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STD Cases for HIV Care Providers Sharon Adler, MD MPHSTD Control Branch, California Department of Public Health California STD/HIV Prevention Training Center
Disclosure Information STD Cases for HIV Care Providers Sharon Adler MD, MPHI have no financial relationships to disclose -andI will discuss off label use of NAAT tests for GC/CT pharyngeal and rectal testing.
Overview• Screening recommendations• Gonorrhea• Chlamydia• Trichomoniasis• M. genitalium• Syphilis
Jeremy• 23 year-old HIV+, CD4 500 , VL undetectable at initial evaluation ~4 months ago• Here for HIV RNA testing• Asymptomatic
ARS Question: Should you offer STD Screening for this patient?A. YesB. NoC. Not at this visitD. Not sure
STI Screening Recommendations: HIV-positive MenSTI Anatomic Site FrequencyChlamydia Urine or urethral Annually* Rectal, if exposed Annually*Gonorrhea Urine or urethral Annually* Rectal and pharyngeal, if exposed Annually*Syphilis Serology Annually*HSV-2 Serology First visitHep B sAg Serology First visitHep C Serology First visit* Repeat screening every 3-6 months as indicated by risk.Consider anal Pap screening for MSM. Primary Care Guidelines for the Management of Persons Infected with HIV: 2009 Update by the HIVMA of the IDSA. Clin Infect Dis 2009;49, 651-681.
STI Screening Recommendations: HIV-positive WomenSTI Anatomic Site FrequencyChlamydia Vaginal, urine, or cervical Annually* Rectal, if exposed Annually*Gonorrhea Vaginal, urine, or cervical Annually* Rectal and pharyngeal, if exposed Annually*Syphilis Serology Annually*Trichomoniasis Vaginal Annually*HSV-2 Serology First visitHep B sAg Serology First visitHep C Serology First visit* If sexually active; repeat every 3-6 months as indicated by risk.Cervical Pap screening; Consider anal Pap if hx of dysplasia. Primary Care Guidelines for the Management of Persons Infected with HIV: 2009 Update by the HIVMA of the IDSA. Clin Infect Dis 2009;49, 651-681.
STD Screening for MSM• HIV• Syphilis• Urethral GC and CT *• Rectal GC and CT (if RAI)• Pharyngeal GC (if oral sex)• HSV-2 serology (consider)• Hepatitis B (HBsAg)• Anal Pap (consider for HIV+)* At least annually, more frequent (3-6 months) if at high risk(multiple/anonymous partners, drug use, high risk partners) CDC 2010 STD Tx Guidelines www.cdc.gov/std/treatment
Nucleic Acid Amplification Tests* Highest sensitivity for Chlamydia Able to detect 30-40% more infections Detects more GC at all sites Less dependent on specimen collection and handling Self-collected vaginal swabs Urine Liquid PAP *NAATs Roche Amplicor (PCR) GenProbe Aptima (TMA) B-D ProbeTec (SDA)All FDA cleared for liquid pap transport media CDC 2010 STD Treatment Guidelines Schachter J, et al. Sex Transm Dis 2008; 35: 637‐42
Chlamydia and gonorrhea NAA Testing …not FDA-cleared for rectal or pharyngeal specimens but now the preferred testing method over cultureValidation procedures can be done by labs to allowuse of a non-FDA-cleared test or application
NAAT Laboratory Ordering and Billing Codes Company-Specific Ordering Codes for Company-Specific Combined GC/CT Nucleic Acid Amplified Ordering Codes for CT Tests (NAATs) test only LabCorp* Quest* LabCorp Rectal 188672 16506 188706 Pharyngeal 188698 70051 188714 NAATs are offered at (or from) any location in the country with these two codes. For information on specimen collection and transportation, clinicians should contact the local reference laboratory representative. CPT Billing Codes CT detection by NAAT 87491 GC detection by NAAT 87591 *CDC does not endorse these laboratories, however, they represent the largest laboratories nationally. There may be other private laboratories that have verified rectal and pharyngeal testing with NAATs. Many PHLs have also verified rectal and pharyngeal testing.CLIA Verified Labs for non-genital CT and GC NAATs list on NNPTC website ( www.stdhivpreventiontraining.org)under Training Resources/Clinical Practice References. Bolan, CDC webinar March 2011
