Clinical Trials

MainTitle

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

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified August 2016 by Jonathan Troy Grennan, British Columbia Centre for Disease Control

Sponsor
British Columbia Centre for Disease Control


Information provided by (Responsible Party)
Jonathan Troy Grennan, British Columbia Centre for Disease Control

ClinicalTrials.gov Identifier
NCT02844634

First received: July 22, 2016
Last updated: August 4, 2016
Last Verified: August 2016
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV
Syphilis

Drug : Doxycycline 100mg PO daily x 12 months
Drug : Tenofovir/emtricitabine 200/300mg PO daily
Drug : Doxycycline 100mg PO daily x 6 months
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Tenofovir/Emtricitabine With Immediate or Deferred Daily Doxycycline for Combination HIV and Syphilis Pre-exposure Prophylaxis in HIV-negative Men Who Have Sex With Men: a Pilot Study of Dual Daily HIV and Syphilis PrEP. (The DuDHS Trial).

Further study details as provided by Jonathan Troy Grennan, British Columbia Centre for Disease Control:

Primary Outcome Measures

  • To assess adherence to long-term HIV PrEP use. [ Time Frame: 12 months ]
    Proportion of individuals completing 12 months of tenofovir/emtricitabine
  • To assess feasibility of using daily doxycycline for syphilis PrEP: [ Time Frame: 12 months ]
    Proportion of individuals successfully completing six and 12 month prophylaxis period. Adherence to doxycycline over the assigned study period.
  • To evaluate the tolerability of daily doxycycline. [ Time Frame: 12 months ]
    To assess self-reported side effects on daily doxycycline, and side-effect related discontinuations
Secondary Outcome Measures:
  • To evaluate changes in sexual activity reported by study participants over the study period. [ Time Frame: 12 months ]
  • To evaluate syphilis re-infection rates over a 12 month period stratified by use of doxycycline for PrEP. [ Time Frame: 12 months ]
  • To describe frequency of other STI's diagnosed in study participants over the study period. [ Time Frame: 12 months ]
Other Outcome Measures:
  • Change in tetracycline resistance in S.aureus nasal isolates [ Time Frame: 12 months ]
    To assess carriage rate of nasal S.aureus at beginning and end of the study period and to determine proportion of isolates with tetracycline resistance

Estimated Enrollment: 50
Study Start Date: September 2016
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Immediate doxycycline 100mg PO daily
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

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

Drug: Tenofovir/emtricitabine 200/300mg PO daily

Daily use of tenofovir/emtricitabine

Active Comparator: Deferred doxycycline 100mg PO daily
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

Daily use of tenofovir/emtricitabine

Drug: Doxycycline 100mg PO daily x 6 months

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

Detailed Description:

  1. Rationale: 1.1 Men who have sex with men with antecedent diagnosis of another sexually transmitted infection, particularly syphilis, are at high risk for HIV infection.

Men who have sex with men (MSM) continue to experience high rates of HIV incident infections in Canada and a disproportionately high burden of disease relative to the general population. In 2011, approximately 48% of new diagnoses occurred in MSM across Canada, a figure that has been relatively stable for the last decade. Within British Columbia (BC), although HIV new diagnosis rates overall have been declining over the last decade (dropping from a rate of
  • 6 cases/100,000 in 2004 to 5.9 cases/100,000 in 2013), MSM made up an increasing majority of new diagnoses (59%) within BC in 2013. Within Vancouver Coastal Health Authority (VCH), approximately 70% of all new HIV diagnoses annually from 2012-15 were amongst MSM.

  • Targeting prevention interventions to MSM at highest risk is important when determining potential publicly funded biomedical interventions, particularly the use of HIV pre-exposure prophylaxis (PrEP). Antecedent diagnosis of another sexually transmitted infection (STI) may serve as an entry point for biomedical prevention as these individuals are at highest risk for incident HIV. In an evaluation of HIV incidence following diagnosis of syphilis infection in New York City, the annual HIV incidence was 3.6% (95% Confidence Interval [CI]: 3.27% -
  • 97%), with overall HIV incidence amongst MSM of 5.56% (1). In those males with syphilis and a subsequent additional STI the HIV incidence was even greater at 7.89% (95% CI: 6.62% -
  • 24%). A similar analysis of clients attending STI clinics in BC has revealed that antecedent STI is predictive of an elevated risk for subsequent HIV seroconversion with clients who ever had a diagnosis of syphilis having an HIV incidence of 3.6% person-years (95%CI: 2.5-4.9), gonorrhea (2.0%; 95%CI: 1.6-2.5), rectal gonorrhea (4.5% person-years; 95%CI: 3.4-5.8), while individuals with rectal gonorrhea and syphilis had an incidence rate of 12.6 % person-years (95%CI: 8.4-21.8).

