Common Non-Viral Stis, EPT

Common Non-Viral STIs, EPT, and PrEP: Highlights and Updates Angela Kuznia MD, MPH - Clinical Assistant Professor Department of Family Medicine - University of Michigan Medical School 56th Annual Northern Michigan Family Medicine Update June 24, 2021 DISCLOSURES

• I have no relevant conflicts of interest to disclose. ACKNOWLEDGEMENT

• This presentation was researched and prepared in conjunction with an Adolescent Medicine Fellow from the University of Michigan Department of Pediatrics.

• Thank you to Dr. Bernie Stoody! OBJECTIVES

• Describe the disproportionate burden of disease among adolescents and sexual and racial minority groups. • Identify signs and symptoms of common non-viral sexually transmitted infections (STIs). • Identify indications for screening and interpret diagnostic test results related to common non-viral STIs. • Formulate management plans, including expedited partner therapy (EPT), for common non-viral STIs. • Identify indications for pre-exposure HIV prophylaxis (PrEP), conduct medication surveillance, and apply strategies to optimize adherence. DEMOGRAPHICS & RISKS

Vulnerabilities of adolescents & young adults (AYAs): • Impulsivity, reward-seeking, high risk behaviors • Fear, confidentiality, logistics of accessing clinical care • Cervical ectopy

https://www.cdc.gov/std/statistics/prevalence-incidence-cost-2020.htm DEMOGRAPHICS & RISKS

Among high-school students: • 38% have undergone sexual debut • 27% sexually active currently (2009:34%) • 21% used substances before last sexual intercourse • 9% have had > 4 sexual partners (2009:14%) • 54% condom at last sexual intercourse (2009: 62%)

Qu Y, et al 2015l Newon-Levinson, et al 2016; McKee, et al 2006; National Youth Risk Behavior Surveys 1991-2019; DEMOGRAPHICS & RISKS

• Chlamydia (CT) and Gonorrhea (GC) • 2018-2019: increased # cases overall • Highest risk: men who have sex with men (MSM) • GC 42x higher among MSM than men who have sex with women only (MSW) • Trichomoniasis • Disproportionately high disease burden in: • Black females • Older adolescents; especially incarcerated AYAs • Syphilis (25% of cases among 15-24yo) • Disproportionately high disease burden in: • Southeastern states • Black individuals • Males (2019: 56.7% of cases were among MSM) LOCATION, LOCATION, LOCATION

Limited access to care = 2019: 30.6% of all cases of Chlamydia, Gonorrhea, and primary and secondary syphilis were among non-Hispanic Black people (i.e. among 12.5% of the US population). Q #1 Q #1

Which of the following is recommended regarding follow-up chlamydia testing for a woman treated for uncomplicated cervical chlamydia who does not have persistent or recurrent symptoms? a) Perform a test-of-cure nucleic acid amplification test (NAAT) 10 days after treatment completion b) Perform a test-of-cure nucleic acid amplification test (NAAT) 2 months After treatment completion c) Send a cervical specimen for culture and sensitivity testing within 2 weeks of the positive nucleic acid amplification test (NAAT) result d) Screen for re-infection 3 months after completion of therapy Q #1

• Mostly asymptomatic (75% of females and 50% of males) • Females • Cervicitis + discharge • Urethral involvement: dysuria and frequency • Nonspecific: irregular bleeding, pelvic discomfort • Males • Urethritis • Epididymitis • +/- discharge CHLAMYDIA – SIGNS & SYMPTOMS

• Untreated infection in females • Pelvic inflammatory disease (PID) with possible perihepatitis • Ectopic pregnancy • Infertility

• Both sexes could present with conjunctivitis (autoinoculation), severe pharyngitis, proctitis or proctocolitis, or reactive arthritis Q #2 Q #2

A 19-year-old MSM visits your clinic for HIV testing and STI screening. In the past 6 months, he has had 4 different male partners and practices insertive and receptive anal and oral sex. He intermittently uses condoms. Overall, his health is good and he currently has no genitourinary or pharyngeal symptoms.

