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Acute HIV and the North Carolina STAT Project

Acute HIV and the North Carolina STAT Project. Index. 20 yo white male July 29 Headache, fever Aug. 2 – Local ED Underwent LP Placed on Doxycycline … …possible Lyme Aug. 4 th presented to another Local ED and admitted Headache, fever, nausea, vomiting

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Acute HIV and the North Carolina STAT Project

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  1. Acute HIV and the North Carolina STAT Project

  2. Index • 20 yo white male • July 29 Headache, fever • Aug. 2 – Local ED Underwent LP Placed on Doxycycline … …possible Lyme • Aug. 4th presented to another Local ED and admitted Headache, fever, nausea, vomiting labs: WBC 4.4; Plt 115; RMSF Ab, TRUST, HIV ELISA Ab- neg. Discharge Dx: Post- LP H/A Possible viral ( aseptic) meningitis

  3. Transmission • Index symptoms resolve • Aug.15th-30th Index has sex with Partner A: 21 W male They have unprotected sex 3-4x Partner B : 22 W male joins for 3-way • Aug.30-Sept.9th Partner A&B have sex 1-2x/week

  4. AHI Partners A&B • Sept.10th Partner A develops fever (104) x 7-10D fatigue, sore throat sees PMD given Z-pack and Vicodin • Sept.30th Partner B fever (101),sore throat,+/- rash Sees PMD given Z-pack

  5. Transmission • Oct. 15th-20th Partners A&B have three way Partner C • Oct.28th – 30th Partner C Sore Throat, oral ulcers, thrush, fever • Oct.31st Partner C visits LMD requests STI W/U ; antib./ no HIV test • Nov.3rd Partner C Dx Lymphoma and requests HIV test • Nov. 15th HIV ELISA + WB Indet.

  6. Transmission Index with AHI Transmission to A B Transmission to C C Dx AHI; And B come in for rapid testing on World AIDS Day

  7. Acute HIV • The window period between: - Appearance of HIV in blood - Host Antibody response • Seroconversion defined as “confirmed” by + WB • Time period may narrow with newer generation ELISAs

  8. Couthino et al., Bulletin of Mathematical Biology 2001

  9. Calculated transmission probabilities based on semen HIV viral load at peak (d23), set point (d120) Ranklog spVLProb/actOddsProb*/120d 75th %ile5.58 .038 1:26 .126 50th %ile 4.79 .009 1:107 .032 25th %ile 3.88 .0018 1:556 .006 • Assumes 8 coital acts per month • Pilcher CD, et al., XIVth Int AIDS Conf, 2002

  10. Transmission of HIV/coital act Raki Wawer et al, JID 2005

  11. Diagnostic Testing Timeline Symptoms p24 Antigen HIV RNA HIV ELISA 0 1 2 3 4 5 6 7 8 9 10 Weeks Since Infection Recombinant peptide ELISA Viral lysate ELISA Fiebig et al, AIDS 2003;17(13):1871-9

  12. Two-Fold Benefit of Detecting AHI • Individual Perspective • Improve prognosis with acute treatment???? • Entry into care and treatment • Public Health • Recognized previously missed infections • Avoid transmission to partners with risk reduction and ART • 10-100 fold increased transmission risk x 5 months • May be responsible for ½ all transmission of HIV - ID Transmission networks and geographic focus transmission networks partners at high risk targeted interventions identify high risk transmiitter

  13. Pitfalls in AHI • Diagnosis rarely pursued/rare event • 30-40% of patients may be asymptomatic • Signs and symptoms non-specific • few clues • Laboratory testing must be directed

  14. The acute retroviral syndrome • 49-89% symptomatic (Schacker TW, et al., AIM 1996 125:257-64) • Symptoms SchackerKinloch-de Loes Fever 93% 87% Fatigue 93 26 Pharyngitis 70 48 Weight loss 70 13 Myalgias 60 42 Headache 55 39

  15. Primary (Acute) HIV:PE abnormalities • Erythematous non-specific rash • Lymphadenopathy • Mucocutaneous ulcerations (oral/vaginal/esophageal) • Pharyngitis • Neurologic abnormalities (including encephalitis) • Oral manifestations • Serious OI’s rare

  16. Laboratory abnormalities • Lymphocytopenia • Other -cytopenias • Atypical lymphocytosis rare early • Elevated transaminases • Lymphocytic pleocytosis and elevated protein in CSF

  17. Dx AHI • How • Considerations for which test - sensitivity -specificity - positive and negative predictive value - through put - cost

  18. Ways to reduce transmission • Identify AHI • Behavior change….. Abstain during hyper-infectious period (8 wks) • HAART- to lower viral load ASAP • Screen for STI • Urgently trace partner network

  19. Acute HIV and the North Carolina STAT Project

  20. North Carolina’s Perfect Storm • Named reporting • PCRS • Central Lab • Moderate prevalence • Integrated surveillance and field service • Integrated STD and HIV Branch • Close relationship UNC ID and UNC SPH

  21. Our Approach to detection of AHI • Screening of all HIV Ab negative or WB indeterminate Blood from public clinics for HIV RNA • Review of all community cases - Ab neg., HIV RNA + - Ab.+ with Hx neg. HIV Ab within 3 mo - Ab + but with recent acute symptoms

  22. False Positive Rates Problem with Individual Screening • p24 Antigen 0.2% • HIV RNA PCR 1-7%* *False positives <10,000 copies/ml HIV RNA

  23. How to make AHI Screening Possible: Specimen pooling • Advantages Cost (Quinn, et al. AIDS 2000;14:2751-2757 ) Specificity Improved positive predictive value • Disadvantages Requires large testing volume Reduced sensitivity Logistics • STAT has provided proof of concept: Screening for AHI IS feasible in a routine testing population using ultrasensitive RT-PCR

  24. A B C D E F G H I A B C D E F G H I 1 2 3 4 5 6 7 8 9 10 A B C D E F G H I A B C D E F G H I Pooling and resolution testing 90 individual specimens 9 intermediate pools (10 specimens) 1 master pool (90 specimens)

  25. Clinical Reporting (2) EIA/WB + - NAAT Long Term HIV Positive + - F/U Testing (Ab+NAAT) + - HIV Negative Acute HIV

  26. Nov. 02- March 23 2006

  27. 2/3 of AHI cases Dx from STD clinics 2002-2003

  28. Antibody-negative HIV Infections as a Proportion of All Detected Cases 100% 90% 1% 6