STD UpdateWAPA Winter Conference, 2013

Julie Dombrowski, MD, MPH

Assistant Professor, Medicine/Infectious Diseases

Medical Director, King County STD Clinic

Overview Cases highlighting key points Chlamydia and gonorrhea - gonorrhea resistance NGU Syphilis - testing algorithm Genital Herpes Vaginitis Miscellaneous key points Revisit cases

Case 1A 22 year-old woman comes to your clinic for “a check-up”. She is sexually active with her boyfriend and had one other male partner in the past year. She had a “negative STD screen” prior to starting her relationship with her boyfriend. She does not need a Pap test today.

Which is the most appropriate testing in this case?

A) Urine specimen for chlamydia and gonorrhea culture

B) Cervical swab for chlamydia and gonorrhea nucleic acid amplification test (NAAT)

C) Vaginal swab for chlamydia and gonorrhea NAAT

D) None of the above – she does not need STD screening

Case 2A 24 year-old man comes to see you for urethral discharge and burning with urination x 3 days. He has had 4 female sex partners in the past year. On exam, you find yellowish penile discharge. You do not have access to a microscope, but you plan to send a urine sample for gonorrhea and chlamydia NAAT.

How will you treat him?

A) No indication for treatment today – await lab results B) azithromycin 1gram po x 1 C) cefixime 400mg po x 1 + azithromycin 1gram po x 1 D) ceftriaxone 250mg IM + doxycycline 100mg po BID E) ceftriaxone 250mg IM + azithromycin 1 gram po

Case 3A 29 year-old new patient comes to see you about “sores on my penis”. On exam, you see:

A) Have you ever had this before? B) Do you have sex with men, women or both? C) Did you have tingling before you saw the sores? D) Are these painful?

What is the most important history question for diagnosis and appropriate treatment in this case?

Case 4You are seeing a 26 year-old woman for follow-up after her first prenatal visit (G0P1), at which she was screened for syphilis. She and her husband have been monogamous and married for 3 years. Her test results are:

T. pallidum EIA: POSITIVE Rapid plasma reagin (RPR): NEGATIVE T. pallidum particle agglutination assay (TPPA): NEGATIVE

What do you tell her? A) She has syphilis and needs treatment B) She has syphilis, she needs treatment, and her husband needs

testing and treatment C) She might have syphilis, she needs treatment, and her husband

needs testing and treatment D) She does not have syphilis. She has a false positive test result.

Case 5A 27 year-old woman who requested serologic screening for herpes has a positive HSV-2 antibody using a FOCUS EIA assay with a value of 3.8. She has no history of clinical herpes.

What do you tell her?

A) She very likely has genital herpes caused by HSV-2, and just never had a symptomatic outbreak

B) The HSV-2 antibody result is probably a false positive

C) She is probably actively seroconverting to HSV-2, having acquired it from her current partner

D) You need to check a Herpes IgM antibody to clarify the results

Chlamydia & Gonorrhea

Chlamydia—Rates by Sex, United States, 1991–2011

NOTE: As of January 2000, all 50 states and the District of Columbia have regulations that require the reporting of chlamydia cases.

2011-Fig 1. SR

Pelvic inflammatory disease — Initial visits to physicians’ offices by women 15 to 44 years of age:

United States, 1980–2010

SOURCE: National Disease and Therapeutic Index (IMS Health)

0

100

200

300

400

500

Chlamydia Incidence Rates Among Women By County Washington State, 2010

Washington State Department of Health

STD/TB Services

IDRH Assessment Unit

County Incidence Rates Per 100,000

Asotin

5

Rates not calculable

Clark469

Whatcom 422

Clallam371

Jefferson261

Grays

Harbor

321

*Wahkiakum

Cowlitz496

Mason346

Island334

San Juan

Skagit421

Snohomish

334

King407

Okanogan385

Chelan366 Douglas

317

Skamania299

Klickitat238

Benton531 Walla Walla

420

Pacific

237

Lewis332

Thurston

453

Pierce684

Kittitas324

Yakima825

Franklin726

Grant509 Adams

796

Lincoln*

Ferry

Stevens245

Pend

Oreille

188

Spokane524

Whitman421

Columbia*

Garfield*

Kits

ap

463

>500

Asotin

284

* Rates are not calculated from 0 to 4 cases because they are unreliable.

