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

North Carolina HIV Disease Reports North Carolina HIV Disease Reports

North Carolina HIV • • ~32, 000 living with HIV ~ 18, 000 aware 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

Awareness of Serostatus Among People with HIV and Estimates of Transmission ~25% unaware of Awareness of Serostatus Among People with HIV and Estimates of Transmission ~25% unaware of infection ~55% of new infections ~75% aware of infection ~45% of new infections PLWHA New infections each year

Identification of HIV Status to Reduce Transmission • Goal of new CDC recommendations to 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 55: 1 -7, 2006 Inungu J. AIDS atient Care STDs 16: 293, 2002

Knowledge of HIV Infection and Behaviour Reduction in unprotected anal or vaginal intercourse with 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: 59%– 76%) Source: Marks G, et al. Meta-analysis of high risk sexual behavior, aware vs unaware. JAIDS. 2005

Source of HIV tests and Positive Tests • 38 -44% of adults 18 -64 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 Hospital/ED/Outpt. Public clinics HIV C&T Drug treatment Correctional facility STD clinics 44% 22% 9% 5% 0. 7% 0. 6% 0. 1% National Health Interview Survey, 2002; Suppl; to HIV/AIDS surveillance, 2000 -2003 17% 21% 9% 2% 5% 6%

New CDC Recommendations for Screening for HIV infection: • In all health care settings, 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 <0. 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.

Further Modification to “Routinize” HIV testing in Medical Care Settings 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. "

Changes to NC Administrative Code Nov. 1, 2007 • Providers and Laboratories to report Changes to NC Administrative Code Nov. 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.

Changes to NC Administrative Code Nov. 1, 2007 • Opt-out HIV screening in medical Changes to NC Administrative Code Nov. 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 3 rd trimester • Mandatory HIV test at L&D for all women for whom HIV status is unknown and in infant if test not obtained from mother

General Consent Form I hereby voluntarily consent to medical and/or dental examinations, treatments and 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 130 A-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_______

HIV Required Reporting in NC Confirmed HIV infection is defined as: - a positive 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

HIV/STD Rule Changes (STD) • http: //www. epi. state. nc. us/epi/hiv/ • Branch Overview HIV/STD Rule Changes (STD) • http: //www. epi. state. nc. us/epi/hiv/ • Branch Overview • Current Initiatives

UNC Hospitals Rules Changes Ø UNC Health Care System has required a written consent UNC Hospitals Rules Changes Ø 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.

Rules Changes Ø NOTE: Patients must still be notified in advance that the test Rules Changes Ø 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 patient’s medical record. Ø Pre-test counseling is no longer required for HIV testing.

Window Periods for HIV Tests Stekler J. et al CID 2007 Window Periods for HIV Tests Stekler J. et al CID 2007

HIV viremia during early infection Peak viremia: 106 -108 g. Eq/m. L HIV RNA HIV viremia during early infection Peak viremia: 106 -108 g. Eq/m. L HIV RNA (plasma) Ramp-up viremia DT = 21. 5 hrs HIV Antibody HIV p 24 Ag EIA HIV MP-NAT HIV ID-NAT - “blip” viremia 0 11 10 4 th 2 nd gen 3 rd gen 16 20 Viral set-point: 102 -105 g. Eq/m. L 1 st gen 22 30 40 50 60 70 80 90 100

3 rd Generation HIV assays • Moving the window to the “left” • Increase 3 rd Generation HIV assays • Moving the window to the “left” • Increase in ELISA + and WB – or WB+/ • Think AHI but recognize may have false positive

Non-specific Mononucleosis-like Signs and Symptoms n Fever n Adenopathy n Rash n Sore throat/ Non-specific Mononucleosis-like Signs and Symptoms n Fever n Adenopathy n Rash n Sore throat/ pharyngitis n Muscle and/or joint n Weight loss pain n Loss of appetite n Diarrhea n Headache n GI upset/nausea/ n Fatigue vomiting n Oral ulcer

Common Signs & Symptoms Study of 160 patients with primary HIV infection in 3 Common Signs & Symptoms Study of 160 patients with primary HIV infection in 3 countries % of patients Vanhems P et al. AIDS 2000; 14: 0375 -0381.

Role of Rapid Antibody Testing • Makes testing feasible in non-traditional settings – Highly 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 -3 x ELISA Ab tests • May defer resource allocation to HIV negatives • May miss AHI

PCR Testing of Pooled Sera to Identify Acute HIV Infection (seronegative, PCR positive) Source: PCR Testing of Pooled Sera to Identify Acute HIV Infection (seronegative, PCR positive) Source: ISSTDR, 2007

Typical Course of Primary HIV RNA 100, 000 HIV RNA 10, 000 100 Ab Typical Course of Primary HIV RNA 100, 000 HIV RNA 10, 000 100 Ab P 24 + + _ Exposure Symptoms 10 0 Source: Hecht. Primary HIV. 3 14 21 Days 28 35 HIV-1 Antibodies 1 mil

If you have an STD, Get Tested for HIV. Early Detection is Best! Learn 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 doctor’s 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 doctor’s office – ask for an HIV RNA test in addition to the standard HIV antibody test.

