Let's Talk about PrEP and DoxyPEP:

Prophylaxis of HIV and Other Sexually

Transmitted Infections
Ethan Robinson, PharmD
PGY1 Resident
January 18, 2024
Disclosures:
I have no relevant financial conflicts or other
conflicts of interest to disclose.
Abbreviations Used:
• aRRR: adjusted relative risk reduction • INSTI: integrase strand transfer inhibitor
• CAB: cabotegravir • IRR: incidence rate ratio
• MSM: men who have sex with men
• cis: cisgender
• NG: neisseria gonorrheae
• CrCl: creatinine clearance • NRTI: nucleoside reverse transcriptase inhibitor
• CT: chlamydia trachomatis • PEP: post-exposure prophylaxis
• DM: diabetes mellitus • PLWH: persons living with HIV
• PrEP: pre-exposure prophylaxis
• FTC: emtricitabine
• RR: relative risk
• HBV: hepatitis B virus • STI: sexually transmitted infection
• HCV: hepatitis C virus • TAF: tenofovir alafenamide
• TDF: tenofovir disoproxil fumarate
• HIV: human immunodeficiency virus
• trans: transgender
• HR: hazard ratio
• HSV: herpes simplex virus
 Discuss the epidemiology of HIV and bacterial
STIs in the United States and Indiana

Identify CDC guideline recommendations

for HIV pre-exposure prophylaxis and
Learning bacterial STI post-exposure prophylaxis.

Objectives Compare and contrast pharmacologic

options for HIV pre-exposure prophylaxis
based on clinical trials

Evaluate the safety and efficacy of post-

exposure doxycycline to prevent bacterial STIs
Epidemiology
Epidemiology of HIV
U.S. (2021) Indiana (2021)

About 1.1 million people living 12,347 people living with HIV
with HIV

36,126 new infections 528 new infections

AIDSVu. Local Data: United States. 2021. AIDSVu. Local Data: Indiana. 2021.
Epidemiology of HIV
U.S. (2021) Indiana (2021)

86% of new infections in males 80% of new infections in males

Male-to-male sexual contact

Black males are most affected with a

rate of 6x that of white males.

AIDSVu. Local Data: United States. 2021. AIDSVu. Local Data: Indiana. 2021.
PrEP Use in U.S. (2022)

PrEP to
435,677
92% male Need Ratio
users in
64% white (PNR) is
2022
12.06

Only 30% of people who could benefit are prescribed PrEP!

AIDSVu. Local Data: United States. 2021.

PrEP Use in Indiana (2022)

PrEP to
5,517 users 92% male Need Ratio
in 2022 78% white (PNR) is
10.45

AIDSVu. Local Data: Indiana. 2021.

Epidemiology of Bacterial STIs: U.S. (2021)

Gonorrhea: 710,151 cases

Chlamydia: 1.64 million cases

Syphilis: 176,713 cases

Centers for Disease Control and Prevention. National Overview of STDs, 2021. 2023.
Epidemiology of Bacterial STIs: Indiana (2021)

Gonorrhea: 14,486 cases

Chlamydia: 34,749 cases

Syphilis: 1,962 cases

Indiana Department of Health. Sexually Transmitted Infection (STI) Prevention. 2021.

Guideline Recommendations
Oral and Injectable PrEP Options
PrEP Option Clinical Pearls
• May be used for adults/adolescents ≥35 kg
• Not recommended if CrCl <60 mL/min
Truvada (emtricitabine/tenofovir
• 7 days for adequate rectal/penile and 21 days for vaginal concentrations
disoproxil fumarate)
• Safe in pregnancy
• Do NOT stop abruptly if HBV positive
• For use ONLY in adults/adolescents assigned male at birth ≥35 kg
Descovy (emtricitabine/tenofovir • Not recommended if CrCl <30 mL/min
alafenamide) • Contraindicated for use with strong CYP3A4 inducers
• Do NOT stop abruptly if HBV positive
• May be used for adults/adolescents ≥35 kg
• Intramuscular injection 600 mg/3 mL weeks 0 and 4, then every 8 weeks
thereafter
Apretude (cabotegravir) • Cabotegravir "tail" lasts up to 18 months
• Optional 4-week oral lead-in
• Contraindicated for use with certain anticonvulsants and rifampin due to
UGT1A1 metabolism

Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention
of HIV infection in the United States—2021 Update: a clinical practice guideline.
CDC: HIV Pre-exposure Prophylaxis Guideline
2021 Update Recommendations
IA IIA/B IIIB

Truvada or Apretude are Descovy is recommended

recommended as PrEP as a daily oral PrEP option All sexually active men and
options for adults and for trans women reporting women should receive
adolescents reporting risky risky sexual behaviors. information about PrEP.
sexual behaviors.

Clinicians should
Descovy is NOT
provide patients on
recommend for HIV
PrEP with access to
prevention through medication adherence
receptive vaginal sex. support.

Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the
prevention of HIV infection in the United States—2021 Update: a clinical practice guideline.
Monitoring Recommendations
HIV Testing STI Testing CrCl
Must test negative Test for NG, CT, and
within one week of syphilis every 3 months
for MSM and trans Every 12 months
starting PrEP
women

Test every 3 months Test for NG and syphilis

while on every 6 months for Every 6 months for
Truvada/Descovy heterosexual men and patients ≥50 years
women

Test every 4 Test for CT every 12

months while on months for
Apretude heterosexual men and
women

Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for
the prevention of HIV infection in the United States—2021 Update: a clinical practice guideline.
DoxyPEP
• CDC Guidelines for doxycycline post-exposure prophylaxis of
bacterial STIs are currently in development.
• A pre-recorded presentation is available summarizing available
studies.
• Current guidance is 200 mg of doxycycline (any formulation) to
be taken within 24 to 72 hours after condomless sex and no
more than 200 mg in 24 hours.

Centers for Disease Control and Prevention: Guidelines for the Use of Doxycycline Post-Exposure Prophylaxis for
Bacterial Sexually Transmitted Infection (STI) Prevention; Request for Comment and Informational Presentation.
Knowledge Check
Which of the following PrEP options would be
appropriate for a transgender woman with a CrCl of
40 mL/min?
A. Descovy

B. Truvada

C. Apretude

D. A and C

E. B and C
Which STI is NOT preventable with post-
exposure doxycycline?
A. Gonorrhea

B. Syphilis

C. Trichomoniasis

D. Chlamydia
Literature Review
iPrEx Trial

Multinational, Phase III, double-blind, randomized, placebo-controlled trial

1:1 randomization to receive FTC/TDF vs placebo

Primary Outcome: Incidence of HIV-1 infection

Secondary Outcomes: Adverse Effects

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Patient Population
INCLUSION Criteria EXCLUSION Criteria
• >18 years of age • Does not meet inclusion criteria
• Assigned male sex at birth
• HIV-seronegative
• High risk for acquiring HIV

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Patient Baseline Characteristics
FTC/TDF (n = 1251) Placebo (n = 1248)
Age (mean) 27.5 years 26.8 years

White 18% 17%

Black 9% 8%

Mixed Race 68% 70%

Asian 5.0% 5%

Hispanic 72% 73%

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Patient Risk Factors
FTC/TDF (n = 1251) Placebo (n = 1248)
Unprotected intercourse
with partner of
unknown/positive HIV 79% 81%
status in the past 6
months
Known partner with HIV
1.8% 2.6%
in the past 6 months
Transactional sex in the
41% 41%
past 6 months
Syphilis seroreactivity 13% 13%

Serum HSV-2 37% 35%

Current infection with
0.56% 0.48%
Hepatitis B

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Outcomes
• Primary Outcome: Incidence of HIV-1 Infection