<300301-500

Chlamydia Incidence increasing Morbidity appears to be decreasing We need to:

Improve screening ~57% of eligible women in WA State screened annually

Improve partner treatment Expedited partner therapy

Improve rescreening Rescreen all persons diagnosed with chlamydia 3 months

after treatment

Major Clinical Syndromes Caused by C. trachomatis

Women

Urethra

Bartholin’s glands

Cervix

Rectum

Urethritis

abscess

Cervicitis

Proctitis

Ectopic pregnancy

Chronic pelvic pain

Infertility

Anatomic Site SequellaeSyndrome

Pelvic Inflammatory Disease

Most (80-90%) women infected with chlamydia have normal cervix / no signs

10-20%

~24,000 women per year

in the US

Randomized Trials of Chlamydial Screening

Author Population Design PID Incidence in Untested (per 100

person yrs)

RR

Scholes (1996)

♀ GHC

Prevalence 7%

RCT screening vs. no screening

2.2 0.44 (0.2-0.9)

Ostergaard (2000)

Danish high school students Prevalence 5%

RCT Screening vs. no screening via

mail

4.2 0.50 (0.23-1.1)

Oakshott* (2010)

♀ UK Students

Prevalence 5.4%

RCT screening vs. specimen collection

but not testing

1.9 0.65 (0.34-1.22)

* 83% reduction in PID among women who tested CT positive at baseline. 79% of PID cases occurred in women who tested negative for chlamydia at baseline

9.5% of women with CT at baseline who were untreated developed clinical PID within 1 year

CDC Guidelines 2010: CT & GC Screening for Women

Annual Chlamydia screening for all sexually active women age ≤ 25 Gonorrhea screening recommended also

Older than 25 – screen women at increased risk Multiple partners, drug use, commercial sex work, inconsistent

condom use, previous STDs

Other Criteria – IDU insertion, pregnancy Above applies to women who have sex with women

Nucleic Acid Amplification Testing (NAAT)

Culture: cultivates live organisms Not widely available for Chlamydia trachomatis

NAAT: detects genetic material (DNA or mRNA) More sensitive than culture for GC and CT at all

anatomic sites Vaginal swabs preferred specimen for screening

women, but urine and cervical also acceptable

Clinician-obtained Patient-obtained

Partner Notification & Treatment Sex partners from past 60 days should be evaluated,

tested, and treated Expedited partner therapy (EPT) for GC/CT

Increases likelihood that partners are treated and decreases Washington State DOH, 2004: “If treatment is not otherwise

assured, the patient should be provided antibiotics for their partner(s). These medications must include appropriate written information for the treated third party.”

Heterosexuals with GC or CT should be routinely offered medication for their sex partner if you are not confident that you can otherwise treat the partner(s)

PDPT Individual RCT

4

6

8

10

0 1 2 3 44

6

8

10

12

14

16

0 1 2 3 4

Chlamydia Positivity Gonorrhea Incidence

Per

cent

Cas

es/1

00,0

00

Time Time

Trends in Chlamydia Positivity Among Women Age 15-25 Tested Through IPP Clinics and Gonorrhea Incidence in WA State Women

P<.001 for both chlamydial positivity and gonorrhea incidence

Slide courtesy of Dr. Matthew Golden

Effect of EPT on Chlamydial Positivity and Gonorrhea Incidence in Women, Randomized Trial

ITT Analysis

Risk Ratio

95% CI

Chlamydial positivity in women

.89 .77-1.04

Gonorrhea incidence in women

.86 .69-1.08

* Analysis controls for secular trend that may have been ongoing independent of the study intervention

Slide courtesy of Dr. Matthew Golden

Case Reports - Washington State Department of Health (DOH) Home PageJul 30, 2010 ... Access Washington Logo linking to Access Washington. Notifiable Condition Case Report Forms for STD, by County. Click on the map to go to the Case Report ...www.doh.wa.gov/cfh/std/casereports/de... - Cached - Similar