Which of the following is the most appropriate approach to screen this patient for chlamydia and gonorrhea? a) Screen at anal and oropharyngeal sites at least every 6 months b) Screen at urethral, anal, and oropharyngeal sites at least annually c) Screen at urethral and anal sites at least every 12 months d) Routine screening for chlamydia infection is not recommended Q #2

• Annual screening of all sexually active women <25 y/o • Should be considered for men if: • Presenting to a clinic with high prevalence of STIs • MSM • New partner or partner with STI • Screen transgender patients according to age, sexual activity, and current anatomy CT & GC – SCREENING PEARLS

• Urine NAAT is at least as sensitive as clinician/self-collected vaginal and urethral specimens in clinic settings.

• Consider adding screening for trichomonas in high risk individuals (i.e., history of STI, multiple sex partners, adolescents)

• In females 15-24yo, consider a UNIVERSAL APPROACH that does not rely on endorsement of sexual activity CT & GC – DIAGNOSTIC TESTING

NAAT: gold standard • first catch urine, vaginal, oropharyngeal, or rectal swabs

If test positive, offer HIV testing • CT infection increases risk of HIV infection 5-fold CHLAMYDIA – TREATMENT

1st line: Azithromycin 1 g PO once or doxycycline 100 mg PO BID x7d, w/ abstinence for 7d upon completion of rx • Alternative Regimens: - Erythromycin 500 mg PO QID x7d - Levofloxacin 500 mg PO daily x7d - Ofloxacin 300mg PO BID x7d • Test again in 3 mo to assess for repeat infection • If pregnant: avoid doxy, re-test 3-4wk after therapy completed GONORRHEA – SIGNS & SYMPTOMS

Men • ~50% are symptomatic • Urethritis: mucopurulent or purulent urethral discharge and dysuria • Proctitis: including anal bleeding, itching, irritation, painful defecation, painless/purulent discharge • Epididymitis • Prostatitis • Perirectal or periurethral abscess GONORRHEA – SIGNS & SYMPTOMS

Women • often asymptomatic (80%) • Cervicitis or urethritis • Accessory gland infection (e.g. Skene or Bartholin glands) • PID • Perihepatitis Q #3 Q #3

You diagnose an18-year-old patient with cervical gonorrhea. She has no symptoms, and co-testing for chlamydia is negative. Her weight is 143lb. Based on the 2020 updated recommendations from the Centers for Disease Control (CDC), what regimen should be used to treat this patient’s cervical Neisseria gonorrhoeae infection? a) Ceftriaxone 250 mg IM in a single dose b) Ceftriaxone 500 mg IM in a single dose c) Ciprofloxacin 500 mg PO as a single dose plus doxycycline 100 mg PO BID x7 days c) Cefixime 400 mg PO daily x7 days plus azithromycin 1g PO in a single dose Q #3

Uncomplicated cervical, urethral, rectal, pharyngeal, or conjunctivitis infections: • Ceftriaxone 500 mg IM once (1G if >300lb) • 2nd line: oral cefixime 800 mg • Pharyngeal or conjunctivitis -- must obtain test of cure 14 days after rx • combination therapy with 2 antimicrobial drugs is recommended only when chlamydia infection has not been excluded • First-line co-infection tx is now doxycycline 100 mg BID x7d • Repeat testing in 3 mo due to high rate of reinfection (not test of cure) EPT – CT & GC

• Who is eligible: • Any partners within 60 days preceding symptom onset or diagnosis • most recent partner if >60 days

• Should be deferred if: • Female partner experiencing symptoms of PID • MSM, due to high risk of co-infection w/ syphilis or HIV, lack of efficacy data, and increasing resistance to cefixime (GC) in this population

• Requires abstinence until 7 days post treatment and resolution of all symptoms EPT PEARLS

• Screen for intimate partner violence, human trafficking • Provide resources regarding medication and anticipatory guidance for seeking medical evaluation (e.g. signs and symptoms of anaphylaxis) • Encourage communication regarding importance of seeking medical care for additional screening • Highlight the high occurrence of re-infection. Q #4 Q #4

A 17-year-old female presents with prolonged menstrual bleeding associated with severe menstrual cramping. She experienced menarche at 13 y/o and has always experienced monthly menstrual cycles, of ~5 days duration, with average flow associated with mild menstrual cramping, responsive to Motrin. This current cycle began ~1 month ago and is associated with severe abdominal pain. She is sexually active with one male partner and practices inconsistent condom use. On exam, she is febrile and uncomfortable with HR: 120 bpm. She does not appear anemic and capillary refill is <3 seconds. On abdominal exam, she is severely tender to palpation at the right upper and lower quadrants. Given the severity of her pain, she defers a pelvic exam.

