1. STD Cases for HIV Care Providers
Sharon Adler, MD MPH
STD Control Branch, California Department of Public Health
California STD/HIV Prevention Training Center

2. Disclosure Information
STD Cases for HIV Care Providers
Sharon Adler MD, MPH
I have no financial relationships to disclose
-and
I will discuss off label use of NAAT tests for GC/CT
pharyngeal and rectal testing.

3. Overview
• Screening recommendations
• Gonorrhea
• Chlamydia
• Trichomoniasis
• M. genitalium
• Syphilis

4. Jeremy
• 23 year-old HIV+, CD4 500 , VL undetectable at initial
evaluation ~4 months ago
• Here for HIV RNA testing
• Asymptomatic

5. ARS Question:
Should you offer STD Screening
for this patient?
A. Yes
B. No
C. Not at this visit
D. Not sure

6. STI Screening Recommendations:
HIV-positive Men
STI Anatomic Site Frequency
Chlamydia 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 visit
Hep B sAg Serology First visit
Hep 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.

7. STI Screening Recommendations:
HIV-positive Women
STI Anatomic Site Frequency
Chlamydia 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 visit
Hep B sAg Serology First visit
Hep 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.

8. 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

9. 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

10. Chlamydia and gonorrhea
NAA Testing
…not FDA-cleared for rectal or
pharyngeal specimens but now the
preferred testing method over culture
Validation procedures can be done by labs to allow
use of a non-FDA-cleared test or application

11. 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

12. How common are CT and GC infections
among MSM seeking STD testing?
12
9.4
10 8.8
7.5
8 6.6
5.5 Urethral
6 Rectal
Pharyngeal
4
1.3
2
0
Chlamydia Gonorrhea
Kent, CK et al, Clin Infect Dis 2005;41:67–74

13. Majority of Rectal Infections in MSM seeking
STD Services are Asymptomatic
Rectal
Infections
86% 84%
Chlamydia Gonorrhea
n=316 n=264 Asymptomatic
Symptomatic
Urethral 10%
Infections
42%
Chlamydia Gonorrhea
n=315 n=364
Kent, CK et al, Clin Infect Dis July 2005

14. 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

15. 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/treatment
2).Revised Recommendations for HIV Testing of Adults, Adolescents, and
Pregnant Women in Health-Care Settings MMWR Sept 2006; 55 (RR14):1-17

16. Jeremy
Review of Test Results:
• Rectal GC Positive
• Rectal CT Negative
• Urine GC/CT Negative
• Pharyngeal GC Negative
• Syphilis Serology non-reactive

17. ARS Question:
How would you treat this patient?
A. Ceftriaxone 125 mg IM
+ azithromycin 1 g PO
B. Ceftriaxone 250 mg IM
C. Ceftriaxone 250 mg IM
+ azithromycin 1 g PO
D. Azithromycin 1 g PO

18. Antibiotic-Resistant
Gonorrhea

19. 3 Changes to Gonorrhea
Treatment in 2010
1. Ceftriaxone IM preferred over oral
cephalosporins
2. Ceftriaxone dose increased to 250 mg
3. Dual treatment for gonorrhea regardless of
chlamydia test result
CDC 2010 STD Treatment Guidelines
www.cdc.gov/std/treatment

20. 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 result
IN CASE OF SEVERE ALLERGY:
Azithromycin 2 g orally once
CDC 2010 STD Treatment Guidelines
www.cdc.gov/std/treatment

21. Gonorrhea Treatment
Oropharyngeal Infections
Azithromycin
Ceftriaxone 250 mg 1 g orally
IM in a single dose PLUS
or
Doxycycline
100 mg BID x
7 days
IN CASE OF SEVERE ALLERGY:
 Azithromycin 2 g orally once
CDC 2010 STD Treatment Guidelines
www.cdc.gov/std/treatment

22. Treatment Efficacy for
Pharyngeal Gonorrhea
DRUG AND DOSE EFFICACY Lower 95% CI
Ceftriaxone 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.

23. 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
Year
NOTE: Resistant isolates have ciprofloxacin minimum inhibitory concentrations (MICs) >1 µg/ml. Isolates
with intermediate resistance have ciprofloxacin MICs of 0.125–0.5 µg/ml. Susceptibility to ciprofloxacin was
first measured in GISP in 1990.

24. Cephalosporin Susceptibility Among Neisseria gonorrhoeae Isolates-
US, 2000-2010. MMWR/July 8,2011/Vol. 60/No. 26

25. Proportion of isolates with
MICs to Cefixime ≥ 0.25 μg/ml
by Region
4 n=52,785 3.3%
(n=68)
*
Northeast & South
Percentage 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)

26. • 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

27. 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

28. Nadinewoman
A 26 y.o. HIV+
presents with c/o vaginal discharge.
• Motile trichomoniasis seen on wet
mount
• GC/CT vaginal swab NAAT

29. ARS
For this HIV+ patient, what regimen would
you use to treat trichomoniasis?
A. Metronidazole 2 gm
PO x1
B. Tinidazole 2 gm PO x1
C. Metronidazole 500 mg
PO BID x 7 days
D. Metronidazole 2 gm
PO x 5 days