Reporting a Case (WA example)

Step 1: Google “STD case report WA” and click on first link

Step 2: Click on your county on this map

Step 3: Fill out this form & fax to the number at the top of the page(partner instructions on back)

PDPT Packs in WA State

Information provided with EPT

Information about medications & STD

Advice about complications and need for care (e.g. PID)

Where to seek care

Recurrent Gonorrhea & Chlamydial Infection*

9.4

12.611.7

13.3

0

2

4

6

8

10

12

14

Gonorrhea Chlamydia

Men Women

Per

cen

t

* In absences of PDPT

Retesting: Test of cure vs. Rescreening

Test of cure for GC & CT? Not recommended, unless

Pregnancy

Persistent symptoms in patient or partner

Uncertain adherence to treatment

Do not use NAAT sooner than 3- 4 weeks

Rescreen anyone with a positive test 3 months post treatment High rates of reinfection (not treatment failure)

Gonorrhea—Rates by Sex, United States, 1991–2011

2011-Fig 17. SR

GC: Tremendous Disparities By race: Rates in African Americans >20x those in whites

By sexual orientation: MSM rates16x those in heterosexual men in King County

CDC Guidelines 2010: CT & GC Screening for Men

Selective male chlamydia screening in high prevalence settings Adolescent clinics, correctional facilities, STD clinics, military

MSM A test for urethral GC and CT if insertive intercourse in past year* A test for rectal GC and CT if receptive intercourse in past year* A test for pharyngeal GC if receptive oral sex in past year

Rescreen anyone with a positive test 3 months after treatment

*regardless of reported condom use

MSM: Extra-genital Screening is Key

N=6434 men

53% of chlamydia and 64% of gonorrhea cases would be missed with urethral screening only

Site % of all GC cases*

% of all CT cases*

Urethra 21 29

Rectum 15 54

Pharynx 36 7

Rectum & Pharynx 12 4

Rectum & Urethra 6 6

Urethra & Pharynx 5 <1%

All 3 sites 5 <1%

Kent CK, et al. CID 2005;41:67-73

NAAT for rectal and pharyngeal testing

>2x sensitivity of culture for rectal and pharyngeal chlamydia and gonorrhea

Not FDA-approved, but can be done if laboratory validation is complete (Lab Corp has done this)

Can use vaginal swab for these sites

Weekly / Vol. 61 / No. 31 gust 10, 2012

Update to CDC’s STD Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections

Uncomplicated genital track or rectal gonorrhea

RECOMMENDED

Ceftriaxone 250 mg IM

PLUS

Azithromycin 1g po x 1 OR doxycycline 100mg po bid x 7d

ALTERNATIVE

Cefixime 400mg po x 1

PLUS

Azithromycin 1g po x 1 OR doxycycline 100mg po bid x 7d

PLUS

Test of Cure in 1 week

Rationale for Treatment Recommendations

• Pharyngeal infections• ~30% of MSM and women with genital tract gonorrhea

also have pharyngeal infection

• Oral cephalosporins have poor penetration

• Decreased susceptibility to oral cephalosporins• Multi-drug resistant (PCN, quinolones, azithromycin)

• Ceftriaxone still extremely effective

• Higher doses of ceftriaxone and dual agent use may discourage development of resistance

Percentage of N. gonorrhoeae Isolates with Elevated MICs to Oral Cephalosporins, 2005- June 2011

Source: Gonococcal Isolate Surveillance Project

Distribution of Minimum Inhibitory Concentrations (MICs) of Ceftriaxone Among Neisseria gonorrhoeae Isolates, Gonococcal

Isolate Surveillance Project (GISP), 2007–2011

2011-Fig 30. SR

Percentage of PHSKC STD Clinic Patients with Pharyngeal Gonococcal Testing Positive for N. gonorrhoeae within 180 Day of Treatment

