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BackgroundCannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined.MethodsThe impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry.ResultsHeavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells.ConclusionsWhile the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

Commensal organisms appear to play significant roles in normal homeostasis as well as in the pathogenesis of HIV infection in a number of different organ systems. On November 17th and 18th, 2016, leading researchers from around the world met to discuss their insights on advances in our understanding of HIV and the microbiome at the National Institutes of Health (NIH) in Bethesda. Dr. Elhanan Borenstein of the University of Washington gave a keynote address where he discussed new developments in systems biology which hold the promise of illuminating the pathways by which these organisms interact with human physiology. He suggested that we need to get past correlations in microbiome research by using models and informatics which incorporate metagenomics to predict functional changes in the microbiome.

Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status. Cannabis use was assessed by self-administered Cannabis Use Disorder Identification Test (CUDIT) questionnaires and rectal microbial community alpha-diversity metrics were assessed via 16S ribosomal ribonucleic acid (rRNA) sequencing in a subset of YSGM (n = 42) in the RADAR cohort (aged 16–29) in Chicago. Multivariable regression models were used to assess the relationship between cannabis use and microbiome alpha-diversity metrics, adjusting for HIV status and other risk characteristics, including inflammation, which was evaluated by plasma levels of C-reactive protein (CRP). Problematic cannabis use, but not general use, was significantly inversely associated with microbial community richness (Adj. Beta = −8.13; 95% confidence interval [CI]: −15.68 to −0.59) and Shannon diversity (Adj. Beta = −0.04; 95% CI: −0.07 to 0.009). No significant association was observed between CUDIT score and community evenness, nor was any significant moderation observed by HIV status. We observed that problematic cannabis use was associated with reduced microbial community richness and Shannon diversity, adjusting for within population differences in inflammation and HIV status. Future research should aim to assess how cannabis use contributes to microbiome-related health factors among YSGM and if decreasing cannabis use can restore gut microbial community structure. [ABSTRACT FROM AUTHOR]

Background: Although nonoptimal vaginal bacteria and inflammation have been associated with increased HIV risk, the upstream drivers of these phenotypes are poorly defined in young African women. Setting: Mombasa, Kenya. Methods: We characterized vaginal microbiome and cytokine profiles of sexually active young women aged 14-24 years (n = 168) in 3 study groups: those engaging in formal sex work, in transactional sex, and nonsex workers. Vaginal secretions were collected using self-inserted SoftCup, and assayed for cytokines and vaginal microbiome through multiplex ELISA and 16S rRNA sequencing, respectively. Epidemiological data were captured using a validated questionnaire. Results: The median age of participants was 20 years (interquartile range: 18-22 years). Approximately two-thirds of young women (105/168) had vaginal microbial communities characterized by Gardnerella and/or Prevotella spp. dominance; a further 29% (49/168) were predominantly Lactobacillus iners. Microbiome clustering explained a large proportion of cytokine variation (>50% by the first 2 principal components). Age was not associated with vaginal microbial profiles in bivariable or multivariable analyses. Women self-identifying as sex workers had increased alpha (intraindividual) diversity, independent of age, recent sexual activity, HIV, and other sexually transmitted infections (beta = 0.47, 95% confidence interval: 0.05 to 0.90, P = 0.03). Recent sex (number of partners or sex acts last week, time since last vaginal sex) correlated with increased alpha diversity, particularly in participants who were not involved in sex work. Conclusion: Nonoptimal vaginal microbiomes were common in young Kenyan women and associated with sex work and recent sexual activity, but independent of age. Restoring optimal vaginal microflora may represent a useful HIV prevention strategy. [ABSTRACT FROM AUTHOR]

Women and girls represent a key population driving new HIV infections and persistence of the HIV pandemic. A key determinant of HIV susceptibility is the composition of the vaginal microbiome, which can influence the local immune cell population, inflammation status, and HIV prevention drug levels. While a low-diversity composition dominated by Lactobacillus crispatus is associated with a decreased risk of HIV acquisition, high diversity environments associated with bacterial vaginosis increase risk of HIV. Given the important role of the vaginal microbiome in determining HIV susceptibility, altering the microbiome towards a Lactobacillus -dominated state is an attractive complementary strategy to reduce HIV incidence rates. Here, we provide an overview of the mechanisms by which the vaginal microbiome may contribute to HIV acquisition risk. Furthermore, we address the advantages and limitations of historical treatments and emerging technologies under investigation to modify the vaginal microbiome, including: antibiotics, bacteriophages, probiotics, topicals, and engineered bacteria. By addressing the current state of vaginal microbiome knowledge and strategies for manipulation, we hope to amplify the growing calls for increased resources and research into vaginal microbial health, which will be essential to accelerating preventative efforts amongst the world's most vulnerable populations. [ABSTRACT FROM AUTHOR]