  • Evaluating the use of PrEP in MSM with antecedent STI is an important component to inform HIV prevention programs in BC and nationally. The STI clinics operated by the BC Centre for Disease Control are well-positioned for this evaluation as about 15 and 25% of all HIV diagnoses in BC and VCH, respectively are diagnosed at these clinics.
  • 2. STI prevention strategies may also benefit from biomedical prevention interventions

  • Novel biomedical strategies have been shown to be effective in preventing acquisition of STI such as HIV, and are now considered to be standard of care for at-risk MSM in the United States. 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 STI (50% of PrEP users after 12 months in a study of 657 PrEP initiators in San Francisco). As such, biomedical interventions that may offer additional reduction in acquisition of common sexually transmitted infections should be evaluated.
    Recently a small pilot study has demonstrated potential benefit from a similar strategy for syphilis prevention (2). 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. Doxycycline 100mg daily was chosen based on prior studies indicating that doses as low as once weekly doxycycyline could serve as prophylaxis for leptospirosis, another spirochete infection.
    Overall, those receiving doxycycline were significantly less likely to be diagnosed with any STI during follow-up than those in the comparator arm (odds ratio [OR] 0.27; 95% CI 0.09 -
  • 83). Specific protection against syphilis infection was not seen during the on-treatment phase (OR 0.27; 95% CI 0.04 - 1.73), possibly reflecting the small sample size. During the study period, no change in sexual behaviours between arms was noted, supporting the potential role of doxycycline prophylaxis. A larger pilot evaluation of this strategy, in combination with HIV PrEP, would be a novel syndemic approach to addressing both the HIV and syphilis burden amongst the highest risk MSM.

  • The investigators therefore propose to undertake a randomized trial of immediate vs. deferred doxycycline in conjunction with daily tenofovir/emtricitabine to determine the feasibility of combined HIV and syphilis pre-exposure prophylaxis amongst HIV-negative MSM with recent history of syphilis infection in Vancouver, Canada.
  • Objectives:
    1. To assess feasibility of using dual daily PrEP. Defined as:
      1. Proportion of individuals successfully completing 12 months of tenofovir/emtricitabine
      2. Proportion of individuals successfully completing six and 12 months of doxycycline.
    2. To evaluate the adherence and tolerability of daily dual PrEP in at-risk MSM.
    3. To evaluate changes in sexual activity reported by study participants over the study period.
    4. To evaluate HIV incidence and syphilis re-infection rates over a 12 month period stratified by use of doxycycline for PrEP.
    5. To describe frequency of other STI's diagnosed in study participants over the study
    period.

    Eligibility

    Eligibility

    Ages Eligible for Study: 19 Years and older  
    Sexes Eligible for Study: Male  
    Accepts Healthy Volunteers: No  

    Criteria

    Inclusion Criteria:

    • Self-reported MSM status.
    • HIV negative based on HIV Nucleic Acid Amplification (NAT) testing.
    • Recent diagnosis of syphilis within preceding 36 months (defined on the basis of positive serum rapid plasma reagin (RPR) test, or positive darkfield microscopy result or T.pallidum direct fluorescent antibody test from a primary lesion).
    • Able to provide informed consent.


    Exclusion Criteria:
    • HIV-positive individuals.
    • Recent (within 30 days) use of HIV post-exposure prophylaxis (any regimen).
    • Recent (within 30 days) use of HIV pre-exposure prophylaxis with tenofovir-emtricitabine or PrEP study drug.
    • Glomerular filtration rate < 60 mL/min.
    • Chronic active Hepatitis B infection.
    • History of intolerance/allergy or adverse reaction to any component of tenofovir/emtricitabine.
    • History of tetracycline/doxycycline allergy.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02844634

    Contacts

    Contact:   Troy Grennan, MD 604 707 5606 troy.grennan@bccdc.ca
    Contact:   Mark W Hull, MD 604 806 8640 mhull@cfenet.ubc.ca

    Sponsors and Collaborators

    British Columbia Centre for Disease Control

    Investigators

    Principal Investigator: Troy Grennan, MD BC Centre for Disease Control
    More Information

    More Information


    Responsible Party: Jonathan Troy Grennan, Physician Lead HIV/STI Program, British Columbia Centre for Disease Control  
    ClinicalTrials.gov Identifier: NCT02844634   History of Changes  
    Other Study ID Numbers: BritishCCDC  
    Study First Received: July 22, 2016  
    Last Updated: August 4, 2016  
    Individual Participant Data    
    Plan to Share IPD: No  

    Keywords provided by Jonathan Troy Grennan, British Columbia Centre for Disease Control:

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

    Additional relevant MeSH terms:
    Syphilis
    Tenofovir
    Emtricitabine
    Doxycycline

    ClinicalTrials.gov processed this data on December 15, 2017
    This information is provided by ClinicalTrials.gov.