4

31

12

25

0

10

20

30

40

50

• Patients diagnosed by culture 1993-2009 - Passive follow-up• Patients treated with cefixime or cefpodoxime 400mg • 277/817 (34%) patients retested – No variation by treatment regimen

Cephalo + AZM

Cephalo + Doxy

AZM Alone

Cephalo Alone

N=119 N=62 N=21 N=48

Per

cent

P<0.05 Cephalo+AZM vs Cephalo

Alone or with Doxy

Percentage Patients Retesting Positive

Source: Golden. ISSTDR 2009

Gonorrhea Treatment Summary Decreased susceptibility to oral cephalosporins is primarily

a concern for MSM

No gonococci in US are resistant to ceftriaxone (yet)

Decreased susceptibility strains are rare in heterosexuals

Recommendations: All patients with GC should be treated with ceftriaxone and

azithromycin (preferable to ceftriaxone + doxycycline)

Continue EPT for heterosexuals with oral cephalosporins

MSM should not receive EPT

All patients with GC should be rescreened 3 months after treatment

Gonorrhea Summary & Treatment Recommendations

• No gonococci in the U.S. are resistant to ceftriaxone• Decreased susceptibility to cefixime remain very rare in heterosexuals• Recommendations:

• Ceftriaxone + Azithro is first choice – NOT doxy• Cefixime/Azithro is reasonable alternative when

IM therapy is not an option (try to avoid in MSM)• Test of cure only indicated for:

• Persistent signd/symptoms• Pharyngeal GC treated with non-ceftriaxone

regimen• Pregnant women

• EPT recommendations unchanged – NO EPT in MSM

• Rescreen all patients at 12 weeks

Non-gonococcal urethritis

ORGANISMS DETECTED in MEN with NGU

Seattle MEGA Trial (n=524)

NIH Trial (n=305)*

C. trachomatis 26% 43%

M. genitalium 14% 31%

U. ureealyticum-biovar 2 24%

T. vaginalis 2% 21%

Idiopathic 38% 29%

* Birmingham, AL; Baltimore, MD; New Orleans, LA; Durham, NC.

Randomized Trials of Azithromycin vs. Doxycycline for NGU: Clinical Cure

78757784

69

81

0

20

40

60

80

100

Stamm Schwebke* Manhart

Doxy Azithromycin

Per

cent

Cur

ed

Manhart L. CDC STD Prevention Conference 2012

Randomized Trials of Azithromycin vs. Doxycycline for NGU: M. genitalium Microbiologic

Cure

3031

4540

67

87

0

20

40

60

80

100

Mena* Schwebke* Manhart

Doxy Azithromycin

Per

cent

Cur

ed

*P<.05 Manhart L. CDC STD Prevention Conference 2012

Persistent NGU Treatment

Initial Rx: Doxy or Azithro

? Defined etiology, reexposure/partner treatment

Document evidence of inflammation – positive GS or urine LE

If positive – Treat with Doxy or Azithro +/- Metronidazole

(+/- trich culture)

? Defined etiology, reexposure/partner treatment

Document evidence of inflammation – positive GS or urine LE

If positive – Treat with Moxifloxicin 400mg po qd x 7

Initial Rx: Doxy or Azithro

? Defined etiology, reexposure/partner treatment

Document evidence of inflammation – positive GS or urine LE

If positive – Treat with Moxifloxicin 400mg po qd x 7

Seattle ApproachCDC Approach

Syphilis

Primary and Secondary Syphilis—Rates by Sex and

Male-to-Female Rate Ratios, United States, 1990–2011

2011-Fig 38. SR

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

0

50

100

150

200

250

300

350

400

2 2 1 532

60 58 50 6077

140

179 174188 185

145

263

376

163 1

154 9 12

2 3 526

13 10 5 6 9 13

MSM syphilis**

Heterosexual syphilis

Ea

rly

syp

hili

s ca

ses

King County: Early syphilis*, 1994-2011

*Reported P, S, and EL syphilis**Excludes some male cases with unknown MSM status

