STI Update

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STI Update

• Peter A. Leone,MD
• Associate Professor of Medicine
• University of North Carolina
• Medical Director
• North Carolina HIV/STD Prevention and Care Branch

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North Carolina HIV Disease Reports
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North Carolina HIV

• 32,000 living with HIV
• 18,000 aware of HIV infection
• 12,000-13,000 in care
• 30-40 unaware of HIV status

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Awareness of Serostatus Among People with HIV and
Estimates of Transmission
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Identification of HIV Status to Reduce
Transmission

• Goal of new CDC recommendations to increase
  number who know HIV status
• People do not perceive risk
• Clinicians do not offer test
• Stigma of identified risk and of testing
• Knowing HIV status can reduce transmission by
  - Behavior change
• - HAART reducing viral load

MMWR 551-7, 2006 Inungu J. AIDS atient Care
STDs 16293, 2002
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Knowledge of HIV Infection and Behaviour
Reduction in unprotected anal or vaginal
intercourse with HIV Negative partners - HIV
positive aware vs HIV positive unaware 68 (95
CI 5976)
Source Marks G, et al. Meta-analysis of high
risk sexual behavior, aware vs unaware. JAIDS.
2005
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Source of HIV tests and Positive Tests

• 38-44 of adults 18-64 yrs. have been tested
• 16-22 million aged 18-64 yrs. tested/yr in U.S.
• HIV
  Tests HIV Tests
• Private MD/HMO 44
  17
• Hospital/ED/Outpt. 22
  27
• Public clinics 9
  21
• HIV CT 5
  9
• Drug treatment 0.7
  2
• Correctional facility 0.6
  5
• STD clinics 0.1
  6

National Health Interview Survey,2002 Suppl to
HIV/AIDS surveillance,2000-2003
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New CDC Recommendations for Screening for HIV
infection

• In all health care settings, screening for HIV
  infection should be routinely performed for all
  patients age 13-64
• Providers should initiate screening unless HIV
  prevalence has been documented to be lt0.1.
• All patients initiating treatment for TB should
  be routinely screened for HIV infection
• All patients seeking treatment for STDs,
  including all patients attending STD clinics,
  should be routinely screened for HIV during each
  visit for a new complaint, regardless of patient
  specific behavioral risks for HIV infection.

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Further Modification to Routinize HIV testing
in Medical Care Settings

• "Testing for HIV may be offered as part of
  routine laboratory testing panels using a general
  consent which is obtained from the patient for
  treatment and routine laboratory testing,so long
  as the patient is notified that they are being
  tested for HIV and given the opportunity to
  refuse testing."

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Changes to NC Administrative CodeNov. 1, 2007

• Providers and Laboratories to report HIV/AIDS
  from 7 days to 24 hrs
• HIV testing can be a part of a panel of tests
  without a standalone written consent just for HIV
  testing as long as the consent for testing
  specifies that HIV testing is included.

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Changes to NC Administrative CodeNov. 1, 2007

• Opt-out HIV screening in medical settings and for
  prenatal and STD visits
• Pretest counseling not required
• Post-test counseling required only for positives
• HIV tests at first prenatal visit and 3rd
  trimester
• Mandatory HIV test at LD for all women for whom
  HIV status is unknown and in infant if test not
  obtained from mother

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General Consent Form

• I hereby voluntarily consent to medical and/or
  dental examinations, treatments and procedures
  which are deemed necessary in the opinion of my
  physician and health care providers, including
  HIV tests, laboratory tests and x-rays. I
  understand that my medical information is
  strictly confidential and is protected by North
  Carolina General Statute 130A-143 and no
  guarantees or warrantees have been made to me
  concerning the results of the examinations,
  treatments or procedures. My signature
  acknowledges that I have been given the
  opportunity to ask questions about this consent
  form and the opportunity to refuse services.
• Client Signature _____________
  Date_____________

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• HIV Required Reporting in NC
• Confirmed HIV infection is defined as
• - a positive virus culture
• - repeatedly reactive EIA antibody test
  confirmed by WB or indirect immunofluorescent
  antibody test
• - positive polymerase chain reaction (PCR)
  test or other confirmed testing method approved
  by the Director of the State Public Health
  Laboratory

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HIV/STD Rule Changes (STD)

• http//www.epi.state.nc.us/epi/hiv/
• Branch Overview
• Current Initiatives

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UNC Hospitals Rules Changes

• UNC Health Care System has required a written
  consent from patients for HIV tests. The HIV
  testing rules have been revised and, as a result,
  after January 1, 2008, a separate written consent
  for HIV testing will not be required. Our
  General Consent for Treatment contains a consent
  for routine laboratory testing that encompasses
  HIV testing.