Acute HIV and North Carolina STAT Acute HIV and North Carolina STAT

Wesolowski et al, PLo. S 2008 Wesolowski et al, PLo. S 2008

Discordant results • • 167, 371 rapid HIV ELISA 2589 (1. 6%) HIV + 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, PLo. S 2008

Discordant results • EIA / ELISA + require confirmatory test WB + WB – Discordant results • EIA / ELISA + require confirmatory test WB + WB – NAAT + WB or +/- NAAT ++ NAAT+/- HIV+ AHI HIV- Repeat test Probable - AHI

HIV Testing Goals • Universal testing of individuals 13 -64 yr • Opt-out testing 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

GC GC

Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990– 2004 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.

Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001– 2004

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

Previous Recommendations 2006 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefpodoxime 400 mg PO x Previous Recommendations 2006 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefpodoxime 400 mg PO x 1 or Ceftriaxone 125 mg IM Alternatives: Gentimicin 240 mg IM ( not for oral pharyngeal)- do test of cure Quinolones: Do test of cure Ciprofloxacin 500 mg PO or Ofloxacin 400 mg PO or Levofloxacin 250 mg PO Azithromycin 2. 0 g PO ( expensive, nausea and vomiting) Add co-treatment for Ct if not treating with Azithromycin Plus, Azithromycin 1 g PO or Doxycycline 100 mg po BID x 7 d

2008 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefixime 400 mg PO x 1 or 2008 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefixime 400 mg PO x 1 or Ceftriaxone 125 mg IM Alternatives: Gentimicin 240 mg IM ( not for oral pharyngeal)- do test of cure Quinolones: Do test of cure Ciprofloxacin 500 mg PO or Ofloxacin 400 mg PO or Levofloxacin 250 mg PO Azithromycin 2. 0 g PO ( expensive, nausea and vomiting) Add co-treatment for Ct if not treating with Azithromycin Plus, Azithromycin 1 g PO or Doxycycline 100 mg po BID x 7 d

2006 CDC STD Treatment Guidelines Uncomplicated Gonorrhea Alternatives: • Spectinomycin 2 g IM Oral 2006 CDC STD Treatment Guidelines Uncomplicated Gonorrhea Alternatives: • Spectinomycin 2 g IM Oral Alternatives: • Cefpodoxime (Vantin®) 400 mg PO single dose OR • Cefuroxime (Ceftin®) 500 mg PO single dose

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

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

Treponema pallidum Treponema pallidum

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

Primary and Secondary Syphilis – United States Primary and Secondary Syphilis – United States

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

Serological Tests for Syphilis Non-treponemal (reagin) tests Complement Fixation Test Wasserman reaction Flocculation Reactions 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

Principle of the Rapid Plasma Reagin Test Principle of the Rapid Plasma Reagin Test

RPR Rotator RPR Rotator

Qualitative RPR Test Qualitative RPR Test

Quantitative RPR Test End-Point Titer (1: 64) Quantitative RPR Test End-Point Titer (1: 64)

Reactivity of Non-treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment Reactivity of Non-treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment

Serologic Tests for Syphilis Test Sensitivity by stage of untreated syphilis Primary Secondary Latent Serologic Tests for Syphilis Test Sensitivity by stage of untreated syphilis Primary Secondary Latent Late Specificity VDRL 74 -87% 88 -100% 37 -94% 96 -99% RPR 77 -100% 95 -100% 73% 93 -99% TRUST 77 -86% 100% 95 -100% 98 -99% MHA-TP 69 -90% 100% 97 -100% FTA-ABS 70 -100% 97 -100% 94% 98 -100%

Principle of FTA-ABS Test Principle of FTA-ABS Test

Fluorescent Treponemal Antibody Test Fluorescent Treponemal Antibody Test

Principle of Treponema pallidum Haemagglutination Assay Principle of Treponema pallidum Haemagglutination Assay

Treponema pallidum Haemagglutination Assay Treponema pallidum Haemagglutination Assay

Treponema pallidum Passive Particle Agglutination Assay (TPPA) Interpretation of Results Positive Control Dilution(++)(+)(+)(+/-)(-)(-) Treponema pallidum Passive Particle Agglutination Assay (TPPA) Interpretation of Results Positive Control Dilution(++)(+)(+)(+/-)(-)(-)

ELISA Test ELISA Test

Dia. Sorin Liaison Treponemal Chemiluminescence Assay Dia. Sorin Liaison Treponemal Chemiluminescence Assay

Dia. Sorin Liaison Treponemal Chemiluminescence Assay – Principle of Test Dia. Sorin Liaison Treponemal Chemiluminescence Assay – Principle of Test

Reactivity of Treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment Reactivity of Treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment

% Seropositive Use of Treponemal and Non-treponemal Tests to Monitor Impact of Specific Interventions % Seropositive Use of Treponemal and Non-treponemal Tests to Monitor Impact of Specific Interventions for Syphilis Among STD Patients Treponemal 15 10 Non-treponemal 5 0 1 2 Time (Years) 4 5

Interpretation of Serological Tests for Syphilis • RPR+ve, FTA-ABS-ve False positive RPR screening test Interpretation of Serological Tests for Syphilis • RPR+ve, FTA-ABS-ve False positive RPR screening test • RPR+ve, FTA-ABS+ve Untreated syphilis Previously treated late syphilis • RPR-ve, FTA-ABS+ve 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

Syphilis Serology – Conventional Wisdom Screen with a Non-treponemal test (eg. an RPR, VDRL 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)

Changing Times in Syphilis Serology • Prevalence of syphilis is extremely low in many 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

Syphilis Serology – An Alternative Approach in Low Prevalence Settings Screen with a Treponemal 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.

What should we do with discordant treponemal/ non-treponemal results? For the first time we 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

Suggested Algorithm for Serological Screening for Syphilis Treponemal Test (No syphilis diagnosis. Recent infection Suggested Algorithm for Serological Screening for Syphilis Treponemal Test (No syphilis diagnosis. Recent infection cannot be ruled out ) + RPR - (Probably old treated syphilis. Treatment may be indicated if not previously treated) If false-positive screening treponemal test suspected, or if not previously treated, , retest with a different treponemal test. If second test is positive then treat unless there is a history of treatment -If second treponemal test is negative, a third treponemal test could be used to resolve the discrepancy between the two treponemal tests. + (Syphilis, old and new. Treatment usually indicated unless previously treated. Retreat if titer has increased > 4 fold)

Syphilis Serology The Conventional Wisdom Should Prevail in High Prevalence Settings • It is 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

Conclusions Treponemal screening alone has profound implications for both treatment of individuals and also 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.

Protocol for Tp + • Tp + and RPR + : untreated syphilis unless Protocol for Tp + • Tp + and RPR + : untreated syphilis unless R/O by Rx history • Tp + and >4 x titer RPR : new infection • Tp + but RPR – : Hx of previous Rx no further F/U No Hx of Rx: Obtain different 2 nd Tp If 2 nd Tp + then discuss with patient

2 nd Tp Test Obtain different 2 nd Tp (probably Tp WB): If 2 2 nd Tp Test Obtain different 2 nd Tp (probably Tp WB): If 2 nd Tp + then discuss with patient Unlikely infectious; treat for LLS If 2 nd Tp – then discuss with patient No further F/U Atkas et al; Int J STD AIDS 2007 MMWR Aug. 15, 2008

2006 CDC STD Treatment Guidelines Syphilis and PCN Allergy • Primary, Secondary, and Early 2006 CDC STD Treatment Guidelines Syphilis and PCN Allergy • Primary, Secondary, and Early Latent – Doxy 100 mg po bid or tetracycline 500 mg qid x 2 wks OR – Azithromycin 2 G po single dose OR – Ceftriaxone 1 g IM/IV daily x 8 -10 d • Latent Syphilis or Unknown Duration – Doxy 100 mg po bid or tetracycline 500 mg qid x 4 wks – Ceftriaxone? • Neurosyphilis – Ceftriaxone 2 g IM/IV daily for 10 -14 d as an alternative in neurosyphilis

Treatment of Partners, Suspect and Associates Screen: If < 90 Days : Rx if Treatment of Partners, Suspect and Associates Screen: If < 90 Days : Rx if + or – If > 90 Days: Rx if + No Rx if -

Policy for Billing 10. 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

HSV Diagnosis Provided by the State lab • Culture Not Provided by the State 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 Ig. G type specific tests include: – – Herpe. Select® ELISA HSV-2 or HSV-1 Herpe. Select® Immunoblot for HSV-2 and HSV-1 Biokit HSV-2 Rapid Test Sure. Vue HSV-2

When should type-specific serology be performed? • Recurrent genital symptoms or atypical symptoms with 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

Genital Herpes – Episodic Treatment • HIV-negative – Acyclovir 400 mg TID or 800 Genital Herpes – Episodic Treatment • HIV-negative – Acyclovir 400 mg TID or 800 mg BID x 5 d or 800 mg TID x 2 d – Famciclovir 125 mg BID x 5 d or 1000 mg BID x 1 d – Valacyclovir 500 mg BID x 3 d 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

Genital Herpes – Suppressive Therapy HIV • Acyclovir 400 mg po BID • Famciclovir Genital Herpes – Suppressive Therapy HIV • Acyclovir 400 mg po BID • Famciclovir 250 mg po BID • Valacyclovir 500 mg po qd • Valacyclovir 1 g po qd HIV+ • Acyclovir 400 -800 mg po BID-TID • Famciclovir 500 mg po BID • Valacyclovir 500 mg po BID

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