This study is being done to test the effects of doxycycline on inflammation and the bacteria in the body in people with HIV and in people on HIV pre-exposure prophylaxis. This drug is approved by the Food and Drug Administration (FDA) for the treatment of bacterial infections. The study team will investigate whether the drug has additional effects on inflammation or on the bacteria that live in the body.
This project aims to determine the potential anti-inflammatory and microbiome effects of doxycycline when used as post-exposure prophylaxis (Doxy PEP) for sexually transmitted infections (STIs). This study is important in the field of research because it allows the investigators to define the systemic and gut anti-inflammatory, microbiome, and resistome effects of doxycycline when used as post-exposure prophylaxis (Doxy PEP) for sexually transmitted infections. The study population that this study seeks to enroll consists of healthy people assigned male at birth, with and without HIV, who are willing to undergo study procedures. Study procedures will include the collection of medical history, as well as biological specimen sampling, such as blood and rectal tissue biopsies. The duration of this clinical trial for study participants will be approximately 12 weeks. This will include five in-person visits lasting about 45 minutes to 1 hour (including two biopsy visits). This study will utilize data specimen banking for future research.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
200
Doxycycline monohydrate 200 mg (two 100 mg tablets) is used to treat or prevent infections that are strongly suspected to be caused by bacteria. Doxycycline monohydrate is an antimicrobial drug indicated for the treatment of bacterial infections, including sexually transmitted diseases. Centers for Disease Control and Prevention (CDC) recommends its use as post-exposure prophylaxis (PEP). Blood and rectal mucosal samples will be collected before doxycycline is initiated. Participants will be instructed to take 200 mg of doxycycline by mouth every Monday, Wednesday, and Friday. Additional doses of doxycycline will be permitted on other days if sex without a condom occurs per CDC guidance. After 12 weeks of at least three-weekly doxycycline, blood and rectal mucosal samples will be collected for immunologic and microbiome/resistome assays.
Standard of care. Blood and rectal mucosal samples.
Grady Health System (non-CRN)
Atlanta, Georgia, United States
RECRUITINGHope Clinic
Atlanta, Georgia, United States
RECRUITINGComposite inflammation score
A composite inflammation score in the blood and rectal secretions before and after doxy-PEP will be calculated for each participant: +1 point for each proinflammatory cytokine (IP-10, IL-1β, tumor necrosis factor (TNF-α), Monocyte chemoattractant protein-1 (MCP-1), IL-17A, IL-6, interferon (IFN-γ), IL-12p70, IL-8) that was in the top quartile concentration and -1 point for each anti-inflammatory cytokine (IL-4, IL-10), T-cell growth factor (TGF-β1) that was in the top quartile concentration for a maximum score of 9 and minimum score of -3.
Time frame: Baseline and 12 weeks after the start of doxycycline administration
Tetracycline (TCN) Gene Abundance
TCN gene-level abundance will be normalized using reads per kilobase per genome equivalent (RPKG), calculated from filtered contigs and estimated genome equivalents (MicrobeCensus). RPKG values will be summed by resistance class, sub-class (e.g., inactivation, target modification, efflux), and by host assignment (pathogen vs. commensal). Group differences in mean TCN RPKG values will be evaluated using non-parametric permutation tests.
Time frame: Baseline and 12 weeks after the start of doxycycline administration
Estimated mass of antimicrobial resistance (AMR) Genes
To benchmark normalized abundance, the mass of AMR genes will be estimated using spike-in controls (ZymoBIOMICS). This will provide a quantitative measure of the total AMR gene burden per sample. Group differences in total AMR gene mass will be tested using non-parametric permutation tests.
Time frame: Baseline and 12 weeks after the start of doxycycline administration
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