Which of the following is true regarding her most likely etiology to her current clinical presentation? a) She has a 5% chance of infertility if she experiences this condition 3 times. b) This condition increases the risk of ectopic pregnancy 6 fold. c) After obtaining a urine sample, treatment should be deferred until confirmatory results are available. d) A test of cure should be obtained in 2-6 months after treatment. PELVIC INFLAMMATORY DISEASE (PID) – PATHOGENESIS • A clinical syndrome of non-specific signs and symptoms that results from the ascension of microorganisms from the cervix and vagina to the upper genital tract • Most commonly caused by chlamydia and/or gonorrhea

• Broad differential diagnosis (GU + GI)

• Pregnancy (including ectopic pregnancy) must be excluded PELVIC INFLAMMATORY DISEASE (PID) – COMPLICATIONS

• Acute: salpingitis, tubo-ovarian abscess, perihepatitis

• Chronic: ectopic pregnancy, infertility, chronic pelvic pain • Chances of infertility are 8%, 20%, and 50% after 1st, 2nd, and 3rd episodes respectively • PID increases the risk of ectopic pregnancy 6-fold PELVIC INFLAMMATORY DISEASE (PID) – DIAGNOSIS & TREATMENT

• Initiate empiric treatment if abdominopelvic pain without an identifiable cause, in female at risk of STI and >1 of the following: • Uterine tenderness • Cervical motion tenderness • Adnexal tenderness

• Urgency: risk of infertility and ectopic pregnancy increases within 72 hours PELVIC INFLAMMATORY DISEASE (PID) – ADMISSION CRITERIA (IV ABX)

• Inability to confirm diagnosis and r/o surgical emergency • Tubo-ovarian abscess • Severe illness w/ systemic symptoms • Pregnancy • HIV infection • Failure to respond to outpatient oral rx w/in 48-72hr • PO intolerance PELVIC INFLAMMATORY DISEASE (PID) – OUTPATIENT TREATMENT • Outpatient • Broad coverage for CT and GC with anaerobic coverage • Ceftriaxone 250 mg IM + doxycycline 100 mg PO BID x14 days + metronidazole 500 mg PO BID x14 days

• Repeat screen in 2-6 months (test for re-infection)

• EPT • Treat as CT + GC using EPT guidelines Q #5 Q #5

A 16 y/o female presents to you with a “bad smell” and “itching down there”. She is experiencing daily discharge that leaves her underwear stained. No fever, abdominal pain, or dysuria. She completed a course of antibiotics for a sinus infection recently. She is sexually active with her 18 y/o boyfriend (vaginal) and reports inconsistent condom use. Physical exam reveals a well-appearing female with a benign abdominal exam, negative for suprapubic tenderness. You visualized this on speculum exam. Otherwise, pelvic exam is negative for cervical motion tenderness or adnexal tenderness. Which of the following is true regarding the etiology of her presentation? a) Treatment involves metronidazole 2 g PO once. EPT is indicated. b) Most female patients are symptomatic. c) A test of cure should be obtained in 3 mo following treatment. d) Treatment involves metronidazole 2 g PO once. EPT is not indicated. Q #5

• Females (80% asymptomatic) Profuse, yellowish-greenish, malodorous vaginal discharge, vulvar irritation; “strawberry cervix” on exam

• Males: urethritis, epididymitis, or prostatitis

• Testing: NAAT is gold standard - 3-5x more sensitive than wet mount TRICHOMONIASIS - TREATMENT

First Line: Metronidazole 2 g PO once (500mg BID x7d if not tolerated) • Alternative: Tinidazole 2 g PO once • Resistant/Recurrent Disease • Metronidazole 500 mg PO BID x7d or step-up to 2 g daily x7d • Tinidazole 2 g PO daily x7d (CI in pregnancy)

• Abstinence until both partners treated and asymptomatic for 7d • Abstinence from alcohol until 24hr after metronidazole and 72 hr after tinidazole • Repeat testing in 3 mo due to high re-infection rate EPT - TRICHOMONIASIS

• Current partner(s), same regimen as patient

• Abstinence until adequate partner treatment and symptom resolution

MI Law: Expanded legally permissibility includes trichomonas during COVID-19 public health crisis Q #6