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Rules Changes

• NOTE Patients must still be notified in advance
  that the test will be performed and, with
  exceptions below, patients must still consent to
  the testing. This notification and consent may be
  done orally, but the physician must document in
  the patients medical record.
• Pre-test counseling is no longer required for HIV
  testing.

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Window Periods for HIV Tests
Stekler J. et al CID 2007
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HIV viremia during early infection
Peak viremia 106-108 gEq/mL
HIV RNA (plasma)
Ramp-up viremia DT 21.5 hrs
HIV Antibody
HIV p24 Ag
p24 Ag EIA -
Viral set-point 102 -105 gEq/mL
HIV MP-NAT -
1st gen
2nd gen
HIV ID-NAT -
4th gen
3rd gen
blip viremia
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16
22
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3rd Generation HIV assays

• Moving the window to the left
• Increase in ELISA and WB or WB/-
• Think AHI but recognize may have false positive

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Non-specific Mononucleosis-like Signs and Symptoms

• Fever
• Rash
• Oral ulcer
• Weight loss
• Loss of appetite
• Headache
• Fatigue

• Adenopathy
• Sore throat/ pharyngitis
• Muscle and/or joint pain
• Diarrhea
• GI upset/nausea/
• vomiting

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Common Signs Symptoms
Study of 160 patients with primary HIV infection
in 3 countries
of patients
Vanhems P et al. AIDS 2000 140375-0381. 
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Role of Rapid Antibody Testing

• Makes testing feasible in non-traditional
  settings
• Highly effective for outreach situations (needle
  exchange, bathhouse testing, street-corner
  outreach)
• Increases receipt of positive HIV test results
• Where HIV results notification (PCRS) not in
  place
• Might increase requests for HIV testing
• Is not preferred in many established testing
  settings
• Cost 2-3x ELISA Ab tests
• May defer resource allocation to HIV negatives
• May miss AHI

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PCR Testing of Pooled Sera to Identify Acute HIV
Infection (seronegative, PCR positive)
Source ISSTDR, 2007
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Typical Course of Primary HIV
HIV RNA
HIV RNA
HIV-1 Antibodies
Ab
P24
Exposure
Symptoms
10
0
14
21
28
35
3
Days
Source Hecht. Primary HIV.
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If you have an STD, Get Tested for HIV. Early
Detection is Best! Learn to Recognize IT. Tell a
Friend. Acute HIV is Easily Misdiagnosed. IT CAN
BE MISTAKEN FOR COMMON ILLNESSES
Common Symptoms of Acute HIV High Fever
Rash Fatigue Swollen Glands Sore Throat
Nausea/Vomiting Night Sweats Symptoms usually
appear about 2 weeks after exposure What Puts You
At Risk? Unprotected Sex Sharing Needles The
Acute HIV Program 919-966-8533

• If you suspect you may have Acute HIV, get tested
  at your Local Health Department or at your
  doctors office.
• FREE Screening for acute HIV is done on all HIV
  tests done through the NC Health Departments
• Screening for acute HIV can be done at your
  doctors office ask for an HIV RNA test in
  addition to the standard HIV antibody test.

