1. Khalil G. Ghanem, MD, PhD
Associate Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University
School of Medicine
Baltimore, Maryland
Preventing and Managing Sexually
Transmitted Diseases in
HIV-Infected Patients
Supported by educational grants from multiple commercial supporters.

2. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
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3. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e34.

4. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Objectives
 At the end of this presentation, participants should be
able to:
– Recognize critical components of the history and physical
examination of HIV-infected patients that impact STD
screening and management
– Describe recommended approaches to screen for syphilis,
gonorrhea, chlamydia, trichomoniasis, and herpes
– Identify appropriate antimicrobial treatment regimens for
gonorrhea
– Formulate an approach to preventing HPV infections among
HIV-infected persons

5. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Probability of Asymptomatic STDs
Holmes KK, et al. Sex Transm Dis. 4th ed. New York City: McGraw-Hill. 2008.
100
80
60
40
20
0
Urethra/Cervix
Rectum
Pharynx
Urethra/Cervix
Rectum
Pharynx
Urethra/Vagina
Any
Gonorrhea Chlamydia Trich Herpes
Men
Women

6. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Risk Assessment: History and Physical
Examination
 Screening for all STDs is risk based, so accurate information is critical
– Obtain a sexual history in an open, nonjudgmental manner
• Do you have oral sex? Do you use a condom when you have oral sex? vs The last time you
put your mouth on your partner’s penis, did you use a condom? Do you use a condom most
times you do that?
 A sexual history should include:
– Current and past sexual practices (number of partners, gender of partners, all
exposure sites, condom and contraceptive use, past STD history, etc)
– Use of drugs (ETOH, poppers, methamphetamines, etc) with sex
– Risks and status of partners
 A physical examination should include:
– Pelvic examination in women
– Anogenital examination in both men and women
– Careful skin/mucus membrane examination
Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e34.

7. Screening
Chlamydia, Gonorrhea, Trichomoniasis,
Syphilis, and Herpes

8. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Best Specimen Type to Screen for Genital
Gonorrhea and Chlamydia
 Women
– A vaginal swab for
NAATs testing is
preferred
– Endocervical swabs and
urine are acceptable
alternate specimen types
for NAATs testing
– Endocervical swabs are
the only acceptable
specimen type for
gonorrhea cultures
 Men
– First-catch urine for
NAATs testing is
preferred
– Urethral swabs are
acceptable alternate
specimen types for
NAATs testing
– Urethral swabs are the
only acceptable specimen
type for gonorrhea
cultures
MMWR Recomm Rep. 2010;59:1-116.

9. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Why Screen for Extragenital Gonorrhea
and Chlamydia Infections?
 Most cases of pharyngeal and rectal GC and CT are
asymptomatic
 Up to 65% of cases of GC[1,2]
and 50% of cases of CT[2]
among MSM may be missed if genital-only testing were
performed
 In women, 10% of CT and 31% of GC infections would
have been missed if extragenital testing were not done[3]
 Rectal and pharyngeal infections are of public health
significance[4]
1. Gunn RA, et al. Sex Transm Dis. 2008;35:845-848. 2. Kent CK, et al. Clin Infect Dis. 2005;41:67-74.
3. Peters RP, et al. Sex Transm Dis. 2011;38:783-787. 4. Bernstein KT, et al. Clin Infect Dis.
2009;49:1793-1797.

10. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Extragenital GC and CT Diagnostics
 Sensitivity of culture < 50% to detect rectal and
pharyngeal GC vs > 90% sensitivity for NAATs (this can
vary by NAAT type)[1]
 The CDC recommends that NAATs be used to detect
these extragenital infections[2]
 Although none of the NAATs are FDA cleared to use with
extragenital specimens, most large laboratories have
established performance specifications to satisfy
compliance to Clinical Laboratory Improvement
Amendments
1. Ota KV, et al. Sex Transm Infect. 2009;85:182-186. 2. MMWR Recomm Rep. 2010;59:1-116.

11. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
GC and CT Screening Recommendations
Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e34.
Interval Site-Specific Screening
Chlamydia
Annually for
All women aged ≤ 25 yrs
All sexually active MSM
High-risk women* aged > 25 yrs
Every 3-6 mos for MSM
With multiple or anonymous partners
Use illicit drugs or who have partners who do
Anorectal: On the basis of report of receptive anal intercourse
Pharyngeal: Not recommended due to low prevalence
Gonorrhea
Annually for
All sexually active MSM
Every 3-6 mos for MSM
With multiple or anonymous partners
Use illicit drugs or who have partners who do
Targeted screening
High-risk women*
Anorectal: On the basis of report of receptive anal intercourse
Pharyngeal: If patient reports receptive oral sex
*Includes women with previous CT/GC infection, other STDs, new or multiple sex partners, inconsistent
condom use; those who engage in commercial sex work and drug use; certain demographic groups;
those living in communities with a high prevalence of disease.

12. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Trichomoniasis
 Indications for HIV+ women[1]
 At entry into care
 Subsequent screening performed at
least annually based on:
– Reported prevalence of
trichomonas vaginalis
– Effect of treatment at reducing
vaginal HIV shedding
– Potential complications of upper
genital–tract infections among
women who are left untreated
– Partners (among black women)[2]
 Diagnostics[2,3]
 Wet mount: sensitivity ~ 51% to
65% (time dependent)
 Culture: sensitivity 75% to 95%
 Rapid antigen test: sensitivity 82%
to 95%
 NAAT assay*: sensitivity 100%
– No FDA-approved NAATs for men;
some laboratories have verified the
performance characteristics of
NAATs through a validation
process for male urine specimens
or penile meatal swabs
1. MMWR Recomm Rep. 2010;59 ;1-116. 2. Sutton M, et al. Clin Infect Dis. 2007;45:1319-1326.
3. APHL. Issues in Brief: Laboratory Detection of Trichomonas. August 2013. www.aphl.org.
*FDA approved in 2011 for use with urine, endocervical, and vaginal swabs and Thin Prep Pap.

13. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Retesting to Detect Repeat Infections
 Reinfection with GC, CT, and trichomoniasis is common in
both men and women[1,2]
 All persons treated for GC, CT, and all women treated for
trichomoniasis should be retested in 3 mos because of
high reinfection rates regardless of whether their
partner(s) was/were treated[3]
1. Fung M, et al. Sex Transm Inf. 2007;83:304-309. 2. Hosenfeld CB, et al. Sex Transm Dis.
2009;36:478-489. 3. MMWR Recomm Rep. 2010;59:1-116.

14. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Syphilis: Serological Tests
1. Peeling RW, et al. Bull World Health Org. 2004;82:439-446. 2. CDC. Reverse sequence syphilis screening.
Common Patterns of Serological
Reactivity in Syphilis Patients[1]
Serological Tests For Syphilis[1,2]
Nontreponemal
Tests
Treponemal
Tests
Complement fixation
tests
 Wasserman
reaction
Flocculation tests
 RPR
 VDRL
 TRUST
 TPI
 FTA-Abs
 TPHA
 TPPA
 EIA
 WB and
pseudoblots
 Automated chemi-
luminescence
platforms
 Chromatographic
POC tests
 Microsphere
immunoassay
FTA-Abs
TPHA
VDRL/RPR
IgM
Untreated
Treated
100
80
60
40
20
2 4 6 8 10 12 2 10
20Time of
Reaction
Wks Yrs
Time Postinfection
Primary Secondary Latent
(asymptomatic)
TertiaryClinical Stages
of Syphilis
Primary lesion Secondary lesion
PatientsWhoTestPositive(%)

15. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Syphilis: Serological
Algorithms
Traditional Algorithm Reverse Sequence Algorithm
− +
CDC. Reverse sequence syphilis screening.
RPR/VDRL
No further
testing
Treponemal
test
No further
testing
RPR/VDRL
No further
testing
Confirmatory
treponemal test
Treponemal
immunoassay
(EIA/CIA)
+
−
− +

16. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Syphilis: Interpretation of
Reverse Sequence Algorithm
Slide courtesy of Barbara Detrick, JHH.

17. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Syphilis: Epidemiology
Syphilis and HIV
 The estimated proportion of
primary and secondary
syphilis cases attributable to
MSM increased from 7% in
2000 to 75% in 2012[1]
 In Maryland, 60% of primary
and secondary cases of
syphilis were among HIV+
MSM, and 30% of MSM
diagnosed with early syphilis
from 2010-2011 had been
diagnosed with syphilis in the
preceding 4 yrs[2,3]
1. www.cdc.gov. STD surveillance. 2012. 2. Data courtesy of Ravikiran Muvva, BCHD. 3. MMWR. 2013; 62:649-650.
25
20
15
10
5
0
16:1
8:1
4:1
2:1
1:1
100
80
60
40
20
0
Rate (per 100,000 Population) Rate Ratio (log scale)
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012
61.3
38.7
41.6
58.4
41.9
58.1
39.9
60.1
2009 2010 2011 2012
PrimaryandSecondary
CasesinMen(%)
Male
Female
Total
Male-to-female ratio
Yr
HIV
Negative/Unknown
HIV Positve
Yr

18. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Syphilis: Cost and Efficacy
 Every 3-mo screening among highly active MSM is very high-
yield and cost-efficient. Contact tracing is high-yield but costly.
Screening in jails also appeared to be cost-efficient[1,2]
 Mathematical models suggest that changes in behaviors and
condom use, particularly short-term ones (even long-term ones
if they are modest), would not affect syphilis rates, and that
frequent screening among very high-risk individuals is
probably what would have the most impact[3]
 Approximately 30% of high-risk MSM were not rescreened in
the 6 mos following therapy for syphilis[4]
1. Gray RT, et al. Sex Transm Dis. 2010;37:298-305. 2. Lewis FM, et al. J Public Health Manag Pract.
2011;17:513-521. 3. Gray RT, et al. Sex Transm Dis. 2011;38:1151-1158. 4. Marcus JL, et al. Sex
Transm Dis. 2011;38:24-29.

19. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Syphilis and HIV: Recommendations
 Routine serologic screening for syphilis is
recommended AT LEAST annually for sexually active
HIV-infected persons, with more frequent screening
(every 3-6 mos) in those with multiple partners, a
history of unprotected intercourse, a history of sex in
conjunction with illicit drug use, methamphetamine use,
or sexual partners who participate in such activities
Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e34.

20. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Screening for Herpes Simplex Viruses
 Routine screening for HSV is not recommended. Counseling infected
persons and their sex partners may help reduce the risk of HSV
sexual and perinatal transmission[1]
 Type-specific HSV serologic assays may be performed in the
following patients[2]
:
– Patients with recurrent genital symptoms or atypical symptoms in whom
HSV cultures/PCR have been negative
– Patients who have been given a clinical diagnosis of genital herpes
without laboratory confirmation
– Patients who have a partner with genital herpes
– Consider screening persons presenting for an STD evaluation, persons
HIV+, and MSM
1. Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e3. 2. MMWR Recomm Rep. 2010;59:1-116.

21. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
 Use glycoprotein G-based type-specific assays (gG1 and gG2)
– If gG2 is positive, patient has genital herpes
– If gG1 is positive, patient either has oral herpes or genital herpes
– Do NOT use crude antigen-based serological assays
– Do NOT use IgM serological assays
 REMEMBER:
– Antibodies may be negative in early primary infection
– The specificity of these tests is high but not perfect. As such, if the pretest
probability of having herpes is low, a positive test result has a high
likelihood of being a false positive
Screening Tests for Herpes Simplex Virus
Wald A, et al. Clin Infect Dis. 2002;35:S173-S182.