• Intention to Treat: HR 0.53; 95% CI (0.36-0.78), p = 0.001

• Modified Intention to Treat: HR 0.56; 95% CI (0.37-0.85), p =

0.005

• Subjects with detectable FTC/TDF drug levels aRRR 95%; 95%

CI (70-99), p<0.001

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Outcomes
• Secondary Outcomes: Adverse Effects

• Serum Creatinine Elevation: 2.0% FTC/TDF vs 1.1% Placebo, p =

0.08

• Nausea: 1.6% FTC/TDF vs 0.72% Placebo, p = 0.04

• Unintentional Weight Loss of ≥5%: 2.2% FTC/TDF vs 1.1%

Placebo, p = 0.04

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

iPrEx Limitations

Lower than Lower than

expected expected FTC/TDF
adherence drug levels

Decreased high-
risk behavior

Grant RM, et al. N Engl J Med. 2010 Dec 30;363(27):2587-99.

IPERGAY Study

Multicenter, Phase III, double-blind, randomized, placebo-controlled trial

1:1 randomization to receive on-demand FTC/TDF vs placebo

Primary Outcome: Incidence of HIV-1 infection

Secondary Outcomes: Safety and adherence

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

IPERGAY Patient Population
INCLUSION EXCLUSION
• >18 years of age • HBV positive
• MSM and transgender women • Chronic HCV infection
who had unprotected sex with
• CrCl <60 mL/min (Cockcroft-Gault)
≥2 partners in the last 6 mo
• HIV-seronegative • ALT >2.5x ULN
• Glycosuria or proteinuria >1+ on
urine dipstick test

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

IPERGAY Baseline Characteristics
FTC/TDF (n = 199) Placebo (n = 201)
Age (median) 35 years 34 years

White 94% 89%

Serodiscordant
9.5% 6.5%
Partner
# of partners (median,
8 8
past 2 mo)
Circumcised 19% 20%

STI at baseline 25% 31%

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

IPERGAY Outcomes
• Primary Outcome: Incidence of HIV-1 infection

• The intention to treat analysis showed an 82% (95%

CI, 36-97; P=0.002) relative risk reduction

• The 2 participants in the treatment group who were

diagnosed with HIV were found to be non-adherent.

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

IPERGAY Outcomes
• Secondary Outcomes: Safety and adherence

• GI Upset (14% vs 5%), p = 0.002

Adverse • Elevated serum creatinine (18% vs 10%), p = 0.03
Events

• The median number of pills taken per month was 15 in both groups.
• Computer-assisted self reports show that on-demand PrEP was only used correctly 43%
Adherence of the time.

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

IPERGAY Limitations

Higher pill usage Self-

per month reported adherence

Majority white
population

Molina JM, et al. N Engl J Med. 2015 Dec 3;373(23):2237-46.

DISCOVER Study
Multicenter, Phase III, double-blind, randomized, active-controlled, non-
inferiority trial

1:1 randomization to receive FTC + TAF vs FTC + TDF

Primary Outcome: Incident HIV-1 Infection

Secondary Outcomes: Bone mineral density and renal biomarker safety

endpoints

Mayer KH, et al. Lancet. 2020 Jul 25;396(10246):239-254.

DISCOVER Patient Population
INCLUSION EXCLUSION
• >18 years of age • Does not meet inclusion criteria.
• MSM and transgender women
• High risk of HIV based on
sexual behavior or a history of
bacterial STIs in the past 24
weeks

Mayer KH, et al. Lancet. 2020 Jul 25;396(10246):239-254.

DISCOVER Baseline Characteristics
FTC/TAF (n = 2694) FTC/TDF (n = 2693)
Age (median) 34 years 34 years

White 84% 84%

Black 9% 9%

Asian 4% 4%

Other 3% 3%

Hispanic 24% 25%

Cisgender 98% 99%

Transgender 2% 1%
Taking FTC/TDF for
17% 16%
PrEP at baseline
Mayer KH, et al. Lancet. 2020 Jul 25;396(10246):239-254.
DISCOVER Outcomes
• Primary Outcome: Incident HIV-1 infection

• FTC/TAF was found to be non-inferior to FTC/TDF. IRR 0.47; 95% CI (0.19-1.15). The non-
inferiority margin was 1.62

• Secondary Outcomes: Bone mineral density and renal biomarker safety endpoints

• FTC/TAF was statisically superior to FTC/TDF for all six bone density and renal biomarker
endpoints after 48 weeks due to 90% lower tenofovir plasma concentrations.