SPREAD THE WORD - NOT HIV
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Acute HIV and North CarolinaSTAT
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Wesolowski et al, PLoS 2008
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Discordant results

• 167,371 rapid HIV ELISA
• 2589 (1.6) HIV
• 2417 (93) WB/IFA
• 172 (7) WB/IFA - or /-
• 89/182 (52) repeat confirmatory test
• 17 (19) were HIV (3 WB /- and NAAT)
• 72/89 (81) were uninfected (12 repeat WB /-)
• Discordants
• 50 repeat for which 20 were HIV (3 AHI)

Wesolowski et al, PLoS 2008
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Discordant results

• EIA / ELISA require confirmatory test

WB
WB WB or /-
NAAT
NAAT
NAAT -
NAAT/-
AHI
Repeat test Probable -
HIV
AHI
HIV-
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HIV Testing Goals

• Universal testing of individuals 13-64 yr
• Opt-out testing in STD/ Prenatal/Prison settings
• Allow uncoupling of pre- and post-test counseling
  from HIV testing itself
• Think and test for AHI ( RNA) with mono-like
  illness in sexually active adult. Fast Track

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GC
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Gonococcal Isolate Surveillance Project (GISP)
Percent of Neisseria gonorrhoeae isolates with
resistance or intermediate resistance to
ciprofloxacin, 19902004
Note Resistant isolates have ciprofloxacin 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.
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Gonococcal Isolate Surveillance Project (GISP)
Percent of Neisseria gonorrhoeae isolates with
resistance to ciprofloxacin by sexual behavior,
20012004
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Gonorrhea

• Do not use quinolones (cipro, oflox, levo)
  http//www.cdc.gov/std/gisp

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Previous Recommendations2006 NC STD Treatment
GuidelinesUncomplicated Gonorrhea

• Cefpodoxime 400 mg PO x 1
• or
• Ceftriaxone 125mg IM
• Alternatives Gentimicin 240 mg IM ( not for oral
  pharyngeal)- do test of cure
• Quinolones Do test of cure
  
• Ciprofloxacin 500mg PO
• or
• Ofloxacin 400mg PO
• or
• Levofloxacin 250mg PO
• Azithromycin 2.0 g PO (
  expensive, nausea and vomiting)
• Add co-treatment for Ct if not treating with
  Azithromycin
• Plus, Azithromycin 1g PO or Doxycycline 100mg po
  BID x 7d

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2008 NC STD Treatment GuidelinesUncomplicated
Gonorrhea

• Cefixime 400 mg PO x 1
• or
• Ceftriaxone 125mg IM
• Alternatives Gentimicin 240 mg IM ( not for oral
  pharyngeal)- do test of cure
• Quinolones Do test of cure
  
• Ciprofloxacin 500mg PO
• or
• Ofloxacin 400mg PO
• or
• Levofloxacin 250mg PO
• Azithromycin 2.0 g PO (
  expensive, nausea and vomiting)
• Add co-treatment for Ct if not treating with
  Azithromycin
• Plus, Azithromycin 1g PO or Doxycycline 100mg po
  BID x 7d

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2006 CDC STD Treatment GuidelinesUncomplicated
Gonorrhea

• Alternatives
• Spectinomycin 2g IM
• Oral Alternatives
• Cefpodoxime (Vantin) 400mg PO single dose OR
• Cefuroxime (Ceftin) 500mg PO single dose

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Fung et al. National STD Prevention Conference.
2006
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Urethritis Management

• 2006 CDC STD Guidelines
• If Chlamydia or Gonorrhea positive, some experts
  suggest repeat Chlamydia or Gonorrhea Testing in
  About 3 Months

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Treponema pallidum
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The Course of Untreated Syphilis
6 weeks to 6 months
Many years to a lifetime
Approx. 18 months
Infection
Primary (Chancre)
Secondary (Rash)
Latent Syphilis (No signs of disease)
Tertiary
Benign gummatous Cardio-vascular
syphilis Neurosyphilis
Incubation period 9 90 days
Many years to a lifetime Late Syphilis
1-2 years Early Syphilis
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Primary and Secondary Syphilis United States
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Diagnosis of Syphilis

• Darkfield microscopy
• Direct immunofluorescence
• Polymerase chain reaction (PCR)
• Serology
• Nonspecific (Cardiolipin-based)
• Specific (Treponemal)

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Serological Tests for Syphilis

• Non-treponemal (reagin) tests
• Complement Fixation Test
• Wasserman reaction
• Flocculation Reactions
• Rapid plasma reagin (RPR) test
• VDRL
• TRUST
• Treponemal (specific) tests
• TPI
• FTA-ABS
• TPHA
• TPPA
• ELISA (EIA)
• Automated chemiluminescence
  platforms
• Current Chromatographic (POC) Tests

