Chlamydia Trachomatis Infection, HIV/AIDS, HIV Infections, Neisseria Gonorrheae Infection, Syphilis Infection
Conditions
Keywords
Sexually Transmitted Infections
Brief summary
This is a randomized clinical trial of doxycycline post-exposure prophylaxis (dPEP) to reduce bacterial STIs among Kenyan women taking pre-exposure prophylaxis (PrEP). The overarching goal is to assess the effectiveness of dPEP on incidence of STIs while also balancing acceptability, cost, and impact on tetracycline resistance to inform public health policy. Participants will be randomized to receive dPEP and standard of care or the standard of care only. Questionnaires, focus group discussions, SMS, and in-depth interviews will be used to study acceptability and changes sexual behavior due to dPEP.
Detailed description
This study is an open-label 1:1 randomized clinical trial of doxycyline PEP to reduce bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and T. pallidum (syphilis) - among Kenyan women taking PrEP. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for resistance in STIs or other bacteria. The primary study objectives are to 1) evaluate the effectiveness of doxycycline PEP (dPEP) to reduce STI infections in HIV-uninfected Kenyan women taking HIV PrEP; 2) assess the safety, tolerability, and acceptability of dPEP; 3)assess adherence to dPEP; 4) investigate the impact of dPEP on tetracycline resistance in N. gonorrhoeae and C. trachomatis; 5) measure the cost of dPEP and estimate the cost per case averted, budget impact, and affordability Subjects will be randomized 1:1 to dPEP versus standard of care; randomization will be done in variable-sized blocks and using opaque envelopes opened at randomization. Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act (consistent with IPERGAY) as frequently as daily if indicated but not more than once daily. At Months 0,3,6 and 9, women randomized to dPEP will receive doxycycline, sufficient for up to daily use for 3 months (i.e., 180 capsules). Unused capsules will be counted at each quarterly follow-up visit and additional doxycycline will be provided. Participants will also be offered single- or multi-dose pill carriers for ease of dosing dPEP following exposures. All participants will receive quarterly visits for standard of care prevention services and collection of clinical and behavioral data, for a total of 12 months of follow-up.
Interventions
DRUGDoxycycline
200 mg of doxycycline to be taken orally within 24 hours and up to 72 hours after each condomless sex act
Sponsors
Kenya Medical Research Institute
Kenya National AIDS & STI Control Programme
University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to give written informed consent * Age ≥18 years and ≤30 years old * Female sex at birth * HIV-seronegative at the time of last test within the past month and a current prescription for PrEP according to the national guidelines of Kenya (define PrEP eligibility as: partner of HIV-infected person not on ART or on ART for \<6 months, \>1 partner of unknown status, transactional sex, recent STI, recurrent HIV PEP use, inconsistent condom use, or injection drug use).
Exclusion criteria
* Pregnant * Breastfeeding a child * Allergy to tetracycline class * Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, phenytoin, and warfarin. * Recent use of prolonged (more than 14 day course) antibiotics in the month prior to enrollment * Active, clinically significant medical or psychiatric conditions that would interfere with study participation, at the discretion of the site investigator or designee.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis | 12 months post enrolment | Combined incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by by laboratory-based diagnosis (e.g., positive N. gonorrhoeae or C. trachomatis based on NAAT or syphilis based on four-fold increase in non-treponemal titers). |
Countries
Kenya
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| dPEP Intervention Arm Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act
Doxycycline: 200 mg of doxycycline to be taken orally within 24 hours and up to 72 hours after each condomless sex act | 224 |
| Standard of Care Arm Participants assigned to Standard of Care | 225 |
| Total | 449 |
Baseline characteristics
| Characteristic | dPEP Intervention Arm | Standard of Care Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 9 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 209 Participants | 216 Participants | 425 Participants |
| Age, Continuous | 24 years | 24 years | 24 years |
| Race/Ethnicity, Customized Black/African | 224 Participants | 225 Participants | 449 Participants |
| Region of Enrollment Kenya | 224 Participants | 225 Participants | 449 Participants |
| Sex: Female, Male Female | 224 Participants | 225 Participants | 449 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 224 | 0 / 225 |
| other Total, other adverse events | 40 / 224 | 12 / 225 |
| serious Total, serious adverse events | 0 / 224 | 0 / 225 |
Outcome results
Primary
Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis
Combined incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by by laboratory-based diagnosis (e.g., positive N. gonorrhoeae or C. trachomatis based on NAAT or syphilis based on four-fold increase in non-treponemal titers).
Time frame: 12 months post enrolment
Population: Intention to treat, STI incidence events per 100 person-years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| dPEP Intervention Arm | Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis | 25.1 Events per 100 person-years |
| Standard of Care Arm | Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis | 29.0 Events per 100 person-years |