Syphilis – A Brief Refresher

Few hours: lymph -> bloodstream

Chancre ~ 3 weeks (10-90

days) spontaneously heals

1-6 weeks later

Syphilis – A Brief Refresher

Few hours: lymph -> bloodstream

Chancre ~ 3 weeks (10-90

days) spontaneously heals

1-6 weeks later

3-6 weeks after chancre

15% overlap

Transmission

Risk: ~30% per sex act

(compared to 0.07-2% per sex anal sex act for HIV*)

*Cassels et al, AIDS 2009;23:2497

Reverse Sequence Syphilis Screening Algorithm

• Why? Decreased cost for the laboratory

• Traditional• Screen with nontreponemal test (RPR or VDRL)• Confirm with a treponemal specific test (TPPA, MHATP)

• Reverse• Screen with treponemal specific EIA • Confirm with RPR• If conflict: resolve with older treponemal test (TPPA)

EIA Screening Algorithm

EIA or CLIA

No Syphilis

NegativePositive or Equivocal

RPR

Syphilis-early disease

-past infection (treated)-untreated, long duration

Positive

TP-PA

Negative

Negative

Unlikely syphilisProbably false positive EIA

But if high suspicion, repeat in 1 month

Positive

Syphilis

Reverse Sequence Syphilis Screening

Total

Low Prevalence Pops

High Prevalence Pops

EIA +

3.4%

2.3%

14.5%

RPR- Among EIA+ (Old Syphilis or False+)

57%

61%

51%

TPPA- Among RPR- (False+)

32%

41%

14%

MMWR 2011;60:133

Geographical Distribution of Endemic, Non-venereal Treponematoses

Vaginitis

Key Features of Normal Vaginal Environment

Normal pH <4.7: Maintained by dominant vaginal bacteria,

Lactobacillus, that produce lactic acid Favors growth of lactobacilli and inhibits growth of

other organisms (residents and invaders) Human lactobacilli

Major species: L. crispatus and L. jensenii Need to produce hydrogen peroxide (H2O2) for

maximal benefit

Vaginitis Very common National Health and Examination Survey (ages 14-49)

28% of women reported symptoms BV prevalence: 27%

White women: 23% Non-Hispanic black women: 51%

Trichomonas prevalence 3% White women: 1% Non-hispanic black women: 13%

Top 3 causes Bacterial Vaginosis Candidiasis Trichomoniasis

Koumans, STD 2007Sutton, Clin Infect Dis 2007

Diagnosis Lack of specificity in clinical presentation = syndromic

diagnosis doesn’t work

A pH-Based Framework for Evaluating Common Causes of Vaginitis

Nyirjesy & Sobel, Curr ID Reports 2005

Bacterial Vaginosis: Dx Typical discharge: homogenous, greyish, adherent to

vaginal epithelium

Clinical findings (Amsel criteria): 3 of the following must be present: homogeneous discharge pH >4.5 clue cells (>20%) amine odor on addition of KOH (+whiff test)

PCR amplification of vaginal bacteria

Fredricks et al. NEJM Nov 2005; 368:1899-1911

BV negative BV positive

Vaginitis Treatment BV

Metronidazole 500mg po BID x 7 days Or gel 0.75% vaginally QD x 5 days

Or clindamycin cream 2% vaginally x 7 days 15-20% of women fail initial treatment ~75% recurrence over 1 year

Trichomonas Metronidazole 2g po x 1 Or tinidazole 2g po x 1 ($) Nitroimidazole resistance: only useful drug

class

Time to BV Recurrence (ITT), Biweekly MTZ Gel vs. Placebo

Sobel AJOG 2006

Herpes

HSV-2 Seroprevalence in U.S.

