukov, A Glushenko, A Kravchenko, E Kakorina, Cancer biomarkers testing in Russia: implementation issues and ways to improve, European Journal of Public Health , Volume 31, Issue Supplement_3, October 2021, ckab165.363, https://doi.org/10.1093/eurpub/ckab165.363

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In 2019 Russian Ministry of Health launched the federal program “Oncology”. Its main goals include an increase of 5-year cancer patient survival up to 60% or more by 2024. An improvement in survival may be achieved by prescribing innovative cancer drug regimens, which require prior molecular diagnosing. Healthcare in Russia is state-funded and every constituent territory defines the list of molecular tests available and their costs independently. The aim research was to perform a comparative analysis of molecular testing costs and availability in all 85 units of Russia.

The data for the research was obtained from the rate agreements of Territorial Compulsory Medical Insurance Funds of each territory, available online. The list of biological markers analyzed was based on local guidelines and included EGFR, ALK, ROS1, BRAF, KRAS/NRAS, BRCA1/2, HER2, PD-L1 and MSI.

At the time of research, only 50 territories had all tests included in the rate agreements. 35 territories had only some of these tests available or stated the availability of “molecular diagnostics” with a fixed cost for any test falling into this category. The titles and costs of same molecular tests varied between different territories with up to 10-fold difference in cost for certain tests. The mean number of tests planned for payment by the state was 7 per 10,000 population per year, though the estimated number of tests required is 17.4 per 10,000 population per year.

Our research revealed significant variation in molecular testing naming, availability and costs. This complicates planning and funding of cancer diagnostics programs and obstructs the process of drug prescription, making it difficult to achieve an improvement in patient survival. The situation could be amended by the development of standardized test naming and cost calculation.

Almost half of Russia’s constituent territories have legal obstructions to perform some or every of essential oncological molecular tests, which hinders improvement in survival of cancer patients.

The naming and cost calculation of molecular tests in Russia’s Territorial Insurance Funds are not standardized, causing inadequate funding and reduced availability of molecular diagnosing.

• fixed costs
• antineoplastic agents
• biological markers
• brca1 protein
• genes, erbb-2
• health insurance
• medical oncology
• molecular diagnostic techniques
• prescriptions, drug
• epidermal growth factor receptors
• receptor, erbb-2
• tumor markers, biological
• principles of law and justice
• k-ras oncogene
• ros protein
• prescribing behavior
• naming function
• programmed cell death 1 ligand 1

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Investigational drug branch (idb), idb oversees an innovative early therapeutics clinical research program., idb collaborates with academia and industry through an nci-funded program to carry out the clinical evaluation of novel anti-cancer agents..

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• NExT is the program in the NCI Developmental Therapeutics Program that selects agents for NCI-sponsored pre-clinical and clinical development
• The Experimental Therapeutics Clinical Trials Network (ETCTN) is the clinical trials network administered through the IDB that performs clinical studies of the agents that are approved through NExT. Dr. Percy Ivy is the Program Director for the ETCTN and Kim Witherspoon is the Senior Program Specialist.

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Evaluation of antibiotic susceptibility of Bacteroides, Prevotella and Fusobacterium species isolated from patients of the N. N. Blokhin Cancer Research Center, Moscow, Russia

Affiliations.

• 1 N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse, 24, 115478 Moscow, Russian Federation. Electronic address: [email protected].
• 2 N. N. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse, 24, 115478 Moscow, Russian Federation.
• PMID: 25157873
• DOI: 10.1016/j.anaerobe.2014.08.003

In total 122 non-duplicate Bacteroides, Prevotella and Fusobacterium spp isolated from cancer patients between 2004 and 2014 were involved in this study. Most of the strains belonged to the B. fragilis group (55%), followed by Prevotella strains (34.4%) and Fusobacterium spp (10.6%). The species identification was carried out by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and they were identified on species level with a log (score) >2.0. The most common isolates were B. fragilis, B. thetaiotaomicron, B. ovatus and B. vulgatus. Among Prevotella species, the most frequently isolated species were P. buccae, P. buccalis, P. oris, P. denticola and P. nigrescens, and most of the Fusobacterium spp. were F. nucleatum. Susceptibilities of the strains were determined by the E-test methodology. The percentage of the susceptibility of B. fragilis group isolates were: metronidazole (MIC ≤4 μg/ml), 97%; imipenem (MIC ≤2 μg/ml), 95.5%; amoxicillin/clavulanate (MIC ≤4 μg/ml), 95.5% and clindamycin (MIC ≤4 μg/ml), 77.6%. Three B. fragilis isolates proved to be multidrug-resistant (parallel resistance to imipenem, amoxicillin/clavulanate and metronidazole or clindamycin was observed). All Prevotella strains tested were susceptible to imipenem and amoxicillin/clavulanate, whereas 78.6% of the pigmented Prevotella species and 46.4% of the non-pigmented species were resistant to penicillin (MIC >0.5 μg/ml). The susceptibility to metronidazole and clindamycin were 93% and 88%, respectively. All Fusobacterium strains were sensitive to all tested antibiotics, including penicillin.

Keywords: Antimicrobial susceptibility; Bacteroides; Cancer patients; Fusobacterium; Prevotella; Resistance.

Copyright © 2014 Elsevier Ltd. All rights reserved.

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• Open access
• Published: 11 January 2024

HIV knowledge, self-perception of HIV risk, and sexual risk behaviors among male Tajik labor migrants who inject drugs in Moscow

• Casey Morgan Luc   ORCID: orcid.org/0000-0003-3669-9821 1 ,
• Judith Levy 1 ,
• Mahbat Bahromov 2 ,
• Jonbek Jonbekov 2 &
• Mary E. Mackesy-Amiti 1  

BMC Public Health volume  24 , Article number:  156 ( 2024 ) Cite this article

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The interplay of human immunodeficiency virus (HIV) knowledge and self-perception of risk for HIV among people who inject drugs is complex and understudied, especially among temporary migrant workers who inject drugs (MWID) while in a host country. In Russia, Tajik migrants make up the largest proportion of Moscow’s foreign labor. Yet, HIV knowledge and self-perceived risk in association with sexual risk behavior among male Tajik MWID in Moscow remains unknown.

This research examines knowledge about HIV transmission, self-perception of HIV risk, and key psychosocial factors that possibly contribute to sexual risk behaviors among male Tajik labor MWID living in Moscow.

Structured interviews were conducted with 420 male Tajik labor MWID. Modified Poisson regression models investigated possible associations between major risk factors and HIV sexual risk behavior.

Of the 420 MWID, 255 men (61%) reported sexual activity in the last 30 days. Level of HIV knowledge was not associated in either direction with condom use or risky sexual partnering, as measured by sex with multiple partners or female sex workers (FSW). Lower self-perceived HIV risk was associated with a greater likelihood of sex with multiple partners (aPR: 1.79, 95% CI: 1.34, 2.40) and FSW (aPR: 1.28, 95% CI: 1.04, 1.59), but was not associated with condom use. Police-enacted stigma was associated with sex with multiple partners (aPR: 1.22, 95% CI: 1.01, 1.49) and FSW (aPR: 1.32, 95% CI: 1.13, 1.54). While depression and lower levels of loneliness were associated with condomless sex (aPR: 1.14, 95% CI: 1.05, 1.24; aPR: 0.79, 95% CI: 0.68, 0.92, respectively), only depression was associated with condomless sex with FSW (aPR: 1.26, 95% CI: 1.03, 1.54).

Conclusions

HIV prevention programing for male Tajik MWID must go beyond solely educating about factors associated with HIV transmission to include increased awareness of personal risk based on engaging in these behaviors. Additionally, psychological services to counter depression and police-enacted stigma are needed.

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Introduction

Research has shown that labor migration from low to high human immunodeficiency virus (HIV) prevalence countries is associated with increased risk of HIV infection for migrant workers [ 1 , 2 ] This risk is further heightened among migrants who inject drugs (MWID) while in the host country [ 3 ]. In Russia, a country with high HIV prevalence [ 4 ], HIV risk for MWID is exacerbated by disparities in the availability and provision of HIV prevention and treatment services for labor migrants [ 3 , 5 , 6 , 7 ]. In addition, MWID are impacted negatively by Russian policing practices that focus on enforcing petty criminal justice penalties for migrants in general and toward MWID in particular through physical harassment and syringe confiscation to discourage drug use. Such practices hinder harm reduction efforts and create barriers for MWID in accessing services for the prevention, treatment and care of HIV [ 8 , 9 ].