30. Trichomoniasis Treatment
Recommended regimen:
 Metronidazole 2 g PO x 1
 Tinidazole 2 g po x 1
Consider treating HIV-infected women:
 Metronidazole 500 mg PO BID x 7d
Alternative regimen:
 Metronidazole 500 mg PO BID x 7d
Recommended regimen in pregnancy:
Metronidazole 2 g PO x 1
Note: Vaginal therapy is ineffective
Tinidazole is a Category C drug in pregnancy
CDC 2010 STD Treatment Guidelines
www.cdc.gov/std/treatment

31. Trichomoniasis
Recurrence/ Resistance
• Cure rate over 90%
• Assess drug adherence, re-exposure
• Low-level metro resistance 2%–5% ; High-level
resistance rare
• Most respond to tinidazole or higher
doses 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)

32. Newer Trichomonas Diagnostics
Test Sensitivity Specificity
OSOM >83% >97% 10 min
POC
Affirm VPIII >83% >97% 45 min
POC
Aptima* 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

33. Nadine
Laboratory Results
• GC vaginal swab negative
• CT vaginal swab Positive

34. Major Conclusions
NAATs recommended
Optimal screening specimen types are:
First catch urine for men
Self collected swabs from women
NAATs recommended for
detection of rectal and
oropharyngeal infections in MSM
Anticipated release of final guidelines
expected early 2012

35. Chlamydia Treatment
Adolescents and Adults
Recommended regimens (nonpregnant):
 Azithromycin 1 g orally in a single dose
 Doxycycline 100 mg orally twice daily for 7 days
Recommended 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

36. 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

37. The Effectiveness of Expedited Partner
Treatment on Re-Infection Rates
GONORRHEA CHLAMYDIA
20% P=.02 P=.17
15%
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.

38. Percent of Partners Treated by Partner Management
Strategy, California FP Clinics, 2005-2006
Percent 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

39. CT/GC Partner Management
Strategies
Gaps:
▪ 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)

40. Legal Status of EPT in the U.S.
PERMISSIBLE
27 states
UNCERTAIN
15 states
PROHIBITED
8 states
CDC EPT Legal Status Updated November 2010
www.cdc.gov/std/ept

41. Counseling and Printed Materials to
Reduce EPT Risks
POTENTIAL RISK PATIENT INFO
Undiagnosed Referral to care for STD/HIV
coinfection with STD or testing
HIV
Treatment failure Referral to care
Female partner with PID Warning to females with
or pregnancy pelvic pain or possible
pregnancy
Allergy to medication Warning to not take
medication and seek care

42. ARS Question
After patient treated for chlamydia, when
should she return?
A. 1 week for a TOC
B. 3 weeks for a TOC
C. 3 months for a test
for reinfection
D. 1 year for her annual
exam
E. Not sure

43. 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

44. Rapid Repeat Chlamydial Infection
is Common in Women
40
Retesting
Prevalence
Reinfection (%)
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

45. Chlamydia and Gonorrhea Reinfection
in Men within 6 Months
35
30.8 Chlamydia
30
Gonorrhea
25
20
16.0
14.9
15
10.7 11.4 11.1
9.8 10.1
10
7.0
5
0 0
0
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

46. 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

47. ARS
What treatment should he receive?
A. Ceftriaxone 250 mg IM +
azithromycin 1 g PO
B. Doxycycline 100mg PO BID x 7
days
C. Levofloxacin 500 mg PO daily x
7 days
D. Metronidazole 2 gm PO x 1
E. Retest today, no treatment
needed

48. 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

49. 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

50. Persistent NGU Treatment
Recommended 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 NGU
treatment failures due to M. genitalium
CDC 2010 STD Treatment Guidelines
www.cdc.gov/std/treatment

51. 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 ago
Results: RPR non-reactive
HSV PCR-negative

52. ARS
Can he have syphilis with a
negative RPR?
A. Yes
B. No
C. Not Sure
0% 0% 0%
s
No
re
Ye
Su
t
No

53. Management Issues
in Primary Syphilis
Serology 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

54. Relative Sensitivity of Screening Tests:
Darkfield+ Primary Syphilis Cases,
SF 2002-2004
Testing Overall Sensitivity: Sensitivity: P
Approach sensitivity HIV– HIV+ Value
(N=106) (N=65) (N=29)
VDRL with
reflex to 71% 77% 55% .05
TPPA
TPPA as
first-line 86% 88% 83% .53
test
Creegan et al. STD 2007: 34: 1016-8.

55. 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

56. Syphilis Staging Flowchart
SYPHILIS SIGNS /SYMPTOMS?
YES NO
Asymptomatic .
Chancre LATENT
Rash,
PRIMARY Condyloma,etc.
SECONDARY

57. 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

58. 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 failure
In HIV infection, unless neurologic symptoms,
there is no evidence that CSF exam is
associated with improved outcomes
CDC 2010 STD Tx Guidelines
www.cdc.gov/std/treatment

59. Syphilis Treatment
Primary, Secondary & Early Latent:
Benzathine penicillin G 2.4 million units IM in a single
dose
Late 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 intervals
Neurosyphilis:
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

60. Online STD Resources
CDC Treatment Guidelines
www.cdc.gov/std/treatment
California STD/HIV Prevention Training
Center
www.stdhivtraining.org
California Department of Public Health
STD Control Branch
www.std.ca.gov

61. THANK YOU!
Chlamydia
HPV Syphilis
HSV-2
Gonorrhea
HIV