22. Management
Gonorrhea Therapy and
Human Papillomavirus Prevention

23. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Gonorrhea Drug Resistance Timeline
Unemo M, et al. Ann N Y Acad Sci. 2011;1230:E19-E28.
Protargol
1897
Protargol
no longer
recommended
1938
Sulphonamide
resistance wide
spread
1944-45
1936
Sulphonamides
1943
Penicillin
Erythromycin
1952
Spectinomycin
1961
1962
Tetracycline
1958
Penicillin and
streptomycin
clinical resistance
first reported
1949
Streptomycin
and
chloramphenicol
1977
Erythromycin
resistance wide
spread
β-lactamase
plasmids
first reported
(high-level
penicillin
resistance)
1976
Ceftriaxone
1980
Cefixime
1983
1983
Azithromycin
1987
Spectinomycin
resistance
reported to
rapidly emerge
when widely
used
1989
Penicillin
no longer
recommended
1985
Tetracycline
high-level
resistance
reported
Tetracycline
no longer
recommended
1986
1993
Fluoroquinolones,
cefixime and
ceftriaxone
recommended
Ceftriaxone
recommended
(ciprofloxacin
alternative)
1989
Chromosomal
penicillin
resistance
elucidated
1985
Fluoroquinolone
resistance first
reported in USA
(Hawaii) –
already a
problem in Asia
1991
Cefixime out
of production
2002
Fluoroquinolones
no longer
recommended
2007
Cefixime clinical
failure verified
beyond Japan
(in Europe)
2007
2021?
Untreatable
gonorrhea?
2011
First high-level
ceftriaxone
resistant strain fully
characterized
Super Bug Status!!
2001
Cefixime
decreased
susceptibility in
Hawaii, USA
2007
Azithromycin
no
longer
recommended
2008
Cefixime
available
again
1999
Azithromycin
resistance
first
reported

24. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Mechanisms of Resistance to
Cephalosporins
 Combined effects of several
chromosomal mutations:
– PenA (PBP2)
– Results in 100× increased MIC to
cefixime
– Results in 20× increased MIC to
ceftriaxone
– Acquired via horizontal transfer
from oral commensal bacteria (N
sicca, N perflava, N cinerea, and/or
N flavescens)
– MtrR (MTRCDE-encoded pump
repressor)
– MtrR mutations result in
overexpression of an efflux pump
– PenB (PorB1b)
– Decrease the influx of the antibiotic
into the periplasm
Bolan GA, et al. N Engl J Med. 2012;366:485-487.

25. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
GC Cephalosporin Susceptibility: United
States and the World
 Although the MIC
breakpoints for resistance
to cephalosporin have not
been defined, the CLSI
defines susceptibility to
cefixime and ceftriaxone
as MICs of 0.25 μg/mL or
below and 0.125 μg/mL or
below, respectively[1]
1. Bolan GA, et al. N Engl J Med. 2012;366:485-487. 2. Unemo M, et al. Euro Surveill. 2010;15:19721. 3. Unemo M, et al.
Euro Surveill. 2011;16:19792. 4. Unemo M, et al. Antimicrob Agents Chemother. 2012;56:1273-1280.
[2]
[3]
[4]
5
4
3
2
1
0
2005
2006
2009
2010
2011
MSM
West
Midwest
Northeast and
South
Men who report having
sex exclusively with
women
IsolatesWithElevated
MICsofCefixime(%)
Percentage of Isolates in Which MICs of Cefixime
Were ≥ 0.25 µg/mL, 2005-2011[1]

26. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
GC Macrolide Resistance
 133 GISP isolates with reduced susceptibility to
azithromycin (at MIC ≥ 2 μg/mL) have been reported in
the United States since 2005, including 7 (0.5% of GISP
isolates) in 2012[1,2]
 The first strain with high-level resistance to azithromycin
(MIC ≥ 512 μg/mL) identified in the United States was
detected in Hawaii in 2011, and several additional
strains have now been detected in Hawaii and
California[2]
1. MMWR Recomm Rep. 2010;59:1-116. 2. Katz AR, et al. Clin Infect Dis. 2012;54:841-843.

27. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Updated CDC GC Treatment
Recommendations
 Firstline
– Ceftriaxone 250 mg IM x 1 + azithromycin 1 g PO × 1 or
doxycycline 100 mg PO BID × 7 days
– Azithromycin is preferred over doxycycline, but both are acceptable
– Use dual therapy even if C trachomatis is ruled out
 Alternate
– Cefixime 400 mg PO x 1 + azithromycin 1 g PO × 1 or doxycycline
100 mg PO BID × 7 days
– Azithromycin 2 g PO × 1 (single therapy, single dose)
– Azithromycin 2 g PO × 1 is the only regimen currently available to treat
a patient who has an allergy to cephalosporins
CDC. Morb Mortal Wkly Rep. 2012;61:590-594.

28. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Treatment Failure With Alternate Regimens
 Culture relevant clinical sites and perform antimicrobial
susceptibility testing using disk diffusion, E-test, or agar
dilution
 Treat with intramuscular ceftriaxone 250 mg +
azithromycin 2 g orally as a single dose
 Evaluate sex partners from the preceding 60 days with
culture from all exposed sites and treat with above
enhanced regimen
 The laboratory should retain the isolate for possible
further testing
CDC. Morb Mortal Wkly Rep. 2012;61:590-594.

29. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
What About Patients With Penicillin or
Cephalosporin Allergies?
 The cross-reactivity between penicillins and
cephalosporins has been found to be low (< 2.5%)
– The risk is highest with first-generation cephalosporins
– The risk of penicillin cross-reactivity between most second-
generation and all third- and fourth-generation
cephalosporins is negligible
 If severe allergy to penicillin or cephalosporins, treat with
azithromycin 2 g PO × 1
 Oral PID treatment in that setting is more complicated
Park MA, et al. Int Arch Allergy Immunol. 2010;153:268-273. Novalbos A, et al. Clin Exp Allergy.
2001;31:438-443.

30. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
Future Antimicrobial Options
 Recent randomized trial of:
– Injectable gentamicin (5 mg/kg) + oral azithromycin (2 g)
– 100% effectiveness
– Oral gemifloxacin (320 mg) + oral azithromycin (2 g)
– 99.5% effectiveness
 Many trial participants reported adverse effects from the
drugs, mostly gastrointestinal issues
Kirkcaldy RD. Sex Transm Infect. 2013;89:A14-A15.

31. clinicaloptions.com
24th Annual CCO HIV and Hepatitis C Symposium
HPV: Anal Pap and HPV Vaccination
 Anal Pap screening recommendations
 Recommended groups
– MSM
– Women with history of receptive anal
intercourse or abnormal cervical Pap
test results
– All HIV+ persons with genital warts
(weak recommendation, moderate
quality evidence)[1]
 If anal cytologic screening (anal Pap
smears) is performed and abnormal:
– High-resolution anoscopy should be
performed with biopsy of abnormal
areas
– Appropriate therapy based on biopsy
results[1]
 HPV vaccination recommendations
 ACIP recommends vaccination for all
HIV-infected males (quadrivalent
vaccine only) and females in a 3-dose
series at 11 or 12 yrs of age and for
those 13-26 yrs of age if not previously
vaccinated[1]
– Efficacy data in HIV+ patients lacking
– 1 small trial in HIV+ boys and girls found
the vaccine safe and immunogenic as
did a study in HIV-infected men[2,3]
1. Aberg JA, et al. Clin Infect Dis. 2014;58:e1-e34. 2. Levin MJ, et al. J Acquir Immune Defic Syndr. 2010;55:197-204.
3. Wilkin T, et al. J Infect Dis. 2010;202:1246-1253.