This research presents findings on the prevalence and correlates of HIV sexual risk behavior among male Tajik MWID who are temporarily living and working in Moscow. While in Moscow, MWID experience the “double jeopardy” of social marginalization due to their dual status as a migrant and injection drug user, both of which are thought to increase sexual risk for HIV [ 3 , 10 ]. Meanwhile, HIV knowledge and HIV risk perception have been found to influence sexual risk behavior among those who inject drugs [ 11 , 12 ], but the interplay of these two factors on sexual risk behavior is complex [ 13 ], and less understood among people who inject drugs (PWID). One cross-sectional study conducted with PWID in Iran found that HIV risk perception modified the association between HIV knowledge and sexual risk behavior, but the study sample was small and not generalizable [ 14 ]. A separate cross-sectional study partly comprised of PWID in Iran identified a “relatively good” level of comprehensive knowledge of HIV and acquired immunodeficiency syndrome (AIDS), but the prevalence of HIV risk perception was low while sexual risk behavior was high [ 15 ]. These findings suggest that engaging in risky sexual behavior may be best explained by self-perception of being at HIV risk rather than degree of HIV knowledge alone. Whether through effect modification or not, the relationship between HIV risk perception and HIV knowledge on sexual risk behavior has yet to be investigated and reported in the scientific literature among MWID.

In addition, psychosocial factors appear to influence sexual risk behavior among PWID while possibly playing a role in promoting sexual risk behavior among MWID [ 11 , 12 , 15 ]. Stigma has been well-documented to undermine progress towards ending the global HIV/AIDS epidemic, but the complexity of intersectional stigma calls for research to better measure and contextualize stigma in separate global populations [ 16 ]. Due to the experience of aggressive policing tactics and harassment, migrants are particularly prone to police-enacted stigma that may form a “driving force” towards HIV sexual risk behavior [ 17 , 18 , 19 ], but this has yet to be measured among MWID. Additionally, migrant-related stressors including both loneliness and depression have been linked to HIV risk behavior [ 20 , 21 , 22 ]. Among Tajik MWID, poor working and living conditions, loneliness due to separation from family and friends at home, and Tajik gender constraints to condom use all reflect the general emotional stress common to temporary migrant laborers in diaspora and an increased vulnerability to HIV through engaging in risky sexual behavior [ 5 , 6 , 23 ]. Examining factors associated with sexual risk behaviors among male Tajik MWID as an understudied population may help to inform prevention strategies for successfully addressing their sexual risk while adding to a better scientific understanding of the relationship between these key factors and risky sexual behavior.

The research design and procedures of this study were reviewed and approved by the institutional review boards of the University of Illinois Chicago, PRISMA Research Center, and the Moscow Nongovernment Organization, “Bridge to the Future.” The analysis is based on data collected at baseline for a clinical trial assessing the efficacy of the “Migrants’ Approached Self-Learning Intervention in HIV/AIDS for Tajiks” (MASLIHAT) peer-education model in reducing HIV risk behavior among Tajik MWID while living in Moscow.

Recruitment

From October 2021 to April 2022, 140 male Tajik migrant workers who inject drugs were recruited from 12 sites in Moscow: 2 Tajik diaspora organizations, 4 bazaars, and 6 construction work sites. To be eligible to participate in the research, prospective participants had to be a male Tajik migrant aged 18 or older, a current or former PWID, give written informed consent, intend to reside in Moscow for the next 12 months to permit completing baseline and four follow-up interviews, and willing to recruit two male Tajik migrants who inject drugs for interviewing as PWID network members. Network members ( n  = 280) had to meet the same eligibility criteria as the migrant who referred them but also: 1) have injected drugs at least once in the last 30 days; and 2) be someone whom the referring migrant sees at least once a week to facilitate sharing MASLIHAT HIV prevention information. The analysis draws on data collected from the study’s sample of 420 male Tajik MWID in Moscow at enrollment (baseline) prior to their random assignment to one of two research intervention conditions.

Data collection

After giving informed consent, participants were interviewed at the PRISMA office in Moscow or a private location of their choosing. A structured questionnaire collected information on participants’ sociodemographic characteristics, HIV-related knowledge, HIV risk perception, substance use and sexual risk behavior, experience with police-enacted stigma, and psychosocial measures of depression and loneliness. Participants received the customary compensation in Moscow of $20.00 for their time and transportation costs in being interviewed .

Demographic information consisted of age (years), marital status (currently married, not married/divorced), and highest educational attainment (primary school/secondary school, some university education/higher).

HIV knowledge was assessed by responses to 8 statements as being either “safe” or “unsafe” in the possibility of HIV transmission such as “being bitten by mosquitoes or other insects” and 5 statements as either “true” or “false” in terms of becoming infected such as “there is a test to determine if a person has HIV.” Responses were coded as either correct or incorrect with “don’t know” coded as incorrect. Correctly answered items were summed for a possible final score per individual between 0 – 13 (Cronbach’s alpha: 0.91). Low HIV knowledge was defined as scoring from 0 – 6 and moderate/high as scoring from 7–13.

Self-perception of HIV risk was assessed with two items: 1) “How likely are you to get HIV?” on a scale from “not at all likely” (0) to “very likely” (3). 2) How much do you worry about HIV?” from “not at all” (0) to a lot (2). A self-perceived HIV risk score was created per person by summing the responses to both items with scores ranging from 0—5. Low HIV risk perception was defined as a score of 0 or 1 and moderate/high as scoring between 2–5.

HIV sexual risk behavior was measured with three items: number of female sex partners, sex with female sex workers (FSW), and engaging in condomless sex. To assess possible HIV risk behavior through sexual partnering, participants were asked how many women and the number of FSW with whom they had sexual intercourse in the past 30 days. Number of female sex partners was coded as: 0 or 1 sex partner = 0 (little to no risk) or ≥ 2 sex partners = 1 (some level of risk). Sex with FSW was coded as: 0 FSW = 0 (no sexual intercourse reported with FSW) or ≥ 1 FSW = 1 (Sex with FSW). To assess frequency of engaging in sex without a condom: participants were asked, “how often did you use a condom when having sexual intercourse?” for each of three partner categories: “regular female partner in Russia,” “Moscow FSW,” and “other sexual partners not engaged in selling sex.” Response categories were “never,” “sometimes,” “often,” or “always.” Responses of “always used a condom” for all three partner categories were categorized as “engaging in sex with condoms.” Otherwise, responses were categorized as engaging in condomless sex. The items were combined to create a binary measure of “any condomless sex” vs. “sex with condoms” in the past 30 days.

Psychosocial measures

Symptoms of depression were measured using the 20-item Center for Epidemiologic Studies Depression scale—revised (CESD-R) (Cronbach’s alpha: 0.91) [ 24 , 25 ]. Based on the total score as calculated by the sum of item responses and responses to select items, a depression score was created with five ordinal categories: 1) no clinical significance, 2) subthreshold depression symptoms, 3) possible major depressive episode, 4) probable major depressive episode, and 5) meets criteria for major depressive episode. Loneliness was measured using the 20-item UCLA loneliness scale and a loneliness score was calculated as the mean of item responses (Cronbach’s alpha: 0.94) [ 26 ].

Police-enacted stigma was measured by responses ranging from “never” (0) to “very often” (4) to each of three statements: “I have been hassled by the police because I’m a migrant,” “I have been detained by the police because I’m a migrant,” and “I have been beaten by the police because I’m a migrant.” A summation score of experience with police-enacted stigma was calculated per participant ranging from 0–12.

A population-averaged modified Poisson regression analysis was conducted with a sandwich estimator of variance and exchangeable within-group correlation structure for network clusters to obtain adjusted prevalence ratios (aPR) with their 95% confidence intervals (95% CI) [ 27 ]. Adjusting for demographic and psychosocial factors that might impact HIV sexual risk behavior, multivariable modeling was used to examine associations between HIV knowledge and HIV risk perception and four sexual risk outcomes: sex with multiple partners (model 1), sexual activity with one or more FSW (model 2), condomless sex (model 3) and condomless sex with FSW (Model 4). To test the possible moderating effect of HIV risk perception on the relationship between HIV knowledge and sexual risk behavior, the analysis tested for both the separate and interactive effects of HIV knowledge and perception of HIV risk on each sexual outcome. The analyses were performed using Stata software (v. 18) [ 28 ].

Table 1 presents both the demographic characteristics of the total sample and the subsample of participants reporting sexual activity in the 30 days prior to being interviewed. The total sample of 420 participants was on average 30 years of age, not married/divorced, and at a secondary school education level. No significant differences were found between the demographic characteristics of men recruited through worksites, bazaars, and non-governmental organizations (NGO) versus those whom they referred to the study as network members with the exception that the latter on average were one year younger (B = -1.07, 95% CI -1.69 – -0.46) and more likely to be on their first labor migration trip (Wald χ 2  = 7.49, p  = 0.02).

