Sexually Transmitted Diseases
Conditions
Keywords
Post-Exposure Prophylaxis, HIV, STI, PEP, Prevention
Brief summary
The study will determine tissue pharmacology of a single dose of doxycycline for sexually transmitted infection (STI) Post-exposure Prophylaxis (PEP).
Detailed description
To determine tissue pharmacology of a single dose of doxycycline for STI PEP, investigators at Emory University will collaborate with the Centers for Disease Control and Prevention (CDC) to conduct a clinical trial of up to 20 men who have sex with men (MSM) and women aged 18-59, with measurement of anti-retroviral drug and doxycycline concentrations in the rectum and vaginal regions.
Interventions
DRUGDoxycycline
Doxycycline (DOX \[200 mg\]) is an oral medication used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections.
DRUGBiktarvy
Biktarvy (200mg) is an oral combination anti-HIV medication that contains the drugs tenofovir alafenamide, emtricitabine, and bictegravir.
Sponsors
Centers for Disease Control and Prevention
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
1. HIV negative person, who was assigned male or female at birth, who reports sex with another man in the last year and is in good general health 2. Aged 18-59 years 3. Not currently taking PrEP and no plans to initiate during study 4. Not currently taking PEP 5. Not currently taking doxycycline or other tetracycline-derived antibiotics and no plans to initiate during the study 6. Willing to use condoms consistently for the duration of the study 7. Able to provide informed consent in English 8. No plans for relocation in the next 4 months 9. Willing to undergo peripheral blood, urine, rectal or vaginal secretion collection, and a rectal or vaginal and cervical biopsy procedure 10. Willing to use study products as directed 11. Hepatitis B surface antigen (HBsAg) negative (screening lab test) 12. Creatinine clearance \>60 ml/min
Exclusion criteria
1. Currently infected with hepatitis virus and/ or has liver disease 2. Current or chronic history of kidney disease or creatinine clearance (CrCl)\<60 ml/min 3. Continued need for, or use during the 90 days prior to enrollment, of the following medications: 1. Systemic immunomodulatory agents 2. Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators) 3. Chemotherapy or radiation for treatment of malignancy 4. Experimental medications, vaccines, or biologicals 4. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures 5. Intent to use doxycycline or other tetracycline-derived antibiotics during the course of the study, outside of the study procedures 6. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements 7. Not pregnant and no plans on getting pregnant throughout the duration of the study 8. Known allergic reaction to study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rectal Doxycycline Concentration | 24 hours after a single dose | Doxycycline concentration in tissue from a rectal biopsy was measured. Rectal biopsies were obtained from men. Women had the option to provide a rectal tissue sample. |
| Vaginal Doxycycline Concentration | 24 hours after a single dose | Doxycycline concentration in tissue from a vaginal biopsy was measured. |
| Plasma Doxycycline Concentration | 24 hours after a single dose | Doxycycline concentration in plasma was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rectal Bictegravir Concentration | 24 hours after a single dose | Bectegravir concentration in tissue from a rectal biopsy was measured. |
| Vaginal Bictegravir Concentration | 24 hours after a single dose | Bictegravir concentration in tissue from a vaginal biopsy was measured. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Hope Clinic in Atlanta, Georgia, USA. Participant enrollment began May 20, 2021 and all follow-up assessments were completed by May 9, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline and Biktarvy Participants took both study drugs simultaneously at home and came to the clinic for a study visit the following day for samples to be obtained 24 hours after the single dose of study drugs. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | Doxycycline and Biktarvy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Plasma Doxycycline Concentration
Doxycycline concentration in plasma was measured.
Time frame: 24 hours after a single dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline and Biktarvy | Plasma Doxycycline Concentration | 487 µg/mL |
Primary
Rectal Doxycycline Concentration
Doxycycline concentration in tissue from a rectal biopsy was measured. Rectal biopsies were obtained from men. Women had the option to provide a rectal tissue sample.
Time frame: 24 hours after a single dose
Population: This analysis includes participants who completed the rectal biopsy during the 24-hours post-dose visit. Ten men and 5 women provided rectal tissue samples at the 24-hours post-dose visit. One male attended the visit but was not able to tolerate the biopsy procedure and no rectal tissue was obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline and Biktarvy | Rectal Doxycycline Concentration | 0.654 µg/g |
Primary
Vaginal Doxycycline Concentration
Doxycycline concentration in tissue from a vaginal biopsy was measured.
Time frame: 24 hours after a single dose
Population: One female attended the visit 24 hours post-dose but was not able to proceed with the vaginal biopsy procedure due to menses and vaginal rugae.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline and Biktarvy | Vaginal Doxycycline Concentration | 0.367 µg/g |
Secondary
Rectal Bictegravir Concentration
Bectegravir concentration in tissue from a rectal biopsy was measured.
Time frame: 24 hours after a single dose
Population: This analysis includes participants who completed the rectal biopsy during the 24-hours post-dose visit. Ten men and 5 women provided rectal tissue samples at the 24-hours post-dose visit. One male attended the visit but was not able to tolerate the biopsy procedure and no rectal tissue was obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline and Biktarvy | Rectal Bictegravir Concentration | 0.085 µg/g |
Secondary
Vaginal Bictegravir Concentration
Bictegravir concentration in tissue from a vaginal biopsy was measured.
Time frame: 24 hours after a single dose
Population: One female attended the visit 24 hours post-dose but was not able to proceed with the vaginal biopsy procedure due to menses and vaginal rugae.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline and Biktarvy | Vaginal Bictegravir Concentration | 0.207 µg/g |