How common are CT and GC infections among MSM seeking STD testing?12 9.410 8.8 7.58 6.6 5.5 Urethral6 Rectal Pharyngeal4 1.320 Chlamydia Gonorrhea Kent, CK et al, Clin Infect Dis 2005;41:67–74
Majority of Rectal Infections in MSM seeking STD Services are AsymptomaticRectalInfections 86% 84% Chlamydia Gonorrhea n=316 n=264 Asymptomatic SymptomaticUrethral 10%Infections 42% Chlamydia Gonorrhea n=315 n=364 Kent, CK et al, Clin Infect Dis July 2005
Proportion of CT and GC infections MISSED among 3398 asymptomatic MSM if screening only urine/urethral sites, San Francisco, 2008-2009 Identified Identified 23% 5% MISSED MISSED 77% 95% Chlamydia Gonorrhea Marcus et al, STD Oct 2011; 38: 922-4
HIV Screening Recommendations • Screen for HIV in all persons being evaluated for or being treated for an STD 1 • Routine opt-out HIV screening for all patients aged 13-64 years, in all health-care settings 2 – Unless prevalence of undiagnosed HIV infection in that setting is documented to be <0.1%1).CDC 2010 STD Tx Guidelines www.cdc.gov/std/treatment2).Revised Recommendations for HIV Testing of Adults, Adolescents, andPregnant Women in Health-Care Settings MMWR Sept 2006; 55 (RR14):1-17
JeremyReview of Test Results:• Rectal GC Positive• Rectal CT Negative• Urine GC/CT Negative• Pharyngeal GC Negative• Syphilis Serology non-reactive
ARS Question: How would you treat this patient?A. Ceftriaxone 125 mg IM + azithromycin 1 g POB. Ceftriaxone 250 mg IMC. Ceftriaxone 250 mg IM + azithromycin 1 g POD. Azithromycin 1 g PO
3 Changes to Gonorrhea Treatment in 20101. Ceftriaxone IM preferred over oral cephalosporins2. Ceftriaxone dose increased to 250 mg3. Dual treatment for gonorrhea regardless of chlamydia test result CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Gonorrhea Treatment Uncomplicated Genital/Rectal Infections Ceftriaxone 250 mg IM Azithromycin in a single dose 1 g orally PLUS* or OR, if not an option: Doxycycline Cefixime 400 mg orally 100 mg BID x in a single dose 7 days * Regardless of CT test resultIN CASE OF SEVERE ALLERGY: Azithromycin 2 g orally once CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Gonorrhea Treatment Oropharyngeal Infections Azithromycin Ceftriaxone 250 mg 1 g orally IM in a single dose PLUS or Doxycycline 100 mg BID x 7 daysIN CASE OF SEVERE ALLERGY: Azithromycin 2 g orally once CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Treatment Efficacy for Pharyngeal GonorrheaDRUG AND DOSE EFFICACY Lower 95% CICeftriaxone 250 mg IM 99% 94%Ceftriaxone 125 mg IM 94% 86%Cefixime 400 mg PO 92% 75%Azithro 2 g PO 96% 76%*Cefixime 400 mg PLUS 100% 92%**Azithro 1 g PO Moran JS, Levine WC. Clin Infect Dis 1995;20 Suppl 1:S47–S65. Newman LM, Moran JS, Workowski KA. Clin Infect Dis 2007;44 Suppl 3:S84–101. * Dan M, Poch F, Amitai Z, STD, 2006;33 (8); small sample size N=21. ** L. Newman, unpublished data; small sample size N=36.
Gonococcal Isolate Surveillance Project (GISP)— Percentage of Neisseria gonorrhoeae Isolates with Resistance or Intermediate Resistance to Ciprofloxacin, 1990–2009 Percentage 20 15 Fluoroquinolones 10 5 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 YearNOTE: Resistant isolates have ciprofloxacin minimum inhibitory concentrations (MICs) >1 µg/ml. Isolateswith intermediate resistance have ciprofloxacin MICs of 0.125–0.5 µg/ml. Susceptibility to ciprofloxacin wasfirst measured in GISP in 1990.
