Tenofovir/Emtricitabine With Doxycycline for Combination HIV and Syphilis Pre-exposure Prophylaxis in HIV-negative MSM

NCT02844634 | Completed Phase 4 DMC

• 1 other identifier: BritishCCDC
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Men who have sex with men remain at high risk for HIV infection. Targeting prevention interventions to MSM at highest risk of seroconversion is an important goal of combination prevention interventions. Antecedent diagnosis of another sexually transmitted infection (STI), particularly syphilis, may serve as an entry point for biomedical prevention as these individuals are at highest risk for incident HIV. The use of the antiretroviral combination of tenofovir/emtricitabine has been shown to be associated with an overall 44% reduction in HIV acquisition in high-risk MSM when taken daily as PrEP. In those individuals with detectable drug levels, the benefit was as high as 90% risk reduction. In real-world evaluations of PrEP, high-risk sexual behaviour may continue as evidenced by high rates of intercurrent sexually transmitted infections. As such, biomedical interventions that may offer additional reduction in acquisition of common sexually transmitted infections should also be evaluated. Recently a small pilot study has demonstrated potential benefit from a similar strategy for syphilis prevention. In this study 30 MSM were randomized to receive either 100mg doxycycline once daily or contingency management strategies linked to remaining free of sexually transmitted diseases at progressive study visits. Overall, those receiving doxycycline were significantly less likely to be diagnosed with any STI during followup than those in the comparator arm. The investigators therefore propose to undertake a pilot study to evaluate the feasibility of using both tenofovir/emtricitabine and doxycycline (immediate or deferred use) for pre-exposure prophylaxis amongst HIV-negative MSM with recent history of syphilis infection in Vancouver, Canada.

Conditions

HIV; Syphilis

Keywords

pre-exposure prophylaxis; men who have sex with men; HIV prevention; sexually transmitted infection; syphilis

Outcome Measures

Primary Outcomes (5)

• The proportion of participants who are eligible and consent to participate amongst those approached.

  To evaluate the feasibility of recruitment for a larger study

  12 months

• Proportion of participants reporting > 95% adherence to both HIV and syphilis PrEP therapies

  To assess adherence of dual HIV and syphilis PrEP therapies

  12 months

• The proportion of individuals with detectable doxycycline at each study time point.

  To assess adherence of syphilis PrEP therapy

  12 months

• The proportion of individuals reporting grade 3 or 4 adverse events in the immediate vs. deferred arms.

  To assess the tolerability of dual HIV and syphilis PrEP therapies

  12 months

• The proportion of individuals with evidence of tetracycyline class resistance in common flora

  To evaluate antimicrobial resistance over time

  6 and 12 months

Secondary Outcomes (3)

• To evaluate changes in sexual activity reported by study participants over the study period.

  12 months

• To evaluate incidence of recurrent syphilis re-infection stratified by use immediate versus deferred doxycycline PrEP.

  12 months

• To describe incidence of gonorrhea or chlamydia infection over the study period.

  12 months

Other Outcomes (3)

• To assess the incidence of HIV in study participants

  12 months

• To assess the incidence of doxycycline resistance in those with documented T. pallidum infection.

  12 months

• To assess the changes in the composition of the rectal microbiome

  6 and 12 months

Study Arms (2)

Immediate doxycycline 100mg PO daily

EXPERIMENTAL

Individuals will receive tenofovir/emtricitabine one tablet daily in an open-label fashion. Subjects are randomized to immediate (12 months duration) doxycycline 100mg PO daily.

Drug: Doxycycline 100mg PO daily x 12 months; Drug: Tenofovir/emtricitabine 200/300mg PO daily

Deferred doxycycline 100mg PO daily

ACTIVE COMPARATOR

Individuals will receive daily tenofovir/emtricitabine one tablet daily and will begin doxycycline 100mg PO daily after 6 months for a total duration of 6 months

Drug: Tenofovir/emtricitabine 200/300mg PO daily; Drug: Doxycycline 100mg PO daily x 6 months

Interventions

Doxycycline 100mg PO daily x 12 months DRUG

Immediate use of daily doxycycline (12 months duration, to start immediately)

Immediate doxycycline 100mg PO daily

Tenofovir/emtricitabine 200/300mg PO daily DRUG

Daily use of tenofovir/emtricitabine

Deferred doxycycline 100mg PO daily; Immediate doxycycline 100mg PO daily

Doxycycline 100mg PO daily x 6 months DRUG

Deferred use of doxycycline (6 months duration, to start 6 months post-randomization)

Deferred doxycycline 100mg PO daily

Eligibility Criteria

• Age: 19 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 19 years of age.
• Self-reported MSM status.
• Self-report condomless anal sex with a man within the last 6 months.
• HIV negative based on HIV nucleic acid amplification testing (NAT).
• Prior diagnosis of syphilis within preceding 36 months (defined on the basis of a new positive serum rapid plasma reagin (RPR) test, or ≥2-dilution rise in titre if previous syphilis, or positive darkfield microscopy result or T. pallidum direct fluorescent antibody test or PCR from a primary lesion).
• Able to provide informed consent.

You may not qualify if:

• HIV-positive individuals.
• Recent (within last 30 days) use of HIV post-exposure prophylaxis (PEP).
• Impaired renal function defined as glomerular filtration rate \< 60 mL/min.
• Chronic active Hepatitis B infection.
• History of myasthenia gravis.
• History of tetracycline/doxycycline allergy.

Sponsors & Collaborators

• British Columbia Centre for Disease Control: lead

Study Sites (1)

BC Centre for Disease Control

Vancouver, British Columbia, V5Z4R4, Canada

Location

Related Publications (2)

• Pathela P, Braunstein SL, Blank S, Shepard C, Schillinger JA. The high risk of an HIV diagnosis following a diagnosis of syphilis: a population-level analysis of New York City men. Clin Infect Dis. 2015 Jul 15;61(2):281-7. doi: 10.1093/cid/civ289. Epub 2015 Apr 13.

  PMID: 25870333 RESULT

• Bolan RK, Beymer MR, Weiss RE, Flynn RP, Leibowitz AA, Klausner JD. Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: a randomized, controlled pilot study. Sex Transm Dis. 2015 Feb;42(2):98-103. doi: 10.1097/OLQ.0000000000000216.

  PMID: 25585069 RESULT

MeSH Terms

Conditions

Syphilis; Homosexuality; Sexually Transmitted Diseases

Interventions

Doxycycline; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Communicable Diseases; Genital Diseases; Urogenital Diseases; Sexuality; Sexual Behavior; Behavior; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Troy Grennan, MD

  BC Centre for Disease Control

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Lead HIV/STI Program

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: July 26, 2016
• Study Start: May 15, 2018
• Primary Completion: May 28, 2020
• Study Completion: September 7, 2022
• Last Updated: August 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)