Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis

Jennifer A Fulcher; Fan Li; Ryan R Cook; Sara Zabih; Alexander Louie; Hideaki Okochi; Nicole H Tobin; Monica Gandhi; Steven Shoptaw; Pamina M Gorbach; Grace M Aldrovandi

doi:10.1093/ofid/ofz463

Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis

Open Forum Infect Dis. 2019 Oct 29;6(11):ofz463. doi: 10.1093/ofid/ofz463. eCollection 2019 Nov.

Authors

Jennifer A Fulcher^{1

2}, Fan Li³, Ryan R Cook⁴, Sara Zabih³, Alexander Louie⁵, Hideaki Okochi⁵, Nicole H Tobin³, Monica Gandhi⁵, Steven Shoptaw⁶, Pamina M Gorbach^{1

4}, Grace M Aldrovandi³

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
² VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.
³ Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁴ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California, USA.
⁵ Division of HIV, Infectious Diseases, and Global Medicine (Hair Analytical Laboratory), Department of Medicine, University of California, San Francisco, California, USA.
⁶ Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Abstract

Background: Oral daily tenofovir (TFV) disoproxil fumarate/emtricitabine (TDF/FTC) for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is highly effective for HIVprevention, yet long-term effects are not fully understood. We investigated the effects of PrEP on the rectal microbiome in a cohort of men who have sex with men (MSM).

Methods: This cross-sectional analysis included HIV-negative MSM either on PrEP (n = 37) or not (n = 37) selected from an ongoing cohort using propensity score matching. Rectal swabs were used to examine microbiome composition using 16S ribosomal ribonucleic acid gene sequencing, and associations between PrEP use and microbiota abundance were examined. Hair specimens were used to quantify TFV and FTC exposure over the past 6 weeks on a subset of participants (n = 15).

Results: Pre-exposure prophylaxis use was associated with a significant increase in Streptococcus abundance (adjusted P = .015). Similar associations were identified using least absolute shrinkage and selection operator (LASSO) regression, confirming the increase in Streptococcus and also showing increased Mitsuokella, Fusobacterium, and decreased Escherichia/Shigella. Increased Fusobacterium was significantly associated with increasing TFV exposure.

Conclusions: Oral TDF/FTC for PrEP is associated with rectal microbiome changes compared to well matched controls, specifically increased Streptococcus and Fusobacterium abundance. This study highlights the need for future investigations of the role of microbiome changes on HIV susceptibility and effectiveness of PrEP.

Keywords: men who have sex with men (MSM); pre-exposure prophylaxis (PrEP); rectal microbiome.

Abstract

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