AW-245 8-13-1996

Pre

vale

nce

(%)

MMWR 59 (15), 2010

Herpes: Key Points Most persons with HSV do not know they have it

Do not have or do not recognize symptoms

Most transmission occurs by subclinical genital shedding

Distinct from unrecognized infection

Suppressive antiviral therapy decreases, but does not eliminate risk of transmission

Know how to interpret serology results

Genital Ulcers – Exam is non-specific

Sensitivity/Specificity

Incubation Primary Lesion

Base Size Edges Induration Pain

Herpes 2-7 days ≥3 lesions Erythematous, serous

1-2mm Erythematous None Tender

Syphilis 9-90 days Papule (one)

Smooth,Non-purulent

5-15mm Elevated, Demarcated

Firm Non-tender

47%/95%

63%/64%

67%/58%

60%/50%

DiCarlo RP, CID 1997;25:292

Classic herpes triad (≥3 superficial, tender lesions): 94% specificity, but seen only in a minority of patients

Herpes Testing: Lesions Test to confirm diagnosis Highest yield: vesicles,

pustules (early lesions) Unroof & scrape base

PCR more sensitive than culture (N>36,000 samples)Sensitivity False

positiveSpecificity

Viral Culture 24% 76%

PCR 99.9 0.1% 100

Ratio PCR:Viral culture positivity3.1 (presence of

lesions)5.1 (absence of

lesions)Wald et al JID 2003: 188

Slide adapted from Christine Johnston, MD

Herpes Testing: Serology Type-specific serology tests may be useful:

Recurrent/atypical symptoms with negative culture Clinical diagnosis without lab confirmation Patients with a partner with genital HSV

Median time to seroconversion: 3 weeks Upper limit: 4 months

HSV-2 serologic testing can be offered to persons presenting for a STD evaluation Personal health service Screening for HSV-1 or HSV-2 in the general

population is not indicated.

Type-Specific gG-Based HSV Serology: Commercial Kits 2012

Sensitivity Specificity

HerpeSelect-2 ELISA (Focus) 96-100* 97-100

HerpeSelect Immunoblot (Focus) 97-100 98

HerpeSelect Express (Focus) 86-100 97-100

biokitHSV-2 (biokitUSA ) 93-100 94-97

Cobas-HSV-2 (Roche) 93 98

Captia Select-HSV-2 (Trinity) 90-92 91-99

• Cost varies; $30-$180• Western blot assay, considered gold standard, available through University of

Washington

Median time to seroconversion: 3 wk (<4m)

89

63

85

78

0

20

40

60

80

100

98% Specificity

Pos

itive

Pre

dict

ive

Val

ue (

%)

Prevalence

False Positive HerpesSelect: A function of prevalence

5% 15%10% 20%

Interpreting Common Serologies

HerpeSelect (Focus) ELISA is commonly used Although package insert states that an index value

>1.1 should be interpreted as positive, several experts use a cutoff of 3.5 PPV as low as 38% in college students with very low HSV2

seroprevalence (3.4%) [Mark 2007] Leads to higher negative predictive value [Golden 2005;

Philip 2008] Correctly reports uninfected people as uninfected Fewer false positives

For patients who REALLY want to know, consider Western blot Call #206-598-6066 to request HSV Type-Specific Serology

information packet http://depts.washington.edu/herpes/

Herpes Serology: Limitations

Does not tell How long infected If person has had or will have symptoms How likely a person is to shed asymptomatically Where infected (HSV-1)

Cannot diagnose a lesion False positives

Decreased PPV in low prevalence populations AND in patients with HSV-1 infection

False negatives 77% of patients have antibodies by 6 weeks after

HSV-2 primary infection and 59% after HSV-2 non-primary infection.

Herpes Serology

No role for IgM No role for non-type specific IgG tests

Which Patients Should Receive Suppressive Antiviral Therapy?

Frequent recurrences Psychological distress Acyclovir – excellent safety for 10 years

No need to monitor safety labs or to caution women against getting pregnant while taking it

Famciclovir and Valacyclovir – safety for 1 year Higher bioavailability (GI absorption) allows less

frequent dosing) Consider discontinuation after 1 year

To observe rate of recurrence To monitor adjustment to recurrences

No evidence of emergence of resistant strains in immunocompetent persons

Prevention strategies for HSV-2

Disclosure of serostatus Avoid sex with lesions (imperfect, but

higher viral load when present) Condoms Antiviral therapy Vaccine (may prevent HSV1 in women;

Belshe NEJM 2012) Topical microbicides…stay tuned

• Can’t predict with symptoms as guidance (Wald 1995)

