Use of Tenofovir/Emtricitabine With Immediate or Deferred Doxycycline 100mg PO Daily 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).
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- The proportion of individuals with detectable doxycycline at each study time point.
研究概览
简要总结
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.
详细描述
- 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 10.6 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% - 3.97%), 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% - 9.24%). 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Doxycycline 100mg PO daily x 12 months (Drug)
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.
干预措施: Tenofovir/emtricitabine 200/300mg PO daily (Drug)
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
干预措施: Tenofovir/emtricitabine 200/300mg PO daily (Drug)
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
干预措施: Doxycycline 100mg PO daily x 6 months (Drug)
结局指标
主要结局
The proportion of individuals with detectable doxycycline at each study time point.
时间窗: 12 months
To assess adherence of syphilis PrEP therapy
The proportion of participants who are eligible and consent to participate amongst those approached.
时间窗: 12 months
To evaluate the feasibility of recruitment for a larger study
Proportion of participants reporting > 95% adherence to both HIV and syphilis PrEP therapies
时间窗: 12 months
To assess adherence of dual HIV and syphilis PrEP therapies
The proportion of individuals reporting grade 3 or 4 adverse events in the immediate vs. deferred arms.
时间窗: 12 months
To assess the tolerability of dual HIV and syphilis PrEP therapies
The proportion of individuals with evidence of tetracycyline class resistance in common flora
时间窗: 6 and 12 months
To evaluate antimicrobial resistance over time
次要结局
- To evaluate changes in sexual activity reported by study participants over the study period.(12 months)
- To describe incidence of gonorrhea or chlamydia infection over the study period.(12 months)
- To evaluate incidence of recurrent syphilis re-infection stratified by use immediate versus deferred doxycycline PrEP.(12 months)
研究者
Jonathan Troy Grennan
Physician Lead HIV/STI Program
British Columbia Centre for Disease Control