Proportion of isolates with MICs to Cefixime ≥ 0.25 μg/ml by Region 4 n=52,785 3.3% (n=68) * Northeast & SouthPercentage of isolates 3 Midwest West 2 1 * * 0 2000 01 02 03 04 05 06 07 08 09 2010 * p trend < 0.05 Preliminary data CDC:: Gonococcal Isolate Surveillance Project (GISP)
• Cephalosporin treatment failures described only with pharyngeal infection• July 2011: high level ceftriaxone resistance reported (MIC=2.0-4.0) from pharyngeal culture of Kyoto sex worker Unemo Eurosurveillance 2011 | Tapsall J Med Microbiol 2009 | Ohnishi EID 2011
Suspected GC Treatment Failure• Retreat with Ceftriaxone 250mg IM plus Azithromycin 2 gm PO * • Consult ID expert/CDC regarding retreatment for ceftriaxone failure**• Culture TOC within 1 week (NAAT if no culture)• Partner treatment all w/in prior 2 months • test for GC • empirically treat dual therapy Ceftriaxone/Azithro • Report to LHD/State w/in 24 hours*MMWR/ July 8,2011 / Vol 60/No.5 (augments 2010 STD Treatment Guidelines)**Some states have RX recommendations, consult your state/LHD.CDC/State HD website to maintain updated content
Nadinewoman A 26 y.o. HIV+presents with c/o vaginal discharge.• Motile trichomoniasis seen on wet mount• GC/CT vaginal swab NAAT
ARSFor this HIV+ patient, what regimen would you use to treat trichomoniasis?A. Metronidazole 2 gm PO x1B. Tinidazole 2 gm PO x1C. Metronidazole 500 mg PO BID x 7 daysD. Metronidazole 2 gm PO x 5 days
Trichomoniasis TreatmentRecommended regimen: Metronidazole 2 g PO x 1 Tinidazole 2 g po x 1Consider treating HIV-infected women: Metronidazole 500 mg PO BID x 7dAlternative regimen: Metronidazole 500 mg PO BID x 7dRecommended regimen in pregnancy: Metronidazole 2 g PO x 1Note: Vaginal therapy is ineffective Tinidazole is a Category C drug in pregnancy CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Trichomoniasis Recurrence/ Resistance• Cure rate over 90%• Assess drug adherence, re-exposure• Low-level metro resistance 2%–5% ; High-levelresistance rare• Most respond to tinidazole or higherdoses of metronidazole (500 mg p.o. bid x 7d)• Repeated failure: Metronidazole or tinidazole 2 g p.o. x 5d• CDC Consult & T. vaginalis susceptibility (404-718-4141)
Newer Trichomonas DiagnosticsTest Sensitivity SpecificityOSOM >83% >97% 10 min POCAffirm VPIII >83% >97% 45 min POCAptima* 74-98% 87-98% FDA(NAAT) approved April 2011 ( women) Roche Amplicor FDA cleared PCR testing for GC/CT has been modified for T.Vag detection, ok for male urine CDC 2010 STD Treatment Guidelines
Major ConclusionsNAATs recommendedOptimal screening specimen types are: First catch urine for men Self collected swabs from womenNAATs recommended for detection of rectal and oropharyngeal infections in MSMAnticipated release of final guidelinesexpected early 2012
Chlamydia Treatment Adolescents and AdultsRecommended regimens (nonpregnant): Azithromycin 1 g orally in a single dose Doxycycline 100 mg orally twice daily for 7 daysRecommended regimens (pregnant*): Azithromycin 1 g orally in a single dose Amoxicillin 500 mg orally TID x 7 days* Test of cure at 3-4 weeks only in pregnancy CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
CT/GC Partner Management Options Patient referral • Ask patient to notify partner and ensure treatment • Suggest patient bring partner to clinic for concurrent treatment (“BYOP”) • Internet-based anonymous notification Expedited partner treatment (EPT) • Patient-delivered partner treatment (PDPT) • Health department field-delivered treatment • Pharmacy-based Provider or clinic-based referral Health department referral
The Effectiveness of Expedited Partner Treatment on Re-Infection Rates GONORRHEA CHLAMYDIA20% P=.02 P=.1715%10% 13%5% 11% 11% 3%0% Usual Care EPT Usual Care EPT Golden M, et al. N Engl J Med 2005 Feb 17;352(7):676-85.