• Frequency of shedding higher with history of symptomatic outbreaks (20% of days), but still 10% of days in asymptomatic persons (Tronstein 2011)

• Shedding most frequent first year after initial outbreak, but persists for years after

Asymptomatic Shedding & Transmission

• Most transmissions from persons without clinical history of genital herpes

• Subclinical Recurrences• Viral shedding 10% of asymptomatic

days • Suppressive therapy can prevent

transmission

Corey et al. N Engl Jour Med 2004; 350 (1): 11-20

No Medica-tion

SD-ACV SD-VAL HD-ACV SD-VAL HD-VAL0

5

10

15

20

25P

erc

en

t o

f sw

ab

s w

ith H

SV

de

tect

ed

Trial 1IRR=0.05

95% CI=0.03-0.08, p<0.001

Trial 2IRR=0.79

95% CI=0.63-1.00, p=0.052

Trial 3IRR=0.54

95% CI=0.44-0.66, p=0<0.001

Estimated 0 7.7 10 25 10 88Acyclovir AUC

Genital HSV-2 Shedding Rate

Johnston, JAMA 2012

No Medica-tion

SD-ACV SD-VAL HD-ACV SD-VAL HD-VAL0

5

10

15

20

25P

erc

en

t o

f sw

ab

s w

ith H

SV

de

tect

ed

Trial 1IRR=0.05

95% CI=0.03-0.08, p<0.001

Trial 2IRR=0.79

95% CI=0.63-1.00, p=0.052

Trial 3IRR=0.54

95% CI=0.44-0.66, p=0<0.001

Estimated 0 7.7 10 25 10 88Acyclovir AUC

Genital HSV-2 Shedding Rate

Johnston, JAMA 2012

• Frequent short bursts of HSV-2 reactivation occur in the presence of both standard dose suppressive antivirals and on high dose therapy– While shedding frequency and quantity is reduced on high dose

valacyclovir, breakthrough shedding occurs at a similar episode rate on all doses

• Antiviral therapy, though clinically effective, does not alter the underlying pathobiology of frequent HSV-2 reactivation

Counseling the Newly Diagnosed Patient with HSV2

Consider serologic testing of partner(s) Recognize risk of subclinical shedding Discuss value of suppressive antiviral

therapy Effective in reducing outbreaks, reducing

BUT NOT ELIMINATING days with shedding Discuss other preventive measure

Condoms Avoiding sex with outbreaks

Things to You Might Want to Say

I know this must be really hard news for you to hear

This is a manageable disease, even though there is no cure yet

You are not alone—1 in 4 adults is infected with HSV-2

Genital herpes is usually not associated with serious health issues, including effects on reproductive health

Give yourself some time to adjust; don’t expect it to happen overnight

There are a lot of good resources online

Miscellaneous Key Points

HPV Vaccine

Don’t Miss Acute HIV

HIV Testing Regulations

Take-Home Points

Screen women <26 for chlamydia annually Offer heterosexuals with GC and CT EPT Treat gonorrhea with ceftriaxone + azithromycin Rescreen for GC and CT 3 months after treatment Be vigilant for syphilis among MSM

Social history should include gender of sex partners

Syphilis EIA has high false positive rate in low prevalence populations

Know how to interpret your herpes serologic test Index values are key

Most herpes is transmitted through subclinical shedding and most people with herpes don’t know they have it

Thank Youjdombrow@uw.edu

Acknowledgements Jeanne Marrazzo, MD, MPH Matthew Golden, MD, MPH Devika Singh, MD, MPH Sue Szabo, PA Christine Johnston, MD, MPH Joanne Stekler, MD, MPH Caroline Mitchell, MD CDC (slides)

STD Web Resources

Herpes Web resources

ASHA patient herpes hotline (919) 361-8488

University of Washington Viral Diseases Research Clinic (206) 720-4340

www.ashastd.org reading materials www.herpeshelp.com Glaxo web site www.westoverheights.com handbook www.healthcheckusa.com order own tests www.herpesdiagnosis.com diagnosis data www.herpeshomepage.com posts, pharmacy link