Neuroinflammatory and Syndemic Pathways in HIV Prep Adherence: A Systematic Review

Background: Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, yet adherence remains suboptimal. Alcohol misuse, post-traumatic stress disorder (PTSD), and gastrointestinal (GI) dysbiosis have been proposed as overlapping barriers. This systematic review aimed to evaluate how these factors independently and interactively affect PrEP adherence among HIV-negative populations in the United States.
Methodology: A systematic search was conducted in PubMed, PsycINFO, Scopus, and Web of Science for studies published between 2016 and March 2025 on PrEP adherence, alcohol use, PTSD, and the gut microbiome. Eligible studies included peer-reviewed human research in English that examined PrEP adherence in relation to at least one of these factors, while non-human and non-US studies were excluded. Two reviewers independently screened and extracted data, with disagreements resolved by consensus. Data were analyzed descriptively in R version 4.3.1, and findings were synthesized narratively due to heterogeneity across studies.
Results: Fifteen studies met the inclusion criteria. Hazardous alcohol use was associated with a 55–60% increase in GI complaints, and adherence rates reduced to 54–60%, versus >80% in non-drinkers. PTSD prevalence among PrEP users ranged from 28–43%, with severity 40–50% higher among alcohol users; trauma-related avoidance and cognitive impairment were key drivers of missed doses. Microbiome analyses suggested reduced Lactobacillus/Bifidobacterium and elevated Enterobacteriaceae were associated with reported intolerance and discontinuation. Structural inequities, stigma, and racial disparities further compounded nonadherence, particularly among Black and Latinx MSM.
Conclusions: Alcohol misuse, PTSD, and GI dysbiosis appear to interact as a syndemic that may undermine PrEP adherence. Addressing these barriers requires integrated, trauma-informed, and microbiome-sensitive interventions to improve HIV prevention outcomes.

HIV prevention, PrEP adherence, alcohol use

1. Antonini M, Silva IEd, Elias HC, Gerin L, Oliveira AC, Reis RK. Barriers to Pre-Exposure Prophylaxis (PrEP) use for HIV: an integrative review. Rev Bras Enferm 2023;76(3):e20210963. [Google Scholar] [Crossref]

2. Février M, Dorgham K, Rebollo A. CD4 T cell depletion in human immunodeficiency virus (HIV) infection: role of apoptosis. Viruses 2011;3(5):586. [Google Scholar] [Crossref]

3. Blumenthal J, Haubrich R. Pre-exposure prophylaxis for HIV infection: how antiretroviral pharmacology helps to monitor and improve adherence. Expert Opin Pharmacother 2013;14(13):1777–1785. [Google Scholar] [Crossref]

4. Moyo E, Moyo P, Murewanhema G, Mhango M, Chitungo I, Dzinamarira T. Key populations and Sub-Saharan Africa's HIV response. Frontiers in public health 2023;11:1079990. [Google Scholar] [Crossref]

5. Blumenthal J, Haubrich R. Pre-exposure prophylaxis for HIV infection: how antiretroviral pharmacology helps to monitor and improve adherence. Expert Opin Pharmacother 2013;14(13):1777–1785. [Google Scholar] [Crossref]

6. Hasan MR, Davidson R. Understanding Barriers to PrEP Adherence: A Brief Report on the Combined Effects of Alcohol Misuse, PTSD, and Gut Microbiome Disruption in HIV Prevention. Asian Journal of Public Health and Nursing 2025;2(2):14–27. [Google Scholar] [Crossref]

7. Spinner CD, Boesecke C, Zink A, Jessen H, Stellbrink H, Rockstroh JK, et al. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans. Infection 2016;44:151–158. [Google Scholar] [Crossref]

8. Tetteh RA, Yankey BA, Nartey ET, Lartey M, Leufkens HG, Dodoo AN. Pre-exposure prophylaxis for HIV prevention: safety concerns. Drug safety 2017;40:273–283. [Google Scholar] [Crossref]

9. Hasan MR, Yusuf MA. Microbial Dysbiosis in Diabetic Children with Enteric Hepatitis: The Global Phenomenon and Bangladesh's Contextual Significance. Bangladesh Journal of Infectious Diseases 2023;10(2):56–58. [Google Scholar] [Crossref]

10. Ray S, Sil S, Kannan M, Periyasamy P, Buch S. Role of the gut-brain axis in HIV and drug abuse-mediated neuroinflammation. Advances in Drug and Alcohol Research 2023;3:11092. [Google Scholar] [Crossref]

11. Rousseau RK, Walmsley SL, Lee T, Rosenes R, Reinhard RJ, Malazogu F, et al. Randomized, blinded, placebo-controlled trial of de Simone formulation probiotic during HIV-associated suboptimal CD4 T cell recovery. JAIDS J Acquired Immune Defic Syndromes 2022;89(2):199–207. [Google Scholar] [Crossref]