A 20-year-old MSM presents with a 4-day history of painless penile lesions. He has had 2 partners in the last 6 months. Physical exam reveals 3 non-tender ulcers on the lateral aspect of the penile shaft and firm lymphadenopathy in the right inguinal region that is nontender. Oral examination and skin inspection are normal. He has no neurologic symptoms. Which of the following is true regarding the most likely etiology of his current presentation? a) The current stage of his infection warrants a 3 doses of IM benzathine penicillin G. EPT should be sent. b) The current stage of his infection warrants a single dose of IM benzathine penicillin G. EPT should not be sent but the partner should be encouraged to seek evaluation. c) Once treatment is complete, follow up serology is not indicated. d) Patients with this condition should undergo HIV and STI screening every 12 months. Q #6

Primary • appears after 9-90 day incubation period (avg: 21 days) • Ulcerating lesion in genital area, cervix, anus, lips/mouth, or elsewhere (eg skin of extremities or breasts) • Painless, “punched out lesion” - chancre • Could appear to be “kissing lesion” – adjacent ulcer across fold of skin • Typically heal w/in 3-6 weeks • Can be a/w bilateral LAD SYPHILIS – STAGES OF INFECTION

Secondary • 4-10 weeks after primary sx • Systemic signs: 90% • Maculopapular rash involving trunk, extremities, palms, soles • Condyloma lata: gray or white lesions at mucous membranes • Constitutional symptoms: LAD, malaise, myalgias SECONDARY SYPHILIS • Latent • Early: asymptomatic with a positive RPR within 1 year of symptom onset. Potentially infectious (recurrent signs/symptoms can go unnoticed). • Late: asymptomatic with a positive RPR > 1yr after symptom onset. Not infectious.

• Tertiary • Dementia, aortic aneurysms and regurgitation, granulomas (gummas) of the skin, bones, or internal organs SYPHILIS – STAGES OF DISEASE SYPHILIS - SCREENING

• Annual screening for: • MSM • HIV+ and sexually active

• Recent diagnosis in partner

• RPR/VDRL is first-line screen • Followed by FTA-abs if positive SYPHILIS – DIAGNOSTIC TESTING

• Treat immediately if high suspicion for primary or secondary syphilis

• Nontreponemal serologic testing (RPR) can be first-line screen, and test of response to rx • Confirmed with treponemal test (fluorescent treponemal antibody absorbed [FTA-ABS])

• If negative but clinical suspicion: repeat screen in 1 week, 1 mo, and 3 mo SYPHILIS - TREATMENT

Benzathine penicillin G • 1 dose for primary, secondary, or early latent • HIV-: Repeat RPR in 6-12 months • HIV+: Repeat RPR at 3,6,9,12, and 24 mo. • 3 doses (weekly x3) for late latent or tertiary syphilis • Jarisch-Herxheimer reaction w/in 2 hrs: fever, chills, myalgia, 12-24 hrs; responsive to aspirin and rest

• If PCN allergic (primary and secondary syphilis only): • PCN skin testing and desensitization recommended • Doxycycline 100mg BID x14d • Tetracycline 500mg QIDx14d • ? Ceftriaxone 1-2g IM/IV daily x10-14d PARTNER THERAPY - SYPHILIS

Not EPT-eligible! Treatment depends on syphilis presentation/stage of infected partner: • New diagnosis– treat even if serology is negative • If infected >90 days: treat if serology not immediately available and follow-up uncertain • If secondary syphilis and sexual activity within 6 months of symptom onset • If early latent syphilis and sexual activity within 1 year • If long-term partner with positive serology

• If asymptomatic, must be treated with 3 PCN doses (i.e. assume latent syphilis of unknown duration) Q #7 Q #7

She is an appropriate candidate for pre-expA 16-year-old presents to clinic for her annual HME. On HEADSS assessment she endorses sexual activity (vaginal) with 3 male partners over the past 6 months, with inconsistent condom use. She and her partners identify as polyamorous and she is aware of her partners having other sexual partners themselves. She is currently asymptomatic, not on any medications, and has no significant past medical history. On physical exam, weighs 140 lb. Which of the following is accurate regarding her preventative health care? a) She is an appropriate candidate for pre-exposure HIV prevention with emtricitabine 200 mg in combination with tenofovir alfenamide 25 mg (brand name Descovy) b) Adherence counseling should emphasize the requirement for daily medication intake for effective HIV prevention. c) To prevent a lapse in management, a 90-day supply of pre-exposure prophylaxis should be sent to the local pharmacy and must have 3 refills. d) Pre-exposure prophylaxis for HIV prevention is considered STI management and does not require parental consent for patients <18 years old. PrEP - INDICATIONS PrEP – PRE-INITIATION TESTING