• Sexual risk behavior

Of the total 420 participants in the study sample, 60.7% (255) reported having been sexually active in the last 30 days prior to being interviewed. Of these, 124 men (48.6%) reported having sex with multiple partners, 177 (69.4%) reported sex with one or more FSW, and 178 (69.8%) reported engaging in sex without a condom including 62 men (35%) who did not use one when having sex with FSW.

HIV knowledge

Thirty-two percent of participants ( n  = 136) scored low on HIV knowledge. Of the 88 sexually active men who also scored low on HIV knowledge, 45 (51.1%) reported having multiple partners, 62 (70.5%) reported sex with FSW, and 61 (69.3%) reported engaging in condomless intercourse including 22 participants who reported not having used one with FSW. Comparing those with low to moderate/high HIV knowledge scores, sexual risk behavior was not significantly different. Of the 167 sexually active men who scored moderate/high on HIV knowledge, 79 (47.3%) reported having multiple partners, 115 (68.9%) reported sex with FSW, and 117 (70.1%) reported engaging in condomless sex including 40 men who reported sexual activity with FSW.

Self-perception of HIV risk

Forty-five percent of participants ( n  = 189) perceived themselves to be at low risk for HIV. Of the 123 sexually active men who also perceived themselves to be at low HIV risk, 82 (66.7%) reported having multiple sex partners, 97 (78.9%) reported sexual activity with FSW, and 83 (67.5%) reported engaging in condomless sex including 39 men who reported sexual activity with FSW. Comparing those with low to moderate/high HIV risk perception scores, reporting multiple sex partners and reporting sexual activity with FSW were significantly different ( P  < 0.05), but reporting engaging in condomless sex including condomless sexual activity with an FSW were not significantly different. Of the 127 sexually active men who also perceived themselves to be at moderate/high HIV risk, 39 (30.7%) reported having multiple sex partners, 75 (59.1%) reported sexual activity with FSW, and 92 (72.4%) reported engaging in condomless sex including 21 men who reported sexual activity with FSW.

Multivariable analyses

All study participants for whom there were complete data were included in the multivariable modeling of factors associated with engaging in sexual risk. Table 2 shows the adjusted prevalence ratios of each sexual risk behavior. Model 1 and 2 examine the association between key variables and engaging in sex with multiple sex partners and with FSW. Low HIV risk perception was associated with a 79% higher prevalence of multiple sex partners (aPR: 1.79, 95% CI: 1.34, 2.40, Table  2 ) and a 28% higher prevalence of sexual activity with FSW (aPR: 1.28, 95% CI: 1.04, 1.59) when compared to those with moderate/high HIV risk perception. Older age was associated with a lower prevalence of multiple sex partners (aPR: 0.87, 95% CI: 0.84, 0.91) and sexual activity with FSW (0.91, 95% CI: 0.88, 0.94). A one-unit increase in depression scoring was associated with a 19% lower prevalence of multiple sex partners (aPR: 0.81, 95% CI: 0.65, 1.01). Conversely, a one-unit increase in police-enacted stigma score was associated with a 22% greater prevalence of multiple sex partners (aPR: 1.22, 95% CI: 1.01, 1.49) and a 32% greater prevalence of sexual activity with FSW (aPR: 1.32, 95% CI: 1.13, 1.54).

Model 3 and Model 4 investigate condomless sex generally as well as specifically with FSW. Neither knowledge of how HIV is transmitted, nor HIV risk perception were significantly associated with condomless sex or condomless sex with FSW. Meanwhile, higher levels of loneliness were associated with less likelihood of engaging in condomless sex (aPR: 0.79, 95% CI: 0.68, 0.92), while a one-unit increase in depression score was associated with a 14% higher likelihood of engaging in condomless sex (aPR: 1.14, 95% CI: 1.05, 1.24) and a 26% higher likelihood of engaging in condomless sex with FSW specifically (aPR: 1.26, 95% CI: 1.03, 1.54).

The joint effect of HIV knowledge and HIV risk perception on each sexual risk outcome is shown in Table  3 . No evidence of an additive interaction between HIV knowledge and HIV risk was found. When low HIV risk perception was present, however, the prevalence of multiple sex partners, sexual activity with FSW, and condomless sex with FSW was higher. However, significant moderating effects were only found for multiple sex partners.

To the best of our knowledge, this is the largest cross-sectional study to examine the factors that may influence HIV sexual risk behavior among male Tajik MWID, a highly understudied population at-risk for HIV [ 29 ]. Prevalence of HIV sexual risk behavior among this migrant population is high as evidenced by the number of men engaging in sex with multiple partners (48.6%) and sex without a condom (69.8%) including with FSW (35.0%). Of the total study sample, 32.4% scored low on HIV knowledge and 46.1% on self-perceived HIV risk. The prevalence of HIV sexual risk behavior in this study sample is consistent with a cross-sectional study among male Tajik migrants in Moscow [ 30 ], but higher than a second study that included both Eastern European and Central Asian (EECA) male labor migrants in Moscow [ 31 ]. In this cross-sectional study, thirty percent of migrants reported multiple female partners and condom use ranged from 35 to 52% [ 31 ]. Possibly due to male Tajik gender norms and/or other challenges unique to the Tajik migrant experience in Moscow [ 23 ], male Tajik migrants, especially male Tajik MWID, may have greater sexual risk for HIV acquisition than their EECA counterparts [ 3 ].

Prevention programs for at-risk populations typically build on the assumption that knowledge of which sexual activities carry HIV risk is needed to reduce or end high risk behavior [ 32 , 33 ]. Yet, the study’s finding that HIV knowledge was not associated with engaging in risky sexual behavior suggests that providing male Tajik migrants with HIV risk-reduction education alone likely would prove ineffective. Meanwhile, low self-perceived risk for HIV was found to be associated with greater likelihood of engaging in risky sexual activity as indicated by multiple partners and condomless sex including with FSW. Analysis of the possible joint influence of HIV knowledge and self-perceived risk for HIV on risky sexual behavior failed to support an interaction effect. These findings suggest the role of self-perceived HIV risk over HIV knowledge as a significant factor influencing sexual risk behavior. These findings are critical as the scope of prevention work in Moscow is often restricted to bolstering individual knowledge and behaviors through peer education interventions. This is due to the lack of access of preventive services, such as pre-exposure prophylaxis and methadone, and citizen requirements needed for accessing HIV care in Russia [ 10 , 34 ], HIV prevention programming designed to raise Tajik migrants’ and possibly other vulnerable populations’ awareness of being at personal risk is particularly needed to strengthen the effects of HIV preventive interventions.

As for psychosocial-related factors, police-enacted stigma was associated with sexual activity with multiple sex partners and FSW in the last 30 days whereas depression was associated with condomless sex both in general and specifically with FSW. These findings add to the documented role of both police-enacted stigma and depression to be associated with HIV sexual risk behavior among Tajik labor migrants [ 35 , 36 , 37 , 38 ]. To contextualize intersectional stigma, effective HIV prevention programming among Tajik labor migrants should specifically aim to alleviate the pressure of police aggression and harassment on overall wellbeing, consistent with a separate study that recognizes the role of policing in HIV prevention programming among labor migrants [ 17 ]. In addition to police-enacted stigma, depression may largely be explained by the overall challenges of migrant life in Russia [ 8 , 23 , 31 ]. However, loneliness was associated with a lower prevalence of condomless sex among sexually active male MWID, contrary to the documented role of loneliness as a sexual risk factor among migrant populations [ 20 , 38 ]. Possibly among male migrants who are not sexually active and/or experience loneliness, these negative feelings can manifest themselves in either the decreased likelihood of engaging in any sexual activity or more protective attitudes towards sex. The correlation of these psychosocial factors with risky sex calls attention to the need for HIV prevention programming that helps to address the stress and psychosocial challenges of migrant life. Additionally, the prevalence of all psychosocial variables as reported in Table  1 was marginally higher among men who disclosed not having engaged in sex versus those who were sexually active during the same 30-day period. The similarity between the two sub-populations suggests that Tajik migrants in general are subject to emotional distress that can negatively affect their daily lives.