12. Hasan MR. Understanding Diabetes Care Barriers Through Community Voices: A Brief Qualitative Report from Jefferson County, Kentucky. Asian Journal of Public Health and Nursing 2025;2(2):1–7. [Google Scholar] [Crossref]

13. Rosas Cancio-Suárez M, Díaz-Álvarez J, Ron R, Martínez-Sanz J, Serrano-Villar S, Moreno S, et al. From innovation to implementation: the evolution of HIV pre-exposure prophylaxis and future implications. Pathogens 2023;12(7):924. [Google Scholar] [Crossref]

14. Tsuyuki K, Pitpitan EV, Levi-Minzi MA, Urada LA, Kurtz SP, Stockman JK, et al. Substance use disorders, violence, mental health, and HIV: differentiating a syndemic factor by gender and sexuality. AIDS and Behavior 2017;21(8):2270–2282. [Google Scholar] [Crossref]

15. Dillon SM, Frank DN, Wilson CC. The gut microbiome and HIV-1 pathogenesis: a two-way street. AIDS 2016;30(18):2737–2751. [Google Scholar] [Crossref]

16. Bishehsari F, Magno E, Swanson G, Desai V, Voigt RM, Forsyth CB, et al. Alcohol and gut-derived inflammation. Alcohol research: current reviews 2017;38(2):163. [Google Scholar] [Crossref]

17. Hasan MR, Rogers WT, Yusuf MA, Muna MA, Kanij FR, Sajid H. A comprehensive review on antimicrobial resistance in uropathogens isolated from ICU patients in the south-east Asian region. International Journal of Science and Research Archive, 2025, 14(02), 527-542.Article DOI: https://doi.org/10.30574/ijsra.2025.14.2.0340. [Google Scholar] [Crossref]

18. Stiksrud B, Nowak P, Nwosu FC, Kvale D, Thalme A, Sonnerborg A, et al. Reduced levels of D-dimer and changes in gut microbiota composition after probiotic intervention in HIV-infected individuals on stable ART. JAIDS J Acquired Immune Defic Syndromes 2015;70(4):329–337. [Google Scholar] [Crossref]

19. Hasan MR, Yusuf MA, Rogers W, Muna MA. Exploring Dengue Transmission Trends, Public Health Challenges, and Intervention Efficacy Among Adolescents in Dhaka City: An Observational Study. Asian Journal of Public Health and Nursing 2025;2(1). [Google Scholar] [Crossref]

20. Smith ND, Cottler LB. The epidemiology of post-traumatic stress disorder and alcohol use disorder. Alcohol research: current reviews 2018;39(2):113. [Google Scholar] [Crossref]

21. Spencer LY, Cuca YP, Davis K, Ayafor V, Lewis-Chery S, Chen CA, et al. Differences in HIV outcomes and quality of life between older and younger Black women with HIV in the United States, 2021–2023. Am J Public Health 2025;115(S1):S57–S67. [Google Scholar] [Crossref]

22. Willie TC, Overstreet NM, Sullivan TP, Sikkema KJ, Hansen NB. Barriers to HIV medication adherence: examining distinct anxiety and depression symptoms among women living with HIV who experienced childhood sexual abuse. Behavioral Medicine 2016;42(2):120–127. [Google Scholar] [Crossref]

23. Pearson CR, Kaysen D, Belcourt A, Stappenbeck CA, Zhou C, Smartlowit-Briggs ML, et al. Post-traumatic stress disorder and HIV risk behaviors among rural American Indian/Alaska Native women. Am Indian Alsk Native Ment Health Res 2015;22(3):1. [Google Scholar] [Crossref]

24. Meyer J, Price C, Tracey D, Sharpless L, Song Y, Madden L, et al. Preference for and efficacy of a PrEP decision aid for women with substance use disorders. Patient preference and adherence 2021:1913–1927. [Google Scholar] [Crossref]

25. Zhai Y, Isadore KM, Parker L, Sandberg J. Responding to the HIV health literacy needs of clients in substance use treatment: The role of universal PrEP education in HIV health and prevention. International Journal of Environmental Research and Public Health 2023;20(19):6893. [Google Scholar] [Crossref]

26. Hasan MR. Exploring the Relationship Between Opioid Use Disorder and Major Depressive Disorder: A Case Study from Kentucky of United States. Journal of Current and Advance Medical Research 2024;11(1):50–55. [Google Scholar] [Crossref]