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Principle of the Rapid Plasma Reagin Test
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RPR Rotator
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Qualitative RPR Test
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Quantitative RPR Test
End-Point Titer (164)
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Reactivity of Non-treponemal Serological Tests by
Stage of Syphilis and Influence of Successful
Treatment
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Serologic Tests for Syphilis
Test Sensitivity by stage of untreated
syphilis Specificity Primary
Secondary Latent Late VDRL 74-87
100 88-100 37-94 96-99 RPR
77-100 100 95-100 73
93-99 TRUST 77-86 100
95-100 98-99 MHA-TP 69-90 100
97-100 94 98-100 FTA-ABS 70-100
100 97-100 98-100
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Principle of FTA-ABS Test
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Fluorescent Treponemal Antibody Test
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Principle of Treponema pallidum
Haemagglutination Assay
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Treponema pallidum Haemagglutination Assay
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Treponema pallidum Passive Particle
Agglutination Assay (TPPA)
Interpretation of Results Positive Control
Dilution()()()(/-)(-)(-)
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ELISA Test
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DiaSorin Liaison Treponemal Chemiluminescence
Assay
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DiaSorin Liaison Treponemal Chemiluminescence
Assay Principle of Test
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Reactivity of Treponemal Serological Tests by
Stage of Syphilis and Influence of Successful
Treatment
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Use of Treponemal and Non-treponemal Tests to
Monitor Impact of Specific Interventions for
Syphilis Among STD Patients
Treponemal
15
Seropositive
10
Non-treponemal
5
0
5
2
1
4
Time (Years)
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Interpretation of Serological Tests for Syphilis

• RPRve, FTA-ABS-ve
• False positive RPR screening test
• RPRve, FTA-ABSve
• Untreated syphilis
• Previously treated late syphilis
• RPR-ve, FTA-ABSve
• Very early untreated syphilis
• Previously treated early syphilis
• RPR-ve, FTA-ABS-ve
• Not syphilis
• Incubating syphilis
• Very late syphilis
• Syphilis with concomitant HIV infection

Note These possible interpretations do not
necessarily have equal weight
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Syphilis Serology Conventional Wisdom

• Screen with a Non-treponemal test (eg. an RPR,
  VDRL Test)
• (ie. an inexpensive test with high
  sensitivity, but which may lack some specificity)
• Confirm with a Treponemal test (eg. FTA-Abs,
  TP-PA, etc.)
• (ie. a relatively expensive test which is
  highly specific, but which may lack some
  sensitivity)

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Changing Times in Syphilis Serology

• Prevalence of syphilis is extremely low in many
  industrialized countries
• Labor costs have increased
• Introduction of treponemal tests which can be
  fully automated

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Syphilis Serology An Alternative Approach in
Low Prevalence Settings

• Screen with a Treponemal test (eg. TP-PA, EIA,
  Automated or POC test.)
• Confirm with a Non-treponemal test (eg. an RPR,
  VDRL Test)
• It is important that all specimens that test
  positive with the initial treponemal test be
  retested with a non-treponemal test to give a
  better indication of disease that requires
  therapy.

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What should we do with discordant treponemal/
non-treponemal results?

• For the first time we will detect treponemal
  Ab- positive, non-treponemal Ab-negative
  specimens during screening.
• This situation has resulted in considerable
  confusion among both laboratorians and clinicians

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Suggested Algorithm for Serological Screening
for Syphilis
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Syphilis Serology The Conventional Wisdom
Should Prevail in High Prevalence Settings

• It is more important to differentiate between
  active and previously- treated disease, otherwise
  overtreatment rates would be unacceptably high
• Labor costs largely remain low in comparison to
  the cost of test kits
• The capital and maintenance costs of automated
  systems may be prohibitive

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Conclusions

• Treponemal screening alone has profound
  implications for both treatment of individuals
  and also disease control activities.
• There are clearly problems associated with
  screening with treponemal tests and reporting
  these results without also performing and
  reporting a confirmatory non-treponemal test
  result.
• CDC is planning a consultation, with APHL, later
  this year to formulate recommendations regarding
  laboratory diagnostic testing for STDs including
  serological testing for syphilis. These
  guidelines will act as a companion document to
  the CDC STD Treatment Guidelines.