Percent of Partners Treated by Partner Management Strategy, California FP Clinics, 2005-2006Percent of Partners Treated 100 79 77 80 60 53 40 40 20 12 0 Overall BYOP PDPT Patient None (n=93) (n=131) (n=193) Referral (n=521) Yu Y-Y, et al. STD. 2011 Oct;38(10):913-8
CT/GC Partner Management StrategiesGaps: ▪ Not eliciting all partners ▪ Patient referral What works: • Individualized partner treatment options • Asking client to being partner to clinic (“BYOP”) • Patient-delivered partner treatment (PDPT)
Legal Status of EPT in the U.S. PERMISSIBLE 27 states UNCERTAIN 15 states PROHIBITED 8 statesCDC EPT Legal Status Updated November 2010www.cdc.gov/std/ept
Counseling and Printed Materials to Reduce EPT RisksPOTENTIAL RISK PATIENT INFOUndiagnosed Referral to care for STD/HIVcoinfection with STD or testingHIVTreatment failure Referral to careFemale partner with PID Warning to females withor pregnancy pelvic pain or possible pregnancyAllergy to medication Warning to not take medication and seek care
ARS QuestionAfter patient treated for chlamydia, when should she return?A. 1 week for a TOCB. 3 weeks for a TOCC. 3 months for a test for reinfectionD. 1 year for her annual examE. Not sure
Retesting for Repeat CT/GC Infection• Retest all women and men with CT or GC 3 months after treatment• If client returns earlier than 3 months, consider retest• If client does not return for retesting at 3 months, retest when possible• Test of cure is not recommended, except in pregnancy CDC 2010 STD Tx Guidelines www.cdc.gov/std/treatment
Rapid Repeat Chlamydial Infection is Common in Women 40 Retesting PrevalenceReinfection (%) 30 20 10 Typical Screening Prevalence 0 0 2 4 6 8 10 12 Months Follow-up Hosenfeld C, et al. Sex Transm Dis. 2009 Aug;36(8):478-89
Chlamydia and Gonorrhea Reinfection in Men within 6 Months35 30.8 Chlamydia30 Gonorrhea2520 16.0 14.915 10.7 11.4 11.1 9.8 10.110 7.05 0 00 Peterman 06 Berstein 06 Golden 05 Golden 05 Sparks 04 Dunne 04 Kjaer 00 Systematic Review of 7 Active Cohort Studies, 2000-2006 Fung et al. STI online Dec 2006
Case Scenario:Persistent Urethral Discharge• 22 Year old Male complaint of persistent dysuria & urethral discharge. – Seen 1 week ago and treated for urethritis (Ceftriaxone 250 IM plus Azithromycin 1 gm PO) – States he initially felt a little better but the discharge never really went away. No sexual exposures in past week. – GC/CT NAAT both negative from prior visit• Urethral discharge confirmed on exam today
ARS What treatment should he receive?A. Ceftriaxone 250 mg IM + azithromycin 1 g POB. Doxycycline 100mg PO BID x 7 daysC. Levofloxacin 500 mg PO daily x 7 daysD. Metronidazole 2 gm PO x 1E. Retest today, no treatment needed
Persistent Urethritis: Evaluation • Document urethritis • Rule out noncompliance • Rule out exposure to untreated partner and re- infection • Consider T. Vaginalis* – urethral swab/urine/semen trichomonas culture – Urethral swab/urine for NAAT ( Aptima T.Vag ASR not FDA-cleared; Amplicor T. Vag modified PCR) • Consider doxycylcine-resistant Ureaplasma • Consider M. genitalium* MSM – low probability of T. Vaginalis
Mycoplasma genitalium• Sexually transmitted pathogen• Associated with acute and persistent NGU in men, and endometritis in women• Diagnostic test in development• Azithromycin superior to doxycycline for M. genitalium urethritis – 82% vs 39%• Moxifloxacin effective for persistent NGU caused by M. genitalium CDC 2010 STD Tx Guidelines