27. Spencer LY, Cuca YP, Davis K, Ayafor V, Lewis-Chery S, Chen CA, et al. Differences in HIV outcomes and quality of life between older and younger Black women with HIV in the United States, 2021–2023. Am J Public Health 2025;115(S1):S57–S67. [Google Scholar] [Crossref]

28. Hasan MR, Haq ZU, Muna MA. The Hidden Continuum of Risk: Behavioral and Mental Health Pathways from Tobacco Consumption to Illicit Drug Use Among University Students in Bangladesh. 2025. [Google Scholar] [Crossref]

29. Zeeshan UH, Hasan MR. Exploring the association between psychological distress and cannabis edible use among US adults: a descriptive epidemiologic study. International Journal of Pharma and Biosciences 2025:6–16. [Google Scholar] [Crossref]

30. Peprah E, Myers B, Kengne A, Peer N, El-Shahawy O, Ojo T, et al. Using a syndemics framework to understand how substance use contributes to morbidity and mortality among people living with HIV in Africa: a call to action. International journal of environmental research and public health 2022;19(3):1097. [Google Scholar] [Crossref]

31. New-Aaron MO. Hepatocyte-Hepatic Stellate Cell Axis in Potentiation of Alcohol and HIV-Induced Liver Injury. 2022. [Google Scholar] [Crossref]

32. Kabir R, Bai ACM, Syed HZ, Hasan MR, Vinnakota D, Kar SK, et al. The effect of COVID-19 on the mental health of the people in the Indian subcontinent: a scoping review. Nepal Journal of Epidemiology 2023;13(2):1268. [Google Scholar] [Crossref]

33. Farley JE, Beuchamp G, Bergman AJ, Hughes JP, Batey DS, Del Rio C, et al. The impact of stigma and sexual identity on PrEP awareness and use among at-risk men who have sex with men in four US cities (HPTN 078). Stigma and health 2024;9(3):400. [Google Scholar] [Crossref]

34. Kabir R, Vinnakota D, Dehghani L, Sathian B, Padhi BK, Hasan MR. HIV and Violence among Female Sex Workers in India: A Scoping. Women's Health Problems: A Global Perspective 2024;3. [Google Scholar] [Crossref]

35. Moschese D, Lazzarin S, Colombo ML, Caruso F, Giacomelli A, Antinori S, et al. Breakthrough acute HIV Infections among pre-exposure prophylaxis users with high adherence: a narrative review. Viruses 2024;16(6):951. [Google Scholar] [Crossref]

36. Smith ND, Cottler LB. The epidemiology of post-traumatic stress disorder and alcohol use disorder. Alcohol research: current reviews 2018;39(2):113. [Google Scholar] [Crossref]

37. Satre DD, Metz VE, Van Doren N, Silverberg MJ, Lam JO. Alcohol Use and Its Associations With Frailty, Fractures, and Falls Among Older Adults With HIV. Alcohol Research: Current Reviews 2025;45(1):08. [Google Scholar] [Crossref]

38. Braz Junior RP, Cesar GA, Amianti C, Bandeira LM, Da Silva A, Motta-Castro A. Behind prep decisions: understanding user patterns and discontinuation factors in real-world. AIDS and Behavior 2024;28(9):2979–2989. [Google Scholar] [Crossref]

39. Obeagu EI, Alsadi RA. MIND AND IMMUNITY: EXPLORING THE INTERPLAY BETWEEN HIV AND MENTAL HEALTH DISORDERS-A REVIEW. Universal Journal of Pharmaceutical Research 2025. [Google Scholar] [Crossref]

40. Bragazzi NL, Khamisy-Farah R, Tsigalou C, Mahroum N. HIV pre-exposure prophylaxis and its impact on the gut microbiome in men having sex with men. Frontiers in Microbiology 2022;13:922887. [Google Scholar] [Crossref]

41. Bromberg DJ, Mayer KH, Altice FL. Identifying and managing infectious disease syndemics in patients with HIV. Current Opinion in HIV and AIDS 2020;15(4):232–242. [Google Scholar] [Crossref]

42. Hasan MR, Muna MA, Rahman S. Impact of Hazardous Alcohol Use on Pre-Exposure Prophylaxis Adherence: A Meta-Analysis of Biological and Psychological Pathways. Journal of Clinical Practice and Medical Research 2025;1(3):67–76. [Google Scholar] [Crossref]

43. Hasan MR, Mclessey L, Haque A, Muna MA, Haq ZU. A multilevel perspective on PrEP adherence in HIV prevention: an integrative review guided by the socioecological model. British Journal of Nursing Studies 2025;5(3):23–43. [Google Scholar] [Crossref]

44. Cheu RK, Gustin AT, Lee C, Schifanella L, Miller CJ, Ha A, et al. Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism. PLoS pathogens 2020;16(12):e1009024. [Google Scholar] [Crossref]

