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Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention

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Abstract

Tenofovir-based regimens as pre-exposure prophylaxis (PrEP) are highly effective at preventing HIV infection. The most common side-effect is gastrointestinal (GI) distress which may be associated with changes in the microbiome. Dysbiosis of the microbiome can have numerous health-related consequences. To understand the effect of PrEP on dysbiosis, we evaluated 27 individuals; 14 were taking PrEP for an average of 171 weeks. Sequencing of 16S rRNA was performed using self-collected rectal swabs. Mixed beta diversity testing demonstrated significant differences between PrEP and non-PrEP users with Bray–Curtis and unweighted UniFrac analyses (p = 0.05 and 0.049, respectively). At the genus level, there was a significant reduction in Finegoldia, along with a significant increase in Catenibacterium and Prevotella in PrEP users. Prevotella has been associated with inflammatory pathways, insulin resistance and cardiovascular disease, while Catenibacterium has been associated with morbid obesity and metabolic syndrome. Overall, these results suggest that PrEP may be associated with some degree of microbiome dysbiosis, which may contribute to GI symptoms. Long-term impact of these changes is unknown.

Resumen

Los regímenes basados en tenofovir como profilaxis previa a la exposición (PPrE) son muy eficaces en prevenir la infección por VIH. El efecto secundario más común es el malestar gastrointestinal (GI) que puede estar asociado con cambios en el microbioma. La disbiosis del microbioma puede tener numerosas consecuencias relacionadas con la salud. Para comprender el efecto de la PPrE sobre la disbiosis, evaluamos a 27 individuos; 14 de los individuos tomaron PPrE durante un promedio de 171 semanas. La secuenciación del ARNr 16S se realizó utilizando hisopos rectales recolectados por los propios pacientes. Las pruebas beta de diversidad mixta demostraron diferencias significativas entre los usuarios de PPrE y los que no utilizaron PPrE al analizarlos mediente Bray–Curtis y UniFrac no ponderados (p = 0,05 y 0,049, respectivamente). A nivel de género, hubo una reducción significativa de Finegoldia, junto con un aumento significativo de Catenibacterium y Prevotella en usuarios de PPrE. Prevotella se ha asociado con trayectorias inflamatorias, resistencia a insulina y enfermedades cardiovasculares, mientras que Catenibacterium se ha asociado con enfermedades como obesidad mórbida y padecimientos de síndrome metabólico. En general, estos resultados sugieren que la PPrE puede estar asociada con cierto grado de disbiosis del microbioma, lo que puede contribuir a los síntomas gastrointestinales. El impacto a largo plazo de estos cambios se desconoce.

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Funding

P.B. and EH were supported by the U.S. Department of Defense through the Peer Reviewed Medical Research Program under award number W81XWH-18-1-0198, by the National Center for Complementary & Integrative Health of the NIH Award Number R21AT010366, and by institutional development awards P20GM121344 received from the National Institute of General Medical Sciences. The funding agencies had no role in the design of the study or the collection, analysis, and interpretation of data. The authors would like to specifically thank Caroline Keroack for her thoughtful feedback during the editing process.

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Author notes

  1. Bryce K. Perler and Elizabeth M. Reinhart have contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Bryce K. Perler

  2. Department of Molecular Microbiology and Immunology, Brown University, Providence, USA

    Elizabeth M. Reinhart & Peter Belenky

  3. Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, USA

    Madeline Montgomery & Philip A. Chan

  4. Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, USA

    Michaela Maynard & Philip A. Chan

  5. Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Warren Alpert Medical School of Brown University, Providence, USA

    Jason M. Shapiro

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  1. Bryce K. Perler
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by BKP, PAC, JS, MM, and PB. Data collection was performed by BKP, MM and MM. Data analysis was performed by BKP and EMR. The first draft of the manuscript was written by BKP and EMR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Bryce K. Perler or Peter Belenky.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical Approval

The study was reviewed and approved by the Institutional Review Board of The Miriam Hospital, a Lifespan affiliated hospital. All procedure performed in the studies involving human subjects were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individuals participants including in the study.

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Supplementary Information

Below is the link to the electronic supplementary material.

10461_2020_3130_MOESM1_ESM.docx

Supplemental File 1: Survey. This 17-point questionnaire obtained demographic, lifestylebehavioral, and sexual practice information from each participant over the past 3 months leadingup to enrollment. (DOCX 20 kb)

Supplemental File 2: Raw Read Counts. The number of raw reads per sample after 16S rRNAsequencing. (XLSX 9 kb)

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Perler, B.K., Reinhart, E.M., Montgomery, M. et al. Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention. AIDS Behav 25, 2005–2013 (2021). https://doi.org/10.1007/s10461-020-03130-7

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