Limitations

The study’s analysis of the prevalence and correlates of risky sex focuses solely on those who reported sexual activity and excludes those men who reported being sexually inactive. It may be that some unknown number of the study’s sexually inactive participants purposely abstained from sex to avoid HIV, but the study’s data do not include inquiry into this possibility. Also, neither of the two measures used in asking participants to assess their personal risk for HIV specified that this calculation should be based solely on sexual risk. Given that the study’s sample is composed entirely of PWID, some proportion of participants may have factored in personal risk for HIV through both sex and injection drug use. While this likelihood doesn’t mitigate the validity of the study’s findings derived by examining the association between self-perceived risk for HIV and engaging in risky sexual behavior, it does not allow assessment of how much drug use alone may contribute to Tajik MWID’s self-perception of being at HIV risk.

In terms of sampling, the study’s initial participants were obtained through in-person recruitment at 10 occupational sites and by referral from 2 Tajik service networks. Each of these participants, in turn, recruited two active MWID participants through their social networks. Consequently, the results of the study may not generalize to those migrants whom these methods failed to reach or who chose not to participate. Furthermore, the study’s measures of sexual risk behavior focus solely on unsafe sex with female sexual partners. It is quite possible that acts of unsafe sex with another male also may have occurred during the same 30-day period. Same-sex behavior is highly stigmatized and considered morally unacceptable within the male Tajik migrant community, and it is unlikely that its occurrence would be disclosed by a participant during an initial interview. Asking a male Tajik about possibly having engaged in same-sex behavior is sufficiently affrontive culturally that it carries the potential risk of triggering the participant’s decision to end the interview. Consequently, measures of sexual risk in the study are confined solely to unsafe sex with female partners.

For the multivariable analysis, differences in findings between models may be partly explained by the differences in sample sizes; the sample of those who report sexual activity, and specifically sexual activity with FSW, may differ from the overall sample. Model 3 and Model 4 are subject to a lower precision due to a smaller sample compared to Model 1. This is evident in the assessment for the moderating effect of HIV risk perception as both Model 1 and Model 4 noted a similar increase in magnitude for the respective outcomes (multiple sex partners and sexual activity with FSW) when HIV risk perception was low, but only Model 1 was significant. Finally, the study’s baseline data are cross-sectional and only examined HIV risk behavior in the last 30 days. They cannot provide information about how variables of interest may have differed prior to or after this measurement period.

The study’s results underline the need for prevention programing for male Tajik MWID who have high levels of sexual risk behavior that go beyond increasing HIV knowledge to also promote evidence-based awareness of personal risk for HIV. Additionally, psychological services to counter the psychosocial effects of depression, and police-enacted stigma are needed.

Availability of data and materials

The data that support the findings of this study are openly available at https://doi.org/10.17605/OSF.IO/WS5MP [ 39 ].

Abbreviations

Human immunodeficiency virus

Migrants who inject drugs

People who inject drugs

Acquired immunodeficiency syndrome

Migrants’ Approached Self-Learning Intervention in HIV/AIDS for Tajiks

Female sex workers

Center for Epidemiologic Studies Depression scale – revised

Adjusted prevalence ratios

95% Confidence intervals

Non-governmental organizations

Eastern European and Central Asian

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Bromberg DJ, Tate MM, Alaei A, et al. “Who are You and What are You Doing Here?”: Social Capital and Barriers to Movement along the HIV Care Cascade among Tajikistani Migrants with HIV to Russia. AIDS Behav. 2021;25(10):3115–27.

Weine S, Bahromov M, Loue S, Owens L. Trauma exposure, PTSD, and HIV sexual risk behaviors among labor migrants from Tajikistan. AIDS Behav. 2012;16(6):1659–69.

Zabrocki C, Polutnik C, Jonbekov J, Shoakova F, Bahromov M, Weine S. Condom use and intimacy among Tajik male migrants and their regular female partners in Moscow. Cult Health Sex. 2015;17(1):17–33.

Mergenova G, Shaw SA, Terlikbayeva A, et al. Social Support and HIV Risks Among Migrant and Non-Migrant Market Workers in Almaty Kazakhstan. J Immigr Minor Health. 2017;19(4):809–17.

Mackesy-Amiti ME, Levy JA, Bahromov M, Jonbekov J, Luc CM. MASLIHAT Trial Data and Documentation. OSF; 2023. https://doi.org/10.17605/OSF.IO/WS5MP .

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Acknowledgements

We thank the Tajik Diaspora Union, the Volunteer Doctors Association, and Moscow HIV Prevention Center for their assistance and the study's participants and members of the MASLIHAT staff for making this research possible.

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This research was supported by a grant from the National Institute on Drug Abuse of the National Institutes of Health (USA) under Award Number R21DA050464 and by a grant from the National Center for Advancing Translational Science, NIH, through grant UL1TR002003.

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University of Illinois Chicago, Chicago, USA

Casey Morgan Luc, Judith Levy & Mary E. Mackesy-Amiti

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Mahbat Bahromov & Jonbek Jonbekov

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Contributions

J.A. Levy, M.E. Mackesy-Amiti, and M. Bahromov contributed to the study conception and design. Material preparation and data collection were performed by J. Jonbekov and C.M. Luc. Data analysis was conducted by C.M. Luc and M.E. Mackesy-Amiti. The first draft of the manuscript was written by C.M. Luc and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Casey Morgan Luc .

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This research was reviewed and approved by the Institutional Review Boards of the University of Illinois Chicago, PRISMA, and Moscow NGO “Bridge to the future” (protocol #2020–0795). The research involving human data was conducted in accordance with institutional guidelines of UIC, PRISMA, and Moscow NGO “Bridge to the future”. All participants were administered written informed consent.

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Luc, C.M., Levy, J., Bahromov, M. et al. HIV knowledge, self-perception of HIV risk, and sexual risk behaviors among male Tajik labor migrants who inject drugs in Moscow. BMC Public Health 24 , 156 (2024). https://doi.org/10.1186/s12889-023-17543-1

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DOI : https://doi.org/10.1186/s12889-023-17543-1

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Promising new approach to combat HIV

• Download PDF Copy

Researchers at Université de Montréal's affiliated hospital research center, the CRCHUM, say the discovery could help lessen and even eliminate viral loads in people undergoing antiretroviral therapy.

Metformin, a drug used to treat type 2 diabetes, could help deplete the viral reservoir and eliminate it entirely in people living with HIV who receive antiretroviral therapy, Canadian researchers say in a new study.

In 2021, a team led by immunologist Petronela Ancuta of Université de Montréal's affiliated hospital research center, the CRCHUM, showed that metformin, when taken for three months, improved patients' immunity and reduced the chronic inflammation usually associated with complications such as cardiovascular disease.

One reason these benefits are so effective is that metformin inhibits the activity of the mTOR (mechanistic target of rapamycin) molecule, which in turn slows down HIV replication in the cells of patients infected with the virus.

In the journal iScience , Ancuta and her student Augustine Fert, the study's first author and a recent Ph.D. holder, go further. They studied the molecular mechanisms of action of metformin on HIV replication in CD4 T lymphocytes, which are immune system cells that provide shelter for the virus.

In these reservoirs, HIV keeps on replicating, which contributes to the chronic inflammation by constantly activating the immune system.

The results of our in vitro tests on cells from people living with HIV and treated with antiretroviral therapy caught us off guard at first. They were a bit surprising. We discovered that metformin had both a proviral and an antiviral effect. The drug helped boost the number of HIV-infected cells, while also stopping the virus from escaping the cell." Petronela Ancuta, Immunologist, CRCHUM, Université de Montréal

Antibodies to the rescue

Another benefit of metformin is that it overexpresses the BST2 protein, which acts as a kind of glue to keep virions clinging to the surface of HIV-infected cells. The immune system then spots them and can target them with antibodies.

"Together with my colleague Andrés Finzi, we tested the ability of several broad-spectrum neutralizing anti-HIV antibodies to recognize viral reservoir cells after metformin exposure in vitro," said Ancuta. "Some of them recognized the virus very well, suggesting their ability to attract and trigger the destruction of infected cells by NK cells through a process of cellular cytotoxicity."

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These recent scientific advances mean that the "shock-and-kill" eradication strategy, often used in the fight against HIV, can be foreseen in a different way, she added.

"In people living with HIV and treated with antiretroviral therapy, we could use metformin to reactivate the reservoir cells responsible for viral replication upon treatment interruption, in combination with antibodies that are already used clinically and well tolerated. These antibodies can then detect the rare infected cells and eliminate them."

In the next phase of her research, Ancuta plans to launch a clinical trial to validate her in vitro research results, in collaboration with Finzi and their CRCHUM colleague Nicolas Chomont, and Jean-Pierre Routy of the McGill University Health Centre Research Institute.

Before she can move forward with this strategy, she will test it in preclinical models.