Mayer KH, et al. Lancet. 2020 Jul 25;396(10246):239-254.

DISCOVER Limitations

Low HIV incidence Small transgender

reduced power population

No blood draws at
baseline

Mayer KH, et al. Lancet. 2020 Jul 25;396(10246):239-254.

DoxyPEP Study
Open-label, randomized controlled trial

2:1 randomization to receive 200 mg doxycycline vs standard care

Primary Outcome: Incidence of at least one STI per follow-up quarter

Secondary Outcomes: Incidence of each individual STI; safety, adverse

events and acceptability of doxycycline PEP

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

DoxyPep Patient Population
INCLUSION EXCLUSION
• >18 years of age • Tetracycline allergy
• MSM and transgender women • Concomitant medications with
• Taking PrEP or HIV-positive (2 interactions to doxycycline
separate cohorts) • Receiving extended treatment with
• Diagnosis of gonorrhea, doxycycline
chlamydia or syphilis in the
past year

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

DoxyPEP Baseline Characteristics
PrEP cohort PLWH Cohort
Doxycycline (n = Standard of Care (n Standard of Care (n =
Doxycycline (n = 119)
220) = 107) 55)

Age (median) 36 years 36 years 43 years 42 years

White 65% 63% 64% 70%

Black 4% 5% 13% 13%

Asian 16% 12% 6% 2%
Mixed Race 11% 20% 17% 15%

Hispanic 25% 38% 34% 25%

Cisgender 96% 100% 92% 98%

Gender
4% 0% 8% 2%
Diverse
Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.
DoxyPEP Patient Risk Factors
PrEP cohort PLWH Cohort
Standard of Care (n = Standard of Care (n =
Doxycycline (n = 220) Doxycycline (n = 119)
107) 55)
Any STI at
30% 25% 30% 36%
baseline
Gonorrhea
70% 73% 60% 71%
(past 12 mo)
Chlamydia (past
65% 59% 49% 49%
12 mo)
Syphilis (past 12
15% 1% 29% 31%
mo)
2 or more STIs
48% 41% 33% 47%
(past 12 mo)
# of partners
(median, past 3 8 10 7 10.5
mo)
Transactional
25% 38% 34% 25%
sex
Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.
DoxyPEP Outcomes
• Primary Outcome: Incidence of at least one STI per follow-up quarter

• PrEP Cohort: 10.7% vs 31.9%; RR 0.34; 95% CI (0.24-0.46), p<0.001

• PLWH Cohort: 11.8% vs 30.5%; RR 0.38; 95% CI (0.24-0.6), p<0.001

• PrEP Cohort: NNT to prevent a quarter with an STI incident is 5.

• PLWH Cohort: NNT is 6.

• 71% of participants reported never missing a dose of doxycycline.

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

DoxyPEP Outcomes
• Secondary Outcome: Incidence of each individual STI per quarter

• PrEP Cohort: 9.1% vs 20.2%; RR 0.45; 95% CI (0.32-0.65)

NG • PLWH Cohort: 8.9% vs 20.3%; RR 0.43; 95% CI (0.26-0.71)

• PrEP Cohort: 1.4% vs 12.1%; RR 0.12; 95% CI (0.05-0.25)

CT • PLWH Cohort: 3.9% vs 14.8%; RR 0.26; 95% CI (0.12-0.57)

• PrEP Cohort: 0.4% vs 2.7%; RR 0.13; 95% CI (0.03-0.59)

Syphilis • PLWH Cohort: 0.7% vs 2.3%; RR 0.23; 95% CI (0.04-1.29)

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

DoxyPEP Outcomes
• Additional Outcomes: Safety, adverse events and acceptability of doxycycline
PEP

• Adverse Events: Transaminitis (n = 1, Grade 2), Diarrhea (n = 3, Grade 3),

Headache/Migraine (n =2, Grade 3)

• 2% of patients discontinued doxyPEP based on preference or adverse events.

