3 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
4 Awareness of Serostatus Among People with HIV and Estimates of Transmission new infections~45% of~25%unawareof infection~75%awarePLWHANew infections each year4
5 Identification of HIV Status to Reduce Transmission Goal of new CDC recommendations to increase number who know HIV+ statusPeople do not perceive riskClinicians do not offer testStigma of identified risk and of testingKnowing HIV+ status can reduce transmission by: Behavior change- HAART reducing viral loadMMWR 55:1-7, 2006Inungu J. AIDS atient Care STDs 16:293, 2002
6 Knowledge of HIV Infection and Behaviour Results: The analysis integrating all 11 findings indicated that the prevalence of UAV with any partner was an average of 53% (95% confidence interval [CI]: 45%–60%) lower in HIV+ persons aware of their status relative to HIV+ persons unaware of their status. There was a 68% reduction (95% CI: 59%–76%) after adjusting the data of the primary studies to focus on UAV with partners who were not already HIV+. The reductions were larger in between-group comparisons than in within-subject comparisons. Findings for men and women were highly similar.Reduction in unprotected anal or vaginal intercourse with HIVNegative 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. 20056
7 Source of HIV tests and Positive Tests 38-44% of adults yrs. have been tested16-22 million aged yrs. tested/yr in U.S.HIV Tests HIV+ TestsPrivate MD/HMO % %Hospital/ED/Outpt % %Public clinics % %HIV C&T % %Drug treatment % %Correctional facility % %STD clinics % %National Health Interview Survey,2002; Suppl; to HIV/AIDS surveillance,
8 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 13-64Providers 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 infectionAll 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.
9 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."
10 Changes to NC Administrative Code Nov. 1, 2007 Providers and Laboratories to report HIV/AIDS from 7 days to 24 hrsHIV 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.
11 Changes to NC Administrative Code Nov. 1, 2007 Opt-out HIV screening in medical settings and for prenatal and STD visitsPretest counseling not requiredPost-test counseling required only for positivesHIV tests at first prenatal visit and 3rd trimesterMandatory HIV test at L&D for all women for whom HIV status is unknown and in infant if test not obtained from mother
12 General Consent FormI 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_____________
13 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
15 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.
16 Rules ChangesNOTE: 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.Pre-test counseling is no longer required for HIV testing.
17 Window Periods for HIV Tests Stekler J. et al CID 2007
18 HIV viremia during early infection Peak viremia: gEq/mLHIV RNA (plasma)Ramp-up viremiaDT = 21.5 hrsHIV AntibodyHIV p24 Agp24 Ag EIA -Viral set-point: gEq/mLHIV MP-NAT -1st genHIV ID-NAT -2nd gen4th gen3rd gen“blip” viremia111622102030405060708090100
19 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
20 Non-specific Mononucleosis-like Signs and Symptoms FeverRashOral ulcerWeight lossLoss of appetiteHeadacheFatigueAdenopathySore throat/ pharyngitisMuscle and/or joint painDiarrheaGI upset/nausea/vomiting
21 Common Signs & Symptoms Study of 160 patients with primary HIV infection in 3 countries% of patientsVanhems P et al. AIDS 2000; 14:
22 Role of Rapid Antibody Testing Makes testing feasible in non-traditional settingsHighly effective for outreach situations (needle exchange, bathhouse testing, “street-corner” outreach)Increases receipt of positive HIV test resultsWhere HIV results notification (PCRS) not in placeMight increase requests for HIV testingIs not preferred in many established testing settingsCost 2-3x ELISA Ab testsMay defer resource allocation to HIV negativesMay miss AHI
23 PCR Testing of Pooled Sera to Identify Acute HIV Infection (seronegative, PCR positive) Source: ISSTDR, 200723
24 Typical Course of Primary HIV 1 mil100,00010,0001,000100HIV RNAHIV RNAHIV-1 AntibodiesAbP24 +Typical Sequence of Events in Primary HIV EventInfection 0Entry of virus into bloodstream 3-7Detectable HIV-1 RNA 7-14Detectable p24 antigenOnset of symptoms (Lindbach)Peak viremia 21 days, initial doubling time 10 hours (Little, J Exp Med 1999)Antibody seroconversion 24 days (Lindbach)Even following the introduction of MP-NAT, a preseroconversion donation with a viral load of ≤ 150 copies of RNA/ml went undetected and resulted in an HIV transmission. (Delwart et al, Vox Sanguis, 2004; 86:171-1.)+_ExposureSymptoms10314212835DaysSource: Hecht. Primary HIV.24
25 Efforts to date to detect and follow up with newly acquired HIV/HCV infections have attempted to highlight the signs and symptoms of a seroconversion illness.However, despite infection of nearly 60 million individuals worldwide with HIV, fewer than 1,000 cases have been diagnosed in the first month of infection, primarily because of a lack of a specific and recognizable acute retroviral syndrome.Since acute retroviral syndromes mimic many common febrile illnesses, the true diagnosis (acute HIV) is rarely considered at an initial patient encounter.25
26 SPREAD THE WORD - NOT HIV ACUTEHIVSYNDROMEIf 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 ILLNESSESCommon Symptoms of Acute HIV:High FeverRashFatigueSwollen GlandsSore ThroatNausea/VomitingNight SweatsSymptoms usually appear about2 weeks after exposureWhat Puts You At Risk?Unprotected SexSharing NeedlesThe Acute HIV ProgramIf 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 DepartmentsScreening 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.SPREAD THE WORD - NOT HIV
31 HIV Testing Goals Universal testing of individuals 13-64 yr Opt-out testing in STD/ Prenatal/Prison settingsAllow uncoupling of pre- and post-test counseling from HIV testing itselfThink and test for AHI ( RNA) with “mono-like” illness in sexually active adult……. Fast Track
33 Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990–2004Note: Resistant isolates have ciprofloxacin MICs ≥ 1 µg/ml. Isolates with intermediate resistance have ciprofloxacin MICs of µg/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990.
