Doxycycline

for Sexually
Transmited
Infection
(STI)
Prevention
Dr. Sheena Ward, PharmD, MSHI
2023 InpharmD Fellow
 Objectives

Discuss STI Review

Review and
epiemiology and Review IPERGAY Department of
interpet DoxyPEP
incidence in the study Public Health
Study
US Recommendations

1 2 3 4
 STI Epidemiology and Incidence
In the United States

STI Epidemiology Incidence

~ ½ of new
In 2018 1 in ~ $16 billion Chlamydia Gonorrhea Syphillis
infections occur
5 people in medical reported reported reported
in youth 15-24
have an STI costs 2012-2021 2012-2021 2012-2021
years old
26 million STIs Chlamydia, 8 pathogens linked to Between 2020 and Rate of primary and
Rates are
acquired gonorrhea, and greatest incidence 2021 the increase secondary syphillis
in rates followed a consistently
annually syphillis increasing since have increased
combined signifigant decrease consistentantly with
in rates from 2019 - 2012 with higher higher rates in men
account for $1.1 rates in men than
2020 compared to women
billion women
 Chlamydia — Rates of Reported Cases by
Sex, United States, 2012–2021

[5] Figures [Internet]. www.cdc.gov.2023. Available from: https://www.cdc.gov/std/statistics/2021/figures.htm

 Gonorrhea — Rates of Reported
Cases by Sex, United States,
2012–2021

[5] Figures [Internet]. www.cdc.gov.2023. Available from: https://www.cdc.gov/std/statistics/2021/figures.htm

 Primary and Secondary Syphilis — Reported
Cases by Sex and Sex of Sex Partners, United
States, 2017–2021

[5] Figures [Internet]. www.cdc.gov.2023. Available from: https://www.cdc.gov/std/statistics/2021/figures.htm

 IPERGAY Trial
Design:
• Open-label randomized study
• N= 232

Objective: To assess doxycycline as post exposure prophylaxis of chlamydia, gonorrhea and

syphillis

Population:
HIV-negative men (MSM) or transgender women (TSW) having sex with men, aged 18
years or older, and at high risk for HIV acquisition were eligible for inclusion

Methods:
• Randomized 1:1 to receive doxycycline PEP 200 mg w/in 24hrs after sex vs. no PEP
• Limited DoxyPEP up to max of 3X/week

Findings:
First STI occurrence lower in PEP vs. no PEP. Significant ↓ in chlamydia and syphilis (~2/3)
 DoxyPEP Study
Design:
• Similar to IPERGAY trial
• Maximize data on adverse-event profile, adherence and antimicrobial resistance
• Evaluate net effectiveness of the intervention

Location:
San Francisco, Seattle

Intervention:
DoxyPEP vs. Standard of care (SOC)

Population:
• MSM and TGW taking HIV PrEP or living with HIV
 DoxyPEP Study
Design Inclusion criteria:
Randomized, open-label trial • Male sex at birth
N= 501 • At least 18 yrears old
MSM & TGW w/HIV (n= 174) • With HIV or on PrEP
MSM & TGW on HIV/PrEP (n= 327) • ≥ 1 STI in past 12 months
• Condomless sex with ≥ 1 male
Objective: partner in past 12 months
To assess the effectiveness, safety,
acceptability, and effect on antimicrobial STI testing: quarterly 3 site GC/CT
resistance of doxy-PEP in MSM and testing + RPR, GC culture before
transgender women taking HIV PrEP or living treatment
with HIV infection for the prevention of
bacterial STIs Exclusion criteria:
• Tetracycline allergy
• Taking medications with drug
Of 501 participants (327 in the PrEP cohort
interactions with doxycycline
and 174 in the PLWH cohort), 67% were
• Planning to take doxycycline for an
White, 7% Black, 11% Asian or Pacific
extended period
Islander, and 30% Hispanic or Latino.
 DoxyPEP Study

Primary Endpoint: STI Incidence Per Risk Reduction in STI

Incidence/quarter (95% CI)
Quarter
Percent of Quarterly Visits with an STI

35 PREP 66% (54% to

82/257 (31.9%) 76%)
39/128 (30.5%)
30
PLWH 62% (40% to
25 76%)
20 Total 65% (54% to
73%)
15
36/305 (11.8%)
61/570 (10.7%)
10

0
PrEP Cohort PLWH Cohort
Doxycycline PEP Standard of care

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted
Infections. N Engl J Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
 DoxyPEP Study
Individual STI Endpoints
25
Percent of Quarterly Visits with an STI 20.3%
20.2 %
20

14.8%
15
12.1%

10 9.1% 8.9%

5 3.9% 4.5%
2.7%
1.4%
0.4% 0.7%
0
PrEP - DoxyPEP PrEP - SOC PLWH - DoxyPEP PLWH - SOC

Syphillis Chlamydia Gonorrhea

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J
Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
 DoxyPEP Study: Effectiveness Against STI
Incidence

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J
Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
DoxyPEP Study : Effectiveness Against STI Incidence

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J
Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
 DoxyPEP Study : Effectiveness Against Incident STI
N. gonorrhoeae
Resistance observed at baseline:
• 4/15 N. gonorrhoeae isolates (27%)
Resistance observed after enrollment
• 5/13 isolates (38%) in doxy-PEP
groups
• 2/16 (12%) in SOC groups

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to

Prevent Bacterial Sexually Transmitted Infections. N Engl J Med.
 DoxyPEP Study : Effectiveness Against Incident STI
S. aureus
Resistance observed at baseline:
• 12% of isolates resistant to
doxycycline
Resistance observed at month 12
• 16% in doxy-PEP groups
• 8% in SOC groups

Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to

Prevent Bacterial Sexually Transmitted Infections. N Engl J Med.
2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
 DoxyPEP Study
Sexual Behavior and Adherence

Sexual Behavior Adherence to Doxy-PEP

Get vaccinated • 86% reported Doxy-PEP always/often
Earth is the third planet
Median of 9 sexual parternes within 72hrs after condomless anal or
from the Sun and(iQRthe only
4 to 7) with median of 5 sexual acts per vaginal sex
one with life
month (IQR 1.7 to 10.7) and 90.1% of sex as • 71% reported never missing doxycycline
comdomless. No change among significant after condomless sex
1 behavior at follow up. • Median Doxy-PEP doses: 4.0
doses/month (IQR: 1.0 to 10.0)
 DoxyPEP Study
Safety, Adverse Events, Acceptability

Safety and Acceptability

Adverse Events

One laboratory Acceptability

Adverse Events Adverse Events
abnormality
Two headaches/ 89% reported doxy-PEP was acceptable or very
Elevated liver Three diarrheal migraines acceptable
enzymes
 DoxyPEP Study

Conclusion:
• Doxy-PEP taken within 72 hours after condomless sex decreases incident
gonorrhea, chlamydia and early syphilis by 2/3 among MSM and TGW who
had a bacterial STI in the past year
• Doxy-PEP substantially reduced incidence of each STI, including gonorrhea,
among PrEP and PLWH cohorts
• Compared to IPERGAY trial, doxycycline showed approximately 55%
reduction in incident gonorrhea
 Hypothesis: Higher exposure to doxycycline may have improved effectiveness against
gonorrhea
• Doxy-PEP effectiveness against chlamydia was 88% in PrEP cohort and 74%
in PLWH cohort
• Incident diagnosis of syphilis was low, reduction in incidence still observed
more in Doxy-PEP group compared to SOC
 Why Doxycycline for PEP?

Prevented each
bacterial STI, High adherence and
including acceptability
gonorrhea

Acceptibilit
Efficacy
y

Safety Cost

Safe and well

Inexpensive
tolerated
Georgia Department of Health Recommendations for Doxy-
for
PEP
Gonorrhea, chlamydia, syphillis

Population:
• TGW
• Gay, bisexual, or other MSM
• People who have had at least one of these STIs in the past 12 months

Treatment:
• 2 tablets, or 200 mg, of Doxycycline
• 1 time, or no more than one dose per day
• Ideally within 24 hours, but no later than 72 hours after condomless sex
• The Georgia DPH recommends not exceeding 6 pills per week.

[8] UPDATE: Sexually transmitted infections - piedmont healthcare. Accessed September 29, 2023. https://www.piedmont.org/media/file/CME-PCP-
STI-Update.pdf.
 GOGO Vax Study

Double blinded
RCT Follow-up
Evaluating the efficacy of
4CMenB (Bexsero) in All subjects will be followed
preventing GC infection for 24 months

Two Interventions Pending Results

• 2 doses of Bexero at 0 and • Participants enrolled
3 months 11/2021 to 4/2023
• 2 doses of placebo • Results available 2025
(0.5 mL NS)
 ANRS DOxyVAC Study

Open-Label RCT Randomization

Aimed to prevent STIs in Arm 1: Doxycycline and Bexsero
MSM on PrEP Arm 2: Doxycyline and no Bexsero
Arm 3: No doxycycline and Bexsero
Arm 4: No doxycycline and no bexsero

Two Interventions
• PEP with doxycycline and
Preliminary
Bexsero vaccine Results
• Meningococcal B vaccine • No interaction between
(Bexsero) or no vaccine doxycyline and Bexsero
• 27% PEP vs. 73% no PEP
patients infected
Summary

2 of 3 high powered studies have shown

Doxy-
1 PEP
significant reductions of GC among MSM
3/3 shown significant reductions of
Chlamydia and Syphillis among MSM

Bexser Bexsero vaccine redced the incidence of

2 o
a first episode of GC among MSM

The efficacy data support doxy-PEP as

So a viable STI prevention strategy for
3 what? MSM with recent STIs and ongoing
condomless intercourse, independent of
HIV serostatus.
 References
[1] Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial
Sexually Transmitted Infections. N Engl J Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934

[2] Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually
transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS
IPERGAY trial. Lancet Infect Dis. 2018;18(3):308-317. doi:10.1016/S1473-3099(17)30725-9

[3] Incidence, prevalence, and cost of sexually transmitted infections in the united states | fact sheets |
newsroom | nchhstp | cdc.

[4] Sexually transmitted infections (Stis). Available from: https://www.who.int/health-topics/sexually-

transmitted-infections#tab=tab_1

[5] Figures [Internet]. www.cdc.gov.2023. Available from: https://www.cdc.gov/std/statistics/2021/figures.htm

[6] Home page for MMWR. Centers for Disease Control and Prevention. September 28, 2023. Accessed
October 5, 2023. https://www.cdc.gov/mmwr/index.html.

[7] Molina J-M et al. ANRS 174 DOXYVAC: an open-label randomized trial to prevent STIs in MSM on PrEP.
Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 119, 2023.

[8] UPDATE: Sexually transmitted infections - piedmont healthcare. Accessed September 29, 2023.
https://www.piedmont.org/media/file/CME-PCP-STI-Update.pdf. .
THANKS!
Do you have any questions?

[email protected]

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