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Protocol for Tp

• Tp and RPR untreated syphilis unless R/O by
  Rx history
• Tp and gt4x titer RPR new infection
• Tp but RPR
• Hx of previous Rx no further F/U
• No Hx of Rx
• Obtain different 2nd Tp
• If 2nd Tp then discuss with patient

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2nd Tp Test

• Obtain different 2nd Tp (probably Tp WB)
• If 2nd Tp then discuss with patient
• Unlikely infectious treat for
  LLS
• If 2nd Tp then discuss with patient
• No further F/U

Atkas et alInt J STD AIDS 2007 MMWR Aug. 15, 2008
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2006 CDC STD Treatment Guidelines Syphilis and
PCN Allergy

• Primary, Secondary, and Early Latent
• Doxy 100mg po bid or tetracycline 500mg qid x 2
  wks OR
• Azithromycin 2 G po single dose OR
• Ceftriaxone 1 g IM/IV daily x 8-10d
• Late Latent Syphilis or Unknown Duration
• Doxy 100mg po bid or tetracycline 500mg qid x 4
  wks
• Ceftriaxone?
• Neurosyphilis
• Ceftriaxone 2 g IM/IV daily for 10-14d as an
  alternative in neurosyphilis

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Treatment of Partners, Suspect and Associates

• Screen
• If lt 90 Days Rx if or
• If gt 90 Days Rx if
• No Rx if -

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Policy for Billing

• 10. "All local health departments will offer
  HIV and STD services at no cost to the client
  regardless of county of residence.
• Exceptions include
• a) asymptomatic clients who request screening
  for non-reportable STDs (e.g. herpes serology,
  Hep C)
• b) clients who receive follow-up treatment of
  warts after the diagnosis is established
• c) clients who request testing not offered by the
  state.
• These clients may be billed for testing and
  screening according to local billing policy".
  Thus, those asymptomatic males who request and
  are willing to pay for a chlamydia test can be
  billed for the chlamydia test. Your protocol
  should include a stat gram stain for symptomatic
  males to rule out GC. If the gram stain is
  negative, the client should be treated in
  accordance with the NGU protocol whether or not
  the chlamydia test is done

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HSV Diagnosis

• Provided by the State lab
• Culture
• Not Provided by the State Lab
• PCR (Not FDA approved for genital site)
• Western blot
• FDA Approved IgG type specific tests include
• HerpeSelect ELISA HSV-2 or HSV-1
• HerpeSelect Immunoblot for HSV-2 and HSV-1
• Biokit HSV-2 Rapid Test
• SureVue HSV-2

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When should type-specific serology be performed?

• Recurrent genital symptoms or atypical symptoms
  with negative HSV cultures
• Clinical diagnosis of HSV without lab
  confirmation
• Partner with genital herpes
• ? patients with multiple sexual partners, HIV
  patients and MSM

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Genital Herpes Episodic Treatment

• HIV-negative
• Acyclovir 400 mg TID or 800 mg BID x 5d or 800mg
  TID x 2d
• Famciclovir 125 mg BID x 5d or 1000mg BID x 1d
• Valacyclovir 500 mg BID x 3d or 1 g qd x 5 d
• HIV-positive
• Acyclovir 400 mg TID x 5-10 d
• Famciclovir 500 mg bid x 5-10 d
• Valacyclovir 1 G bid x 5-10 d

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Genital Herpes Suppressive Therapy

• HIV-
• Acyclovir 400mg po BID
• Famciclovir 250mg po BID
• Valacyclovir 500mg po qd
• Valacyclovir 1g po qd
• HIV
• Acyclovir 400-800mg po BID-TID
• Famciclovir 500mg po BID
• Valacyclovir 500mg po BID

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HSV and Pregnancy

• To date, no increased risk of birth defects in
  women treated with acyclovir during 1st trimester
• More limited data for valacyclovir and
  famciclovir
• Many specialists recommend HSV suppression during
  third trimester in order to prevent C-section