• 89% of patients reported taking doxyPEP as accetable or very acceptable.

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

DoxyPEP Limitations
Patient- Small
reported transgender
adherence population

Varying
tetracycline
resistance

Luetkemeyer AF, et al. P N Engl J Med. 2023 Apr 6;388(14):1296-1306.

Patient Case
• A 36 yo cisgender, homosexual male with a PMH of DM and migraines reports having
condomless sex on average with three to five partners per month of unknown HIV status.
He has been diagnosed and treated for both gonorrhea and chlamydia in the past year
and is interested in STI prevention. He is immune to Hep A & B and is currently HIV
negative. His estimated CrCl is 84 mL/min. His last A1C was 6.4%. He has NKDA and
currently takes metformin 1000 mg BID, Ozempic 1 mg weekly, topiramate 50 mg BID,
and melatonin 10 mg qHS.
• Which of the following options is best for this patient?
A. Initiate Descovy 200/25 mg 2 tabs Day 1, then 1 tab daily (days 2-3) PRN
B. Initiate Truvada 200/300 mg once daily and doxycycline 100 mg BID
C. Initiate Truvada 200/300 mg once daily and doxycycline 200 mg once daily PRN
Summary
 A large number (70%) of patients who could benefit from
PrEP are not on it, and minority groups (particularly black
people and transgender women) continue to have a
disproportionate incidence of HIV.

Personal Recent clinical trials demonstrate the astounding efficacy

and safety profiles of various PrEP options including

Conclusions Truvada, Descovy, and Apretude at preventing new HIV

infections.

DoxyPEP is a new safe and effective strategy at preventing

bacterial STIs in MSM and trans women. Phase IV data will be
essential to determining the true effect on STI incidence and
antibiotic resistance.

49
Let's Talk about PrEP and DoxyPEP:
Prophylaxis of HIV and Other Sexually
Transmitted Infections
Ethan Robinson, PharmD
PGY1 Resident
January 18, 2024
References
1. AIDSVu. Local Data: United States. 2021. https://aidsvu.org/local-data/united-states/
2. AIDSVu. Local Data: Indiana. 2021. https://aidsvu.org/local-data/united-states/midwest/indiana/
3. Centers for Disease Control and Prevention. National Overview of STDs, 2021. 2023. https://www.cdc.gov/std/statistics/2021/overview.htm
4. Indiana Department of Health. Sexually Transmitted Infection (STI) Prevention. 2021. https://www.in.gov/health/hiv-std-viral-hepatitis/sexually-
transmitted-disease-prevention-program/
5. Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the
United States—2021 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf.
6. Centers for Disease Control and Prevention: Guidelines for the Use of Doxycycline Post-Exposure Prophylaxis for Bacterial Sexually Transmitted
Infection (STI) Prevention; Request for Comment and Informational Presentation. https://www.federalregister.gov/documents/2023/10/02/2023-
21725/guidelines-for-the-use-of-doxycycline-post-exposure-prophylaxis-for-bacterial-sexually-transmitted
7. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med.
2010 Dec 30;363(27):2587-99. doi: 10.1056/NEJMoa1011205.
8. Mayer KH, Molina JM, Thompson MA, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for
HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-
inferiority trial. Lancet. 2020 Jul 25;396(10246):239-254. doi: 10.1016/S0140-6736(20)31065-5.
9. Molina JM, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015 Dec
3;373(23):2237-46. doi: 10.1056/NEJMoa1506273.
10. Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J
Med. 2023 Apr 6;388(14):1296-1306. doi: 10.1056/NEJMoa2211934.