45. Arnold T, Brinkley-Rubinstein L, Chan PA, Perez-Brumer A, Bologna ES, Beauchamps L, et al. Social, structural, behavioral and clinical factors influencing retention in Pre-Exposure Prophylaxis (PrEP) care in Mississippi. PloS one 2017;12(2):e0172354. [Google Scholar] [Crossref]

46. Hasan MR. Mental Health Challenges in Bangladesh Based on the Integrated Assessment of Illicit Drug Use, Substance Abuse, Tobacco Consumption, and Escalating Suicidal Tendencies: A Comprehensive Review. Bangladesh Journal of Infectious Diseases 2024;11(1). [Google Scholar] [Crossref]

47. Littlefield KM, Schneider JM, Neff CP, Soesanto V, Siebert JC, Nusbacher NM, et al. Elevated inflammatory fecal immune factors in men who have sex with men with HIV associate with microbiome composition and gut barrier function. Frontiers in Immunology 2022;13:1072720. [Google Scholar] [Crossref]

48. Yan J, Ouyang J, Isnard S, Zhou X, Harypursat V, Routy J, et al. Alcohol use and abuse conspires with HIV infection to aggravate intestinal dysbiosis and increase microbial translocation in people living with HIV: a review. Frontiers in Immunology 2021;12:741658. [Google Scholar] [Crossref]

49. Gan J, Nazarian S, Teare J, Darzi A, Ashrafian H, Thompson AJ. A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose: mannitol ratio in coeliac and Crohn’s disease. BMC gastroenterology 2022;22(1):16. [Google Scholar] [Crossref]

50. Hasan, M. R., Halim, F. B., Haque, A., Haq, Z. U., & Muna, M. A. (2025). A Quantitative Analysis of Lifestyle Behaviors and Psychosocial Determinants of Adult Obesity in the United States. ICRRD Quality Index Research Journal, 7(1), 101-126. [Google Scholar] [Crossref]

51. Vuković M, Nosek I, Medić Stojanoska M, Kozić D. Neurometabolic and Neuroinflammatory Consequences of Obesity: Insights into Brain Vulnerability and Imaging-Based Biomarkers. International Journal of Molecular Sciences 2026;27(2):958. [Google Scholar] [Crossref]

52. Hasan MR, Parker FW. Barriers and Behavioral Determinants of Diabetes Care Access: A Theory of Planned Behavior Assessment in a Southern US Urban Community. ADCES in Practice :2633559X251385644. [Google Scholar] [Crossref]

53. Haldane V, Legido-Quigley H, Chuah FLH, Sigfrid L, Murphy G, Ong SE, et al. Integrating cardiovascular diseases, hypertension, and diabetes with HIV services: a systematic review. AIDS Care 2018;30(1):103–115. [Google Scholar] [Crossref]

54. Hasan MR, Yusuf MA, Rogers WT, Egbury G, Muna MA. Global Patterns and Emerging Challenges of Human Monkeypox Virus: An In-Depth Narrative Review and Analysis. Bangladesh Journal of Medical Microbiology 2024;18(2):120–130. [Google Scholar] [Crossref]

55. Liu BM, Rakhmanina NY, Yang Z, Bukrinsky MI. Mpox (Monkeypox) virus and its co-infection with HIV, sexually transmitted infections, or bacterial superinfections: double whammy or a new prime culprit? Viruses 2024;16(5):784. [Google Scholar] [Crossref]

56. Hasan MR. Assessing the Psychosocial Determinants of Mental Health Decline Among Bangladeshi University Students During the COVID-19 Pandemic: A Rapid Systematic Review. Asian Journal of Public Health and Nursing 2024;1(3). [Google Scholar] [Crossref]

57. Edeza A, Karina Santamaria E, Valente PK, Gomez A, Ogunbajo A, Biello K. Experienced barriers to adherence to pre-exposure prophylaxis for HIV prevention among MSM: a systematic review and meta-ethnography of qualitative studies. AIDS Care 2021;33(6):697–705. [Google Scholar] [Crossref]

58. Presti R M, Yeh E, Williams B, Landay A, Jacobson J M, Wilson C, et al, editors. A randomized, placebo-controlled trial assessing the effect of VISBIOME ES probiotic in people with HIV on antiretroviral therapyOpen Forum Infectious Diseases; Oxford University Press US; 2021. [Google Scholar] [Crossref]

59. Farley JE, Beuchamp G, Bergman AJ, Hughes JP, Batey DS, Del Rio C, et al. The impact of stigma and sexual identity on PrEP awareness and use among at-risk men who have sex with men in four US cities (HPTN 078). Stigma and health 2024;9(3):400. [Google Scholar] [Crossref]

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