Document text
Principal Investigator: Matthew A. Spinelli
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $781,821
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ ABSTRACT
Rates of bacterial sexually transmitted infections (STIs) are rising globally, demanding innovative
interventions beyond the scope of current efforts to prevent STIs. While HIV pre-exposure prophylaxis (PrEP)
effectively reduces HIV acquisition risk, it does not address the surge in bacterial STIs. The DoxyPEP Study
has demonstrated the efficacy of Doxycycline post-exposure prophylaxis (PEP) among men who have sex with
men (MSM) and transgender women. However, puzzlingly, doxycycline PEP was found ineffective in cisgender
women in the dPEP study, despite doxycycline achieving similar concentrations in the vagina and rectum.
Preliminary data from dPEP show low detection of doxycycline among participants, suggesting that low
medication adherence may explain the null result. To fully interpret the dPEP study and others, in-depth
adherence measurement techniques for doxycycline will need to be developed.
As was needed for HIV PrEP to establish the relationship between patterns of pill-taking and drug
concentrations, a directly observed therapy (DOT) study, the gold-standard approach to determine the
pharmacology of doxy and establish pill-taking cut-offs, is needed (Aim 1). We will enroll 36 participants (12
cisgender men, 12 cisgender women, and 12 transgender women) for a randomized cross-over DOT study,
with in-depth pharmacokinetic measurement while dosing and during washout. When combined with sexual
behavior data in the trials conducted in MSM/TGW and cisgender women, doxycycline PEP coverage of sexual
acts and pharmacodynamic relationships can be established. These data can be used to understand patterns
of adherence over time among women in dPEP to interpret the null study, and to understand the relationship
between cumulative adherence and STI incidence reduction (Aim 2). We will then examine adherence patterns
in the recently completed DoxyPEP study to understand the potential clinical role of a urine or plasma metric
amenable to point-of-care test development to identify doxy-PEP adherence challenges (Aim 3). Finally, this
work will establish thresholds of doxy levels in hair, urine, and plasma to interpret doxy adherence in roll-out
studies in the future.
By study end, we will have determined dosing cut-offs for doxy in hair, plasma, and urine, and will use these
cut-offs to examine the relationship between adherence patterns and STI reduction in the dPEP study, and
adherence predictors and metrics within the DoxyPEP trial. These benchmarks and pharmacodynamic
analyses will establish adherence metrics for current and future rollout studies of doxy-PEP.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adherence><Anti-Retroviral Agents><Aquadiol><Assay><Benchmarking><Best Practice Analysis><Bioassay><Biological Assay><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Sample><Blood specimen><Caring><Clinical><Clinical Trials><Collection><Congenital Syphilis><Data><Data Bases><Databases><Detection><Development><Diagnostic><Dimenformon><Diogyn><Diogynets><Directly Observed Therapy><Dose><Doxycycline><Drug Kinetics><Drugs><Dryness><Enrollment><Epidemic><Estrace><Estradiol><Estradiol-17 beta><Estradiol-17beta><Estraldine><Estrogens><Frequencies><Future><Gender><HIV><Hair><Health><High-Risk Sex><Human Immunodeficiency Viruses><Immunoassay><Incidence><Intervention><Intervention Strategies><Knowledge><LAV-HTLV-III><Laboratories><Lymphadenopathy-Associated Virus><MSM><Measurement><Measures><Medication><Methods><Modeling><Ovocyclin><Ovocylin><Participant><Patient Self-Report><Pattern><Performance><Persons><Pharmaceutical Preparations><Pharmacodynamics><Pharmacokinetics><Pharmacology><Plasma><Plasma Serum><PrEP><Prevention><Progynon><Prophylactic treatment><Prophylaxis><Randomized><Rectum><Reporting><Reticuloendothelial System, Serum, Plasma><Risk><Role><STD prevention><STI prevention><Sampling><Self-Report><Sex Behavior><Sexual Activity><Sexual Behavior><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Spottings><Techniques><Tenofovir><Testing><Therapeutic Estradiol><Therapeutic Estrogen><Time><Unprotected Sex><Unsafe Sex><Urine><Vagina><Venereal Diseases><Venereal Disorders><Venereal Infections><Vibramycin><Viread><Virus-HIV><Visit><Woman><Work><alpha-6-Deoxyoxytetracycline><anti-retroviral><behavior adherence><behavioral adherence><benchmark><cis-female><cis-gender man><cis-gender woman><cis-male><cis-man><cis-woman><cisgender man><cisgender woman><clinical predictors><cohort><compliance behavior><condomless intercourse><condomless sex><condoms><cost><data base><demographics><design><designing><developmental><drug adherence><drug compliance><drug/agent><effective intervention><enroll><gender affirmation hormone therapy><gender affirmation hormone treatment><gender affirming hormone therapy><gender affirming hormone treatment><infection rate><innovate><innovation><innovative><intervention arm><interventional strategy><medication adherence><medication compliance><men having sex with men><men who have sex with men><men who have sex with other men><pharmacologic><pill><point of care><point of care testing><pre-exposure prophylaxis><prevent sexually transmitted disease><prevent sexually transmitted infections><randomisation><randomization><randomly assigned><rate of infection><screening><screenings><sex><sex activity><sexual activities><sexually acquired infection><sexually transmitted disease prevention><sexually transmitted infection prevention><social role><statistics><time use><trans-women><transgender women><transwoman><transwomen><treatment arm><trend><unprotected intercourse>