Persistent NGU TreatmentRecommended regimens: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose PLUS Azithromycin 1 g orally in a single dose (if not used for initial episode)Moxifloxacin 400 mg PO x 7d effective for NGUtreatment failures due to M. genitalium CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Nathan • 42y/o HIV+ man with mildly painful “sore” on his penis for 3 d • VL undetectable • He remembers getting the skin caught in his zipper • Self-treating with topical antibiotic- no improvement • No history of genital herpes • No syphilis history, RPR negative 10 months agoResults: RPR non-reactive HSV PCR-negative
ARS Can he have syphilis with a negative RPR?A. YesB. NoC. Not Sure 0% 0% 0% s No re Ye Su t No
Management Issues in Primary SyphilisSerology may be negative ~ 25% primary syphilis• Non treponemal tests may have slightly lower sensitivity than treponemal tests in early primary syphilis. – Consider ordering TP-PA along with non-treponemal test• If serology negative and suspicion is low and F/U likely, repeat 2-4 weeks after onset of lesion• If serology negative and suspicion is high, empirically treat and repeat serology 1 week after treatment
Relative Sensitivity of Screening Tests: Darkfield+ Primary Syphilis Cases, SF 2002-2004Testing Overall Sensitivity: Sensitivity: PApproach sensitivity HIV– HIV+ Value (N=106) (N=65) (N=29)VDRL withreflex to 71% 77% 55% .05TPPATPPA asfirst-line 86% 88% 83% .53test Creegan et al. STD 2007: 34: 1016-8.
Syphilis Natural History 30-50% 30%Exposure 10 20 Latent Tertiary 25% Incubation After 3-8 weeks Period 2-6 weeks 2-20 years lesions disappear ~3-4 weeks spontaneously up to 90 days Neurosyphilis can occur at any stage Courtesy: Susan Philip, SF DPH & UCSF
Latent Syphilis Staging Flowchart LATENT SYPHILIS ANY IN PAST YEAR? Negative syphilis serology Known contact to an early case of syphilis Good history of typical signs/symptoms 4-fold increase in titers ( ?Possible treatment failure) Only possible sex exposure this year YES NO EARLY LATENT LATE LATENT or LATENT (< 1 year) of UNKOWN DURATION
When is an LP indicated?• Neurologic, ocular, auditory symptoms/signs • Cranial nerve dysfunction, meningitis, stroke, altered mental status, loss of vibration sense, iritis, uveitis• Evidence of tertiary disease • aortitis, gumma• Serologic treatment failureIn HIV infection, unless neurologic symptoms,there is no evidence that CSF exam isassociated with improved outcomes CDC 2010 STD Tx Guidelines www.cdc.gov/std/treatment
Syphilis TreatmentPrimary, Secondary & Early Latent: Benzathine penicillin G 2.4 million units IM in a single doseLate Latent and Unknown Duration: Benzathine Penicillin G 7.2 million units total, given as 3 doses of 2.4 million units each at 1 week intervalsNeurosyphilis: Aqueous Crystalline Penicillin G 18-24 million units IV daily administered as 3-4 million IV q 4 hr for 10 -14 d *** No enhanced efficacy of additional doses of BPG, amoxicillin or other antibiotics even if HIV infected CDC 2010 STD Treatment Guidelines www.cdc.gov/std/treatment
Online STD ResourcesCDC Treatment Guidelines www.cdc.gov/std/treatmentCalifornia STD/HIV Prevention Training Center www.stdhivtraining.orgCalifornia Department of Public Health STD Control Branch www.std.ca.gov
THANK YOU! ChlamydiaHPV Syphilis HSV-2 Gonorrhea HIV