34 Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001–2004
35 GonorrheaDo not use quinolones (cipro, oflox, levo)
36 Previous Recommendations 2006 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefpodoxime 400 mg PO x 1orCeftriaxone 125mg IMAlternatives: Gentimicin 240 mg IM ( not for oral pharyngeal)- do test of cureQuinolones: Do test of cureCiprofloxacin 500mg POOfloxacin 400mg POLevofloxacin 250mg POAzithromycin 2.0 g PO ( expensive, nausea and vomiting)Add co-treatment for Ct if not treating with AzithromycinPlus, Azithromycin 1g PO or Doxycycline 100mg po BID x 7d
37 2008 NC STD Treatment Guidelines Uncomplicated Gonorrhea Cefixime 400 mg PO x 1orCeftriaxone 125mg IMAlternatives: Gentimicin 240 mg IM ( not for oral pharyngeal)- do test of cureQuinolones: Do test of cureCiprofloxacin 500mg POOfloxacin 400mg POLevofloxacin 250mg POAzithromycin 2.0 g PO ( expensive, nausea and vomiting)Add co-treatment for Ct if not treating with AzithromycinPlus, Azithromycin 1g PO or Doxycycline 100mg po BID x 7d
51 Reactivity of Non-treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment
52 Serologic Tests for Syphilis Test Sensitivity by stage of untreated syphilis SpecificityPrimary Secondary Latent LateVDRL % % % 37-94% %RPR % 100% % 73% %TRUST % % % %MHA-TP % % % 94% %FTA-ABS % 100% % %Sensitivity increases with duration of lesion in primary syphilis (serology becomes positive when chancre has been present for avg. of 14 days).Expect titer of nontreponemal test to be >1:16 in secondary syphilis.Prozone phenomenon, a rough or weakly reactive appearance seen when there is excess antigen in the serum, occurs in 1-2% of secondary syphilis.Variation of plus or minus one dilution is expected; an increase of one dilution then may be due to the variability in the test, but increase of two dilutions cannot be attributed to this and suggests treatment failure or reinfection.MHA-TP a little more specific than FTA-ABS.
60 DiaSorin Liaison Treponemal Chemiluminescence Assay – Principle of Test
61 Reactivity of Treponemal Serological Tests by Stage of Syphilis and Influence of Successful Treatment
62 Use of Treponemal and Non-treponemal Tests to Monitor Impact of Specific Interventions for Syphilis Among STD PatientsTreponemal15% Seropositive10Non-treponemal51245Time (Years)
63 Interpretation of Serological Tests for Syphilis RPR+ve, FTA-ABS-veFalse positive RPR screening testRPR+ve, FTA-ABS+veUntreated syphilisPreviously treated late syphilisRPR-ve, FTA-ABS+veVery early untreated syphilisPreviously treated early syphilisRPR-ve, FTA-ABS-veNot syphilisIncubating syphilisVery late syphilisSyphilis with concomitant HIV infectionNote: These possible interpretations do not necessarily have equal weight
64 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)
65 Changing Times in Syphilis Serology Prevalence of syphilis is extremely low in many industrialized countriesLabor costs have increasedIntroduction of treponemal tests which can be fully automated
66 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.
69 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
70 Suggested Algorithm for Serological Screening for Syphilis Treponemal TestRPR-+(Syphilis, old and new. Treatment usually indicated unless previously treated. Retreat if titer has increased > 4 fold)(No syphilis diagnosis. Recent infection cannot be ruled out )(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 treatmentIf second treponemal test is negative, a third treponemal test could be used to resolve the discrepancy between the two treponemal tests.
