Long-Term HIV Pre-Exposure Prophylaxis May Induce Significant Microbiome Shifts

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Changes in microbiome balance were not associated with variable factors such as age, race, PrEP duration, tenofovir diphosphate blood level, and drug use.
Changes in microbiome balance were not associated with variable factors such as age, race, PrEP duration, tenofovir diphosphate blood level, and drug use.

Long-term pre-exposure prophylaxis (PrEP) is associated with enteric microbiome dysbiosis, in which levels of the bacterial genus Streptococcus decrease while levels of the bacterial family Erysipelotrichaceae increase, according to a study published in Scientific Reports.

The investigators of this study sought to examine the effect of daily HIV PrEP with tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC) on the enteric microbiome profiles of healthy individuals absent of HIV infection.

The study investigators analyzed serial specimens from 8 healthy individuals with long-term PrEP adherence who participated in the California Collaborative Treatment Group study 595, a randomized controlled trial involving high-risk transgender women and men who have sex with men (MSM).

Microbiota specimens were collected through rectal swab prior to initiating PrEP and 48 to 72 weeks after adherent PrEP.

To identify microbiome shifts, researchers assessed the relative abundance of each bacterial family and genus using next-generation gene sequencing of the 16S ribosomal RNA both before and after daily PrEP administration.

The overall microbial diversity of each participant was comparable both before and after 48 to 72 weeks of daily PrEP.

Gene sequencing of the V4 region of the 16S ribosomal RNA revealed that the presence of Streptococcus significantly reduced, from 12% to 1.2% (P =.036), and at the family level, Erysipelotrichaceae significantly increased, from 0.79% to 3.3% (P =.028).

Study investigators performed long-read sequencing in order to pinpoint which species of Streptococcus and Erysipelotrichaceae were significantly affected by long-term PrEP: The results showed Streptococcus agalactiae, Streptococcus oralis, Streptococcus mitis were reduced, but Catenibacterium mitsuokai, Holdemanella biformis, and Turicbacter sanguinis of the Erysipelotrichaceae family increased.

Changes in microbiome balance were not associated with variable factors such as age, race, PrEP duration, tenofovir diphosphate blood level, and drug use. These results suggested that microbiome shifts were likely induced by daily PrEP.

This study was limited by a small population size, and future studies should examine microbiome shifts in a large cohort with long-term outcomes. 

The study investigators concluded that long-term PrEP contributed to significant shifts at both the family and genus levels of the enteric microbiome; Streptococcus levels decreased and Erysipelotrichaceae increased following a daily TDF-FTC regimen. By characterizing the microbiota signatures and side effects of PrEP, adherence may be improved, thus helping prevent HIV infection.

Disclosure: One author declares associations with the pharmaceutical industry. Please see original reference for a full list of authors' disclosures.

Reference                    

Dubé MP, Park SY, Ross H, Love TMT, Morris SR, Lee HY. Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota [published online October 12, 2018]. Sci Rep. doi:10.1038/s41598-018-33524-6

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