University of Montreal Hospital Research Centre 

Fert, A., et al. (2024). TMetformin facilitates viral reservoir reactivation and their recognition by anti-HIV-1 envelope antibodies. iScience . doi.org/10.1016/j.isci.2024.110670

Posted in: Medical Research News | Medical Condition News

Tags: AIDS , Antibodies , Antiretroviral , Cardiovascular Disease , CD4 , Cell , Chronic , Clinical Trial , Cytometry , Cytotoxicity , Diabetes , Education , HIV , HIV-1 , Hospital , Immune System , immunity , in vitro , Inflammation , Metformin , Molecule , pH , Preclinical , Protein , QC , Rapamycin , Research , students , Type 2 Diabetes , Virus

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Hiv knowledge, self-perception of hiv risk, and sexual risk behaviors among male tajik labor migrants who inject drugs in moscow, casey morgan luc.

University of Illinois at Chicago

Judith Levy

Mahbat bakhromov.

PRISMA Research Center

Jonbek Jonbekov

Mary e. mackesy-amiti.

Authors’ contributions

Associated Data

The data will be made publicly available upon completion of the study. Information on how to access the data may be obtained by contacting the corresponding author.

Background:

The interplay of HIV knowledge and self-perception of risk for HIV among people who inject drugs is complex and understudied, especially among temporary migrant workers (MWID) who inject drugs while in a host country. In Russia, Tajik migrants make up the largest proportion of Moscow’s foreign labor. Yet, HIV knowledge and self-perceived risk in association with sexual risk behavior among Tajik MWID in Moscow remains unknown.

This research examines knowledge about HIV transmission, self-perception of HIV risk, and key psychosocial factors that possibly contribute to sexual risk behaviors among male Tajik MWIDs living in Moscow.

Structured interviews were conducted with 420 male Tajik MWIDs. Modified Poisson regression models investigated possible associations between major risk factors and HIV sexual risk behavior.

Of the 420 MWIDs, 255 men (61%) reported sexual activity in the last 30 days. Level of HIV knowledge was not associated in either direction with condom use or risky sexual partnering, as measured by sex with multiple partners or female sex workers. Higher self-perceived HIV risk predicted less risky sexual partnering, but not condom use. Depression and police-enacted societal stigma were positively associated with risky sexual partnering, while loneliness and depression were associated with condomless sex.

Conclusions:

HIV prevention programing for male Tajik MWIDs must go beyond solely educating about factors associated with HIV transmission to include increased awareness of personal risk based on engaging in these behaviors. Additionally, psychological services to counter loneliness, depression, and societal stigma through police harassment are needed.

Introduction

Research has shown that labor migration from low to high human immunodeficiency virus (HIV) prevalence countries is associated with increased risk of HIV infection for migrant workers 1 , 2 This risk is further heightened among migrants who inject drugs (MWID) while in the host country. 3 In Russia, a country with high HIV prevalence, 4 HIV risk for MWID is exacerbated by disparities in the availability and provision of HIV prevention and treatment services for labor migrants. 3 , 5 – 7 In addition, MWIDs are impacted negatively by Russian policing practices that focus on enforcing petty criminal justice penalties for migrants in general and toward MWID in particular through physical harassment and syringe confiscation to discourage drug use. Such practices hinder harm reduction efforts and create barriers for MWID in accessing services for the prevention, treatment and care of HIV. 8 , 9 Meanwhile, poor working and living conditions, loneliness due to separation from family and friends at home, societal stigma, and the general emotional stress common to temporary migrant laborers in diaspora are believed to increase their vulnerability to HIV through engaging in risky sexual behavior. 5 , 6

This research present findings on HIV knowledge, perception of HIV risk, psychosocial factors, and the prevalence and correlates of HIV sexual risk behavior among male Tajik MWID who are temporarily living and working in Moscow. While in Moscow, MWID experience the “double jeopardy” of social marginalization due to their dual status as a migrant and injection drug user, both of which are thought to increase sexual risk for HIV. 3 , 10 Meanwhile, HIV knowledge and HIV risk perception have been found to influence sexual risk behavior among those who inject drugs, 11 , 12 but the interplay of these two factors on sexual risk behavior is complex and little understood. For example, while a cross-sectional study partly comprised of people who inject drugs (PWID) identified a “relatively good” level of comprehensive knowledge of HIV and acquired immunodeficiency syndrome (AIDS), the prevalence of HIV risk perception was low while sexual risk behavior was high. 13 These findings suggest that engaging in risky sexual behavior may be best explained by self-perception of being at HIV risk rather than degree of HIV knowledge alone. Yet this premise has yet to be investigated and reported in the scientific literature.

To help address this omission, this study examines the possible effects of HIV knowledge and self-perception of risk for HIV on sexual behavior among Tajik MWID while in Moscow. Also, personal and psychosocial factors appear to influence sexual risk behavior among PWID while possibly playing a role in promoting sexual risk behavior among MWID. 11 – 13 In addition, aggressive policing tactics and harassment that reflect government-enacted stigma toward migrants and MWID may form a “driving force” that increases MWID engagement in HIV sexual risk behavior. 14 Consequently, in addition to examining HIV knowledge and self-perceived risk, the analysis also investigates the possible effects of demographic and key psychosocial factors (depression, loneliness, and societal stigma toward migrants as manifested through police harassment) on sexual risk behavior. Identifying the key factors that influence sexual risk behaviors among MWID as an understudied population may help to inform prevention strategies for successfully addressing their sexual risk while adding to a better scientific understanding of the relationship between risky sexual behavior and HIV knowledge and HIV risk perception.

The research design and procedures of this study were reviewed and approved by the institutional review boards of the University of Illinois Chicago, PRISMA Research Center, and the Moscow Nongovernment Organization, “Bridge to the Future.” The analysis is based on data collected at baseline for a clinical trial assessing the efficacy of the MASLIHAT peer-education model in reducing HIV risk behavior among Tajik MWID while living in Moscow.

Recruitment:

From October 2021 to April 2022, 140 male Tajik migrant workers who inject drugs were recruited from 12 sites in Moscow: 2 Tajik diaspora organizations, 4 bazaars, and 6 construction work sites. To be eligible to participate in the research, prospective participants had to be a male Tajik migrant aged 18 or older, a current or former PWID, give written informed consent, intending to reside in Moscow for the next 12 months to permit completing baseline and four follow-up interviews, and willing to recruit two male Tajik migrants who inject drugs for interviewing as PWID network members. Network members (n=280) had to meet the same eligibility criteria as the migrant who referred them but also: 1) have injected drugs at least once in the last 30 days; and 2) be someone whom the referring migrant sees at least once a week to facilitate sharing MASLIHAT HIV prevention information. The analysis draws on data collected from the study’s sample of 420 Tajik migrant male PWID in Moscow at enrollment (baseline) prior to their random assignment to one of two research intervention conditions.

Data Collection:

After giving informed consent, participants were interviewed at the PRISMA office in Moscow or a private location of their choosing. A structured questionnaire collected information on participants’ sociodemographic characteristics, HIV-related knowledge, HIV risk perception, substance use and sexual risk behavior, experience with police-enacted societal stigma, and psychosocial measures of depression and loneliness. Participants received the customary compensation in Moscow of $20.00 for their time and transportation costs in being interviewed.

Demographic information consisted of age (years), marital status (currently married, not married/divorced), and highest educational attainment (primary school/secondary school, some university education/higher).

HIV knowledge was assessed by responses to 8 statements as being either “safe” or “unsafe” in the possibility of HIV transmission such as “being bitten by mosquitoes or other insects” and 5 statements as either “true” or “false” in terms of becoming infected such as “there is a test to determine if a person has HIV.” Responses were coded as either correct or incorrect with “don’t know” coded as incorrect. Correctly answered items were summed for a possible final score per individual between 0 – 13 (Cronbach alpha = 0.91). Low HIV knowledge was defined as scoring from 0 – 6 and moderate/high as scoring from 7–13.

Self-perception of HIV risk was assessed with two items: 1) “How likely are you to get HIV?” on a scale from “not at all likely” (0) to “very likely” (3). 2) How much do you worry about HIV?” from “not at all” (0) to a lot (2). A self-perceived HIV risk score was created per person by summing the responses to both items with scores ranging from 0 – 5. Low HIV risk perception was defined as a score of 0 or 1 and moderate/high as scoring between 2–5.