71 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 highLabor costs largely remain low in comparison to the cost of test kitsThe capital and maintenance costs of automated systems may be prohibitive
72 ConclusionsTreponemal 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.
73 Protocol for Tp +Tp + and RPR + : untreated syphilis unless R/O by Rx historyTp + and >4x titer RPR : new infectionTp + but RPR – :Hx of previous Rx no further F/UNo Hx of Rx:Obtain different 2nd TpIf 2nd Tp + then discuss with patient
74 2nd Tp Test Obtain different 2nd Tp (probably Tp WB): If 2nd Tp + then discuss with patientUnlikely infectious; treat for LLSIf 2nd Tp – then discuss with patientNo further F/UAtkas et al;Int J STD AIDS 2007MMWR Aug. 15, 2008
75 2006 CDC STD Treatment Guidelines Syphilis and PCN Allergy Primary, Secondary, and Early LatentDoxy 100mg po bid or tetracycline 500mg qid x 2 wks ORAzithromycin 2 G po single dose ORCeftriaxone 1 g IM/IV daily x 8-10dLate Latent Syphilis or Unknown DurationDoxy 100mg po bid or tetracycline 500mg qid x 4 wksCeftriaxone?NeurosyphilisCeftriaxone 2 g IM/IV daily for 10-14d as an alternative in neurosyphilis
76 Treatment of Partners, Suspect and Associates Screen:If < 90 Days : Rx if + or –If > 90 Days: Rx if +No Rx if -
77 Policy for Billing"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 establishedc) 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
78 HSV Diagnosis Provided by the State lab Culture Not Provided by the State LabPCR (Not FDA approved for genital site)Western blotFDA Approved IgG type specific tests include:HerpeSelect® ELISA HSV-2 or HSV-1HerpeSelect® Immunoblot for HSV-2 and HSV-1Biokit HSV-2 Rapid TestSureVue HSV-2Detection of HSV-2 Antibody Using Type Specific SerologyWhen no lesion is available to culture or the lesion has started healing, consider type specific serology. There are several accurate type specific serology tests available.Western Blot is the gold standard test for HSV-2, developed by Dr. Rhoda Ashley Morrow at the University of Washington. It is not commercially available, however the lab does accept shipments from offices. Call for information. Cost to the patient is approx. $ Results are available in 4-6 days.There are FDA Approved IgG type specific serology tests available. There are also many non-type specific tests on the market so it’s important to know which test your lab runs.The sensitivity and specificity for the HSV-2 tests are listed below:*Sensitivity SpecificityWestern Blot HSVHerpeSelect ELISAHerpeSelect Immunoblot HSVbiokitHSV-2 onlySurevue HSV-2* Test results should be correlated to clinical history and epidemiologic data, as the likelihood of a false-positive result increases with decreasing underlying prevalence of HSV-2.GSK does not warrant the accuracy of any diagnostic tests. Please consult the manufacturers for further information about these products.HerpeSelect is a registered trademark of Focus Diagnostics, Inc. GSK has no financial interest in Focus Diagnostics.biokitHSV-2 Rapid Test is owned by biokit. GSK has no financial interest in biokit.Captia is a trademark of Trinity Biotech. GSK has no financial interest in Trinity.References:1. HerpeSelect Product Information. Focus Diagnostics, Oct. 15, 2004.2. biokit Package Insert. July 16, 2004.
79 When should type-specific serology be performed? Recurrent genital symptoms or atypical symptoms with negative HSV culturesClinical diagnosis of HSV without lab confirmationPartner with genital herpes? patients with multiple sexual partners, HIV+ patients and MSM
80 Genital Herpes – Episodic Treatment HIV-negativeAcyclovir 400 mg TID or 800 mg BID x 5d or 800mg TID x 2dFamciclovir 125 mg BID x 5d or 1000mg BID x 1dValacyclovir 500 mg BID x 3d or 1 g qd x 5 dHIV-positiveAcyclovir 400 mg TID x 5-10 dFamciclovir 500 mg bid x 5-10 dValacyclovir 1 G bid x 5-10 d
81 Genital Herpes – Suppressive Therapy HIV-Acyclovir 400mg po BIDFamciclovir 250mg po BIDValacyclovir 500mg po qdValacyclovir 1g po qdHIV+Acyclovir mg po BID-TIDFamciclovir 500mg po BIDValacyclovir 500mg po BIDHIV+ persons are likely to be more contagious for HSV. The extent to which suppressive antiviral therapy will decrease HSV transmission from this population is unknown. Some specialists suggest routine suppression of HSV-2+ HIV+ individuals, even if they are asymptomatic
82 HSV and PregnancyTo date, no increased risk of birth defects in women treated with acyclovir during 1st trimesterMore limited data for valacyclovir and famciclovirMany specialists recommend HSV suppression during third trimester in order to prevent C-section