• HIV Serum Ag/Ab • Renal function panel • Truvada should not be administered with eCrCl<60 mL/min • Descovy should not be administered with eCrCl<30 mL/min • Hepatitis serology (HBV and HCV) • GC/CT and syphilis screen PrEP – OPTIONS

• Truvada – 1 tablet daily • emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg • Descovy – 1 tablet daily • Not evaluated for use against HIV from receptive vaginal sex • emtricitabine 200 mg + tenofovir alafenamide 25 mg • FDA approved for persons > 35 kg • Maximum intracellular concentrations of activated tenofovir disoproxil fumarate: • Serum: 20 d • Rectal tissue: 7d • Cervicovaginal tissue: 20 d PrEP – SIDE EFFECTS & ADVERSE EFFECTS • Generally uncommon and resolve within first month of PrEP • Nausea, flatulence, rash, headache

• Review signs/symptoms of acute renal failure or acute HIV that would warrant urgent evaluation

• Decreased bone mineral density possible with tenofovir disoproxil fumarate PrEP – MEDICATION MONITORING

1 mo At least every 3 mo At least every 6 mo • Assess and confirm HIV- • Repeat HIV testing and • Monitor eCrCl negative status assess for acute infection • STI testing for sexually • Assess for early side effects • Repeat pregnancy testing active adolescents and • Address adherence issues • STI testing if sexually active adults (syphilis, GC, and CT) with signs/symptoms of regardless of signs and infection symptoms • STI testing if MSM with history of STI or multiple partners PrEP – CLINICIAN RESOURCES

• HIV Nexus CDC: https://www.cdc.gov/hiv/clinicians/index.html • National Clinicians Consultation Center PrEP Line @ 1-855-448- 7737 (M-F 9:00 AM – 8:00 PM EST) • Michigan PrEP Provider Toolkit: https://www.michigan.gov/documents/mdhhs/PrEP_Provider_Toolkit_ MDHHS_547647_7.pdf • MD at site • Title X clinic does not require parental consent for minor prescription PrEP – PATIENT RESOURCES

• Free PrEP: https://www.getyourprep.com • Co-pay assistance: https://www.gileadadvancingaccess.com/ • PrEP provider locator: https://preplocator.org • Includes options tailored to insurance status PrEP – ADHERENCE

Doses per week of Truvada HIV risk reduction efficacy

7 99% 4 96% 2 76%

• Significant protection against HIV infection with partial adherence depends on tissue • 6-7 doses per week for lower vaginal tract tissues • 2 doses per week for colorectal tissue PrEP - ADHERENCE CLINICIAN RESOURCES CLINICIAN RESOURCES TAKE-HOME POINTS

• There is a disproportionate burden of disease among populations based on age, sex, and race and ethnicity. • Non-viral STIs are often asymptomatic. Routine screening is associated with increased uptake. • Screening allows early detection and early intervention to avoid long-term consequences. • EPT is critical to avoiding reinfection. • PrEP is FDA-approved for use and is highly effective HIV-prevention among persons at high risk. References • National Academies of Sciences, Engineering, and Medicine 2021. Sexually Transmitted Infections: Adopting a Sexual Health Paradigm. Washington, DC: The National Academies Press. https://doi.org/10.17226/25955external icon

• St. Cyr S, Barbee L, Workowski KA, et al. Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911–1916. DOI: https://dx.doi.org/10.15585/mmwr.mm6950a6external icon

• Screening Recommendations and Considerations Referenced in Treatment Guidelines and Original Sources: https://www.cdc.gov/std/tg2015/screening-recommendations.htm

• Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines- 2017.pdf. Published March 2018.

• Centers for Disease Control and Prevention. Tracking the Hidden Epidemics: Trends in STDs in the United States, 2000. Atlanta, Ga.; Centers for Disease Control and Prevention; 2001:1-31.

• Farley TA, Cohen DA, Elkins W. Asymptomatic sexually transmitted diseases: the case for screening. Prev Med. 2003;36:502-509. • https://www.std.uw.edu • https://www.cdc.gov/std/tg2015/default.htm • https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021752s035lbl.pdf • https://www.gilead.com/~/media/Files/pdfs/medicines/hiv/descovy/descovy_pi.pdf