HIV sexual risk behavior was measured with three items: number of female sex partners, sex with a female sex worker, and engaging in condomless sex. To assess possible HIV risk behavior through sexual partnering, participants were asked how many women and the number of female sex workers (FSWs) with whom they had sexual intercourse in the past 30 days. Number of female sex partners was coded as: 0 or 1 sex partner = 0 (little to no risk) or ≥2 sex partners = 1 (some level of risk). Sex with FSW was coded as: 0 FSWs = 0 (no sexual intercourse reported with FSWs) or ≥1 FSWs = 1 (Sex with FSWs). To assess frequency of engaging in sex without a condom: participants were asked, “how often did you use a condom when having sexual intercourse?” for each of three partner categories: “regular female partner in Russia,” “Moscow FSW,” and “other sexual partners not engaged in selling sex.” Response categories were “never,” “sometimes,” “often,” or “always.” Responses of “always used a condom” for all three partner categories were categorized as “engaging in sex with condoms.” Otherwise, responses were categorized as engaging in condomless sex. The items were combined to create a binary measure of “any condomless sex” vs. “sex with condoms” in the past 30 days.

Psychosocial measures: Symptoms of Depression were measured using the 20-item Center for Epidemiologic Studies Depression scale - revised (CESD-R). 15 , 16 Loneliness was measured using the 20-item UCLA loneliness scale and a loneliness score was calculated as the mean of item responses (coefficient alpha: .89 - .94). 17

Societal stigma as manifested through police harassment was measured by responses ranging from “never” (0) to “very often” (4) to each of three statements: “I have been hassled by the police because I’m a migrant,” “I have been detained by the police because I’m a migrant,” and “I have been beaten by the police because I’m a migrant.” A summation score of experience with police-enacted stigma was calculated per participant ranging from 0–12.

A population-averaged Poisson regression analysis was conducted with a sandwich estimator of variance and exchangeable within-group correlation structure for network clusters to obtain adjusted prevalence ratios (aPRs) with their 95% confidence intervals (95% CI). 17 , 18 Adjusting for demographic and psychosocial factors that might impact HIV sexual risk behavior, multivariable modeling was used to examine associations between HIV knowledge and HIV risk perception and four sexual risk outcomes: sex with multiple partners (model 1), sexual activity with one or more FSWs (model 2), condomless sex (model 3) and condomless sex with FSWs (Model 4). To test the possible moderating effect of HIV risk perception on the relationship between HIV knowledge and sexual risk behavior, the analysis tested for both the separate and interactive effects of HIV knowledge and perception of HIV risk on each sexual outcome. The analyses were performed using STATA 16.1 (Stata, College Station, TX, USA) software.

Table 1 presents both the demographic characteristics of the total sample and the subsample of participants reporting sexual activity in the 30 days prior to being interviewed. The total sample was on average 30 years of age, not married/divorced, and at a secondary school education level. No significant differences were found between the demographic characteristics of men recruited through worksites, bazaars, and non-governmental organizations (NGOs) versus those whom they referred to the study as network members with the exception that the latter on average were one year younger (B = −1.07, 95% CI −1.69 – −0.46) and more likely to be on their first labor migration trip (Wald χ 2 = 7.49, p = .02).

Demographic Characteristics & HIV Sexual Risk Behavior of Male Tajik MWID

Sexual Risk Behavior.

Of the total 420 participants in the study sample, 60.7% (255) reported having been sexually active in the last 30 days prior to being interviewed. Of these, 124 men (48.6%) reported having sex with multiple partners, 177 (69.4%) reported sex with one or more FSWs, and 178 (69.8%) reported engaging in sex without a condom including 62 men (35%) who did not use one when having sex with an FSW.

HIV Knowledge.

Of the 420 participants in the study, 136 (32.4%) scored low on HIV knowledge including 88 (34.5%) of the 255 men who reported sexual activity in the last 30 days. Of the 88 sexually active men who also scored low on HIV knowledge, 45 (51.1%) reported having multiple partners, 62 (70.4%) reported sex with a FSW, and 61 (69.3%) reported engaging in condomless intercourse including 22 participants who reported not having used one with FSWs.

Self-perception of HIV Risk.

Of the 420 participants in the study, 189 (45.0%) perceived themselves to be at low risk for HIV. Of the 123 sexually active men who also perceived themselves to be at low HIV risk, 82 (66.7%) reported having multiple sex partners, 97 (78.9%) reported sexual activity with FSWs, and 83 (67.5%) reported engaging in condomless sex including 39 men who reported sexual activity with an FSW.

Multivariate analyses:

All study participants for whom there was complete data were included in the multivariable modeling of factors associated with engaging in sexual risk. Table 2 shows the adjusted prevalence ratios of each sexual risk behavior. Model 1 and 2 examine the association between key variables and engaging in sex with multiple sex partners and with FSWs. Low HIV risk perception was associated with a 79% higher prevalence of multiple sex partners (aPR: 1.79, 95% CI: 1.33, 2.40, Table 2 ) and a 28% higher prevalence of sexual activity with FSWs (aPR: 1.28, 95% CI: 1.04, 1.59) when compared to those with moderate/high HIV risk perception. Older age was associated with a lower prevalence of multiple sex partners (aPR: 0.87, 95% CI: 0.84, 0.91) and sexual activity with FSWs (0.91, 95% CI: 0.88, 0.94). A one-unit increase in depression scoring was associated with a 19% lower prevalence of multiple sex partners (aPR: 0.81, 95% CI: 0.65, 1.01). Conversely, a one-unit increase in police-enacted stigma score was associated with a 22% greater prevalence of multiple sex partners (aPR: 1.22, 95% CI: 1.01, 1.49) and a 20% greater prevalence of sexual activity with FSWs (aPR: 1.20, 95% CI: 1.03, 1.40).

Adjusted Associations with Number of Sex Partners and Condomless Sex Among Male Tajik MWID

Model 3 and Model 4 investigate condomless sex generally as well as specifically with FSWs. Neither knowledge of how HIV is transmitted, nor HIV risk perception were significantly associated with condomless sex or condomless sex with FSWs. Meanwhile, higher levels of loneliness were associated with less likelihood of engaging in condomless sex (aPR: 0.79, 95% CI: 0.68, 0.92), while a one-unit increase in depression score was associated with a 14% higher likelihood of engaging in condomless sex (aPR: 1.14, 95% CI: 1.05, 1.24) and a 26% higher likelihood of engaging in condomless sex with FSWs specifically (aPR: 1.26, 95% CI: 1.03, 1.54).

The joint effect of HIV knowledge and HIV risk perception on each sexual risk outcome is shown in Table 3 . No evidence of an additive interaction between HIV knowledge and HIV risk was found. When low HIV risk perception was present, however, the prevalence of multiple sex partners, sexual activity with FSWs, and condomless sex with FSWs was higher.

Joint Effect of HIV Knowledge and HIV Risk Perception Among Male Tajik MWID

To the best of our knowledge, this is the largest cross-sectional study to examine the factors that may influence HIV sexual risk behavior among male Tajik MWIDs as a highly understudied population. Prevalence of HIV sexual risk behavior among this migrant population is high as evidenced by the number of men engaging in sex with multiple partners (48.6%) and sex without a condom (69.8%) including with FSWs (35.0%). Of the 420 men participating in the study, 136 (32.4%) scored low on HIV knowledge and 189 (46.1%) on self-perceived HIV risk.

Prevention programs for at-risk populations typically build on the assumption that knowledge of which sexual activities carry HIV risk is needed to reduce or end high risk behavior. Yet, the study’s finding that HIV knowledge was not associated with engaging in risky sexual behavior suggests that providing Tajik migrants with HIV risk-reduction education alone likely would prove ineffective. Meanwhile, low self-perceived risk for HIV was found to be associated with greater likelihood of engaging in risky sexual activity as indicated by multiple partners and condomless sex including with FSWs. Analysis of the possible joint influence of HIV knowledge and self-perceived risk for HIV on risky sexual behavior failed to support an interaction effect. These findings suggest the role of self-perceived HIV risk over HIV knowledge as a critical factor influencing sexual risk behavior. HIV prevention programming designed to raise Tajik migrants’ and possibly other vulnerable populations’ awareness of being at personal risk is needed to strengthen the effects of HIV preventive interventions.

As for psychosocial-related factors, depression and police-enacted stigma were positively associated with sexual activity with multiple sex partners and FSWs in the last 30 days, whereas loneliness and depression were associated with condomless sex. Yet, the prevalence of all four psychosocial variables as reported in Table 1 was marginally higher among men who disclosed not having engaged in sex versus those who were sexually active during the same 30-day period. The similarity between the two sub-populations suggests that Tajik migrants in general are subject to emotional distress that can negatively affect their daily lives. Possibly among migrant males who are sexually active, these negative feelings can manifest themselves in the increased likelihood that some men will engage in less than safe sexual behavior. Whatever the reason, however, the correlation of these psychosocial with risky sex calls attention to the need for HIV prevention programming that helps to address the stress and psychosocial challenges of migrant life.

Limitations

The study’s analysis of the prevalence and correlates of risky sex focuses solely on those who reported sexual activity and excludes those men who reported being sexually inactive. It may be that some unknown number of the study’s sexually inactive participants purposely abstained from sex to avoid HIV, but the study’s data do not include inquiry into this possibility. Also, neither of the two measures used in asking participants to assess their personal risk for HIV specified that this calculation should be based solely on sexual risk. Given that the study’s sample is composed entirely of PWID, some proportion of participants may have factored in personal risk for HIV through both sex and injection drug use. While this likelihood doesn’t mitigate the validity of the study’s findings derived by examining the association between self-perceived risk for HIV and engaging in risky sexual behavior, it does not allow assessment of how much drug use alone may contribute to Tajik MWID’s self-perception of being at HIV risk.

In terms of sampling, the study’s initial participants were obtained through in-person recruitment at 10 occupational sites and by referral from 2 Tajik service networks. Each of these participants, in turn, recruited two active MWID participants through their social networks. Consequently, the results of the study may not generalize to those migrants whom these methods failed to reach or who chose not to participate. Also, our sample consists solely of men, so we cannot comment on sexual risk or its correlates among the small but growing number of Tajik women who migrate to Moscow for work. In addition, the study’s measures of sexual risk behavior focus solely on unsafe sex with female sexual partners. It is quite possible that acts of unsafe sex with another male also may have occurred during the same 30-day period. Same-sex behavior is highly stigmatized and considered morally unacceptable within the male Tajik migrant community, and it is unlikely that its occurrence would be disclosed by a participant during an initial interview. Moreover, asking a Tajik male about possibly having engaged in same-sex behavior is sufficiently affrontive culturally that it carries the potential risk of triggering the participant’s decision to end the interview. Consequently, measures of sexual risk in the study are confined solely to unsafe sex with female partners. Finally, the study’s baseline data are cross-sectional and only examined HIV risk behavior in the last 30 days. They cannot provide information about how variables of interest may have differed prior to or after this measurement period.

Conclusions

The study’s results underline the need for culturally relevant, prevention programing and other relevant interventions for male Tajik MWIDs that go beyond increasing HIV knowledge to also promote evidence-based awareness of personal risk for HIV. Additionally, psychological services to counter the psychosocial effects of loneliness, depression, and societal stigma including through police harassment are needed.

Acknowledgements

We thank the Tajik Diaspora Union, the Volunteer Doctors Association, and Moscow HIV Prevention Center for their assistance and the study’s participants and members of the MASLIHAT staff for making this research possible.

This research was supported by a grant from the National Institute on Drug Abuse of the National Institutes of Health (USA) under Award Number R21DA050464 and by a grant from the National Center for Advancing Translational Science, NIH, through grant UL1TR002003.

Abbreviations

Competing interests

The authors have no competing interests to declare that are relevant to the content of this article.

Ethics approval and consent to participate

This research was reviewed and approved by the Institutional Review Boards of the University of Illinois Chicago, PRISMA, and Moscow NGO “Bridge to the future” (protocol #2020-0795). The research involving human data was conducted in accordance with institutional guidelines of UIC, PRISMA, and Moscow NGO “Bridge to the future”. All participants were administered written informed consent.

Consent for publication

Not applicable

Code availability

Contributor Information

Casey Morgan Luc, University of Illinois at Chicago.

Judith Levy, University of Illinois at Chicago.

Mahbat Bakhromov, PRISMA Research Center.

Jonbek Jonbekov, PRISMA Research Center.

Mary E. Mackesy-Amiti, University of Illinois at Chicago.

Availability of data and materials

The Moscow Theater Hostage Crisis: Incapacitants and Chemical Warfare

November 4, 2002 By Chemical and Biological Weapons Nonproliferation Program(1)

On October 23, 2002, in the middle of an evening performance at a Moscow music theater, some 50 Chechen terrorists equipped with firearms as well as large quantities of explosives suddenly seized the venue and the 800 people inside. The terrorists threatened to kill everyone inside unless Russia ended the war in Chechnya. Although the Chechen militants agreed to release some of the hostages during the first couple of days, negotiations with the Russian authorities eventually stalled. Just before dawn on October 26, Russian special police units resorted to using an incapacitating gas based on the drug fentanyl to end the crisis. All of the Chechen militants were killed, and most of the civilian captives survived. But while the operation was largely a success, at least 117 of the hostages died from the effects of the gas. (2) That so many died because of poisoning has been the source of some controversy about how the entire operation was handled. But even while acknowledging that mistakes may have been made by the police, most Russians seem to support the action taken by Moscow authorities.

Following the resolution of the hostage crisis, much has also been made of the Moscow theater incident with respect to the Chemical Weapons Convention (CWC) and even the Biological Weapons Convention (BWC). The concern is two-fold: first, did this action violate international law, and second, does possession of the agent used in this instance suggest that the Russians have been covertly pursuing chemical weapons in a manner which could be considered in breach of the CWC?

Vladamir Putin Visits Theater Victims, Source: WikiMedia Commons

Background on Opiates and Chemical Warfare

“An incapacitating agent is an agent producing physiological or mental effects that may persist for hours or days after exposure to the agent has ceased.” US Army field manual FM 3-9  (3)

Especially during the Cold War, a great deal of research was expended by the United States and the former Soviet Union on chemical substances that would not necessarily kill, but would instead merely incapacitate enemy personnel. During the heyday of the US chemical warfare (CW) program (1950s-1960s), a wide number of pharmacological substances were investigated for their potential as incapacitants, including depressants, hallucinogens (e.g., LSD), belladonna drugs (scopolamine, BZ), and the opiate derivatives. The latter category refers to those drugs like morphine that fit receptors in the human brain/nervous system, as a key would fit a lock, releasing pain-killing endorphins and inducing a state of euphoria. Given the right amount, opium-based drugs can also induce sleep/unconsciousness.

Such properties of poppy-derived medicaments had been known for many centuries, and morphine had already found some use as a total anesthetic agent by the late 1800s. However, the use of morphine as a total anesthetic sometimes led to deadly complications both during and following medical procedures. In 1939, the synthesis of meperidine and its improved safety profile led to renewed interest in the use of opiates for anesthesia. (4)

But arguably the most important development in opiate drugs in medicine was the synthesis of fentanyl, its structure first patented by Janssen in France (1963). Fentanyl remains among the more often used compound in combination with other drugs, or even by itself for anesthesia. However, large doses of fentanyl have also been known to increase risks for complications, particularly in terms of respiratory depression during recovery. Recently, a number of different analogues based on fentanyl have been introduced, including sufentanil, alfentanil, and remifentanil (cr. 1996) for use in anesthesia.

If drugs like the belladonna alkaloids (atropine, BZ, etc.) could be utilized in chemical weapons, some CW specialists have wondered if opioid derivatives could also play a role in warfare or in certain tactical operations. During their own military-related chemical research, however, US military chemists found that the dose of opiate-related drugs needed to cause the desired degree of incapacitation was not far from the lethal dose. In the case of the opiates, for example, it the difference between incapacitating and lethal quantities was found to be about 10-20 fold. With such a narrow margin of relative safety, there was not much rationale to include these substances as incapacitating weapons. (5) (The United States eventually weaponized BZ as its standardized incapacitant, but due to the unpredictable effects of this agent in humans, these stocks were destroyed during the 1980s.)

Clinical Data for Fentanyl-Based Compounds

Comparing the effective dose (ED50), and the lethal dose (LD50) for 50% of a given population

Lowest effective dose: ED50 mg/kg Lethal dose: D50, mg/kg

Meperidine 6.0 – Lowest Effective Dose 29.0 – Lethal Dose 4.8 – Relative Safety Index

Alfentanil 0.044 – Lowest Effective Dose 47.5  – Lethal Dose 1,080 – Relative Safety Index

Fentanyl 0.011 – Lowest Effective Dose 3.1 – Lethal Dose 277 – Relative Safety Index

Sufentanil 0.007 – Lowest Effective Dose 17.9 – Lethal Dose 25,211 – Relative Safety Index

Lofentanil 0.0059 – Lowest Effective Dose 0.066 – Lethal Dose 112 – Relative Safety Index

Carfentanil 0.0034 – Lowest Effective Dose 3.4 – Lethal Dose 10,000 – Relative Safety Index

Fentanyl and Its Suggested Role in Vietnam

Although considered unfit for large scale production or weaponization, opiate-drugs like fentanyl may have had some applications in specialized warfare or covert operations. During his tenure in Southeast Asia (1966-1968), retired Major General John K. Singlaub recalls a time when the military use of fentanyl or similar drugs was considered for tactical roles in Vietnam. The US Military Advisory Command (MAC) Studies and Observation Group (SOG) was tasked to do, among other things, intelligence gathering missions by capturing enemy officers for interrogation. This proved to be among the most daunting challenges that Singlaub and others faced along the Ho Chi Minh trail, where North Vietnam shuttled logistical and other support to the Viet Cong irregulars in the South. While most of the Vietnamese carrying supplies on foot or on bicycles were low-ranked soldiers – mainly peasants pressed into labor – some high-ranking NVA officers would also be present. Often, when SOG units engaged these caravans it would quickly turn into a desperate firefight, resulting in the death of the NVA officers, as well as many of those who were merely carrying supplies for the Viet Cong guerrillas. General Singlaub wondered if there was a way to temporarily knock out the isolated individuals, while scattering away the irrelevant logistical support units. They could then bring these NVA officers in for questioning. One of the plans was to utilize something along the lines of a tranquilizing dart with fentanyl or related substance. In the end, however, the science advisor to General Westmoreland did not approve of this venture, and only CS (a riot control agent) was ever approved for the Southeast theater of operations. (6)

Israeli Mossad, 1997

In October 1997, the Israeli Mossad used fentanyl in either an assassination attempt or a snatch-and-grab operation that subsequently went awry. In this case, Israeli intelligence operatives (including one physician) traveled to Jordan. There, they followed Khalid Mishal, a Jordanian-based Hamas leader in a car. The plan was to deliver fentanyl in a spray that would be absorbed through the target’s ear, but Khalid Mishal was able to escape. Following the event, he was reportedly affected by the drug, requiring significant medical attention afterwards. (7)

What Chemical Was Used in the Moscow Theater Raid?

One might consider remifentanil, a related analogue to fentanyl, to be a possible candidate for the Russian version of the incapacitating agent used in the Moscow theater. Among other opiate analogues, remifentanil is rather unique and extremely potent, with relatively fast action but also short duration. Its chemical structure also allows the body to quickly metabolize the substance into non-toxic and water soluble forms. (8) It is therefore possible that this or a similar compound was chosen because of lower associated risks for both the hostage-takers and hostages. And, as is the case with other compounds, an effective antidote to opiates is widely available in the form of naloxone (Narcan). While Russian authorities insist that emergency personnel were prepared with 1,000 antidotes in anticipation of the raid, controversy continues over whether local hospitals and physicians were adequately informed about the gas used during the operation. (9)

Did Its Use by Police Contravene International Law?

Even allowing for the fact that Moscow authorities were faced with a desperate situation, some have argued that the Russian operation was conducted with inadequate attention to the safety of innocent civilians. But whether or not the use of an incapacitating gas contravened the CWC is much more difficult to discern. In general, the CWC’s wording allows for the use of chemical agents for “law enforcement” purposes, as stated in Article II 9(d) (“Purposes Not Prohibited Under this Convention”). The chemicals to be used in this context, although not precisely identified, are essentially taken to represent riot control agents. A riot control agent (RCA) is defined in Article II, pt. 7 as “any chemical not listed in a Schedule, which can produce rapidly in humans sensory irritation or disabling physical effects which disappear within a short time frame following termination of exposure.” This is in stark contrast to those CW agents that are explicitly named in the CWC’s three Schedules, such as VX or mustard gas. (Simply stated, the CWC Schedules are compilations of chemicals that have been used in chemical weapons or their production, and are therefore of particular concern to the Convention.)

Determining where fentanyl-derivatives fall in this spectrum of lethal vs. non-lethal agents is, therefore, of utmost importance when evaluating whether the incident in question was in fact a violation of the CWC. In the final analysis, because it is not listed in any of the Schedules and is traditionally characterized by the rapid onset and short duration (15 to 30 minutes) of analgesia, fentanyl can be legally considered a riot control agent according to the definition set forth in the CWC. However, additional and binding terms in the CWC do apply. While Article VI, “Activities Not Prohibited Under this Convention,” explicitly notes that a listed toxic chemical is subject to the restrictions inherent to its Schedule, such as import/export controls and production limitations, riot control agents have no similar restrictions. But the overall requirement of the Convention that each State Party declare any possession of Scheduled agents does have a parallel rule with respect to RCAs. In accordance with the terms of Article III 1(e), within 30 days of the Convention entering into force each State Party was to have specified “the chemical name, structural formula and Chemical Abstracts Service (CAS) registry number, if assigned, of each chemical it holds for riot control purposes. This declaration shall be updated not later than 30 days after any change becomes effective.”

What does this mean? If it is conceded that fentanyl was utilized as a riot control agent for law enforcement purposes. A final legal hurdle still remains, namely, that fentanyl and its delivery systems should have been declared by Russia under the terms of the Convention. As far as open sources are concerned, the analysis effectively ends here; however, because Article III declarations are generally not available in the public domain, and whether such a declaration was made by the Russians for fentanyl-like compounds – or any other chemical agent – cannot be determined here. This last point does leave at least some question as to whether the Russians were in fact in strict compliance with the CWC.

In this case, however, not only is it apparent that the use of the opiate gas was legitimate given the circumstances, the decision to do so appears in the end to have been morally justified from the perspective of the Russians. Ultimately, as this issue is debated over the coming weeks the overall intent in possessing this form of RCA and delivery system may prove to be the key: This fentanyl-like drug was not intended to serve as either a lethal or incapacitating agent on a battlefield. Russian officials believed it to be the most humane solution to a volatile hostage situation.

The terrorist group that seized the hostages at the Moscow Dubrovka Theatre Center was a particularly extreme and violent group. Its leader, Movsar Barayev, was the son of a murdered Chechen guerrilla leader named Abdi Barayev, whose own fighters were notorious for their brutal and bloodthirsty behavior (as was reflected in their murder and beheading of three Britons and one New Zealander in 1998). Movsar Barayev’s hostage takers vehemently rejected Russian offers of safe passage in exchange for releasing the hostages, and repeatedly boasted of their willingness to “punish the sinners” if the Russians attacked the theater or failed to begin withdrawing from Chechnya. The latter was clearly an impossible demand that the Russian government would never meet, and all the while the terrorists were making it clear that they were on a “martyrdom” mission and were willing to kill both the hostages and themselves. In such a context, the Russians were facing a “no-win” situation and were therefore probably right to act when and as they did. Knowing the extreme nature of Barayev and his followers – as well as other fanatical Islamist groups that share similar goals and tactics, both in Chechnya and elsewhere – it is difficult to envision any response that could have ended this takeover without resulting in significant numbers of casualties.

(1) The Chemical and Biological Weapons Nonproliferation Program (CBWNP) would like to thank Mark Gorwitz of the Defense Technical Information Center (DTIC) for his generous assistance with open source data and his very helpful advice. (2) Susan B. Glasser and Peter Baker, “Russia Confirms West’s Suspicions about Deadly Gas,” Washington Post , October 31, 2002, p. 15. (3) Quoted in James A.F. Compton, Military Chemical and Biological Agents (Caldwell, NJ: The Telford Press, 1987), p. 254. (4) Peter L. Bailey, Talmage D. Egan, and Theodore H. Stanely, “Intravenous Opioid Anesthetics,” in Ronald D. Miller, ed., Anesthesia , 5th edition (Philadelphia: Churchill Livingstone, 2000), p. 274. (5) James S. Ketchum and Frederick R. Sidell, “Incapacitating Agents,” in Frederick R. Sidell, Ernest T. Takafuji, and David R. Franz, eds., Medical Aspects of Chemical and Biological Warfare (Washington, DC: Borden Institute, 1997), p. 293. (6) Interview with General Singlaub, August 13, 1998. (7) “Physician Member of Hit Team, Paper Says,” Canadian Medical Association Journal , Vol. 157, No. 11, December 1997, p. 1504; Lisa Beyer, “Don’t Try This at Home – Or in Aman,” Time , Vol. 150, No. 17, October 27, 1997, p. 27. (8) Donald R. Stanski, “Monitoring Depth of Anesthesia,” in Ronald D. Miller, ed., Anesthesia , 5th edition (Philadelphia: Churchill Livingstone, 2000), pp. 1103-4. (9) Susan B. Glasser and Peter Baker, “Russia Confirms West’s Suspicions about Deadly Gas,” Washington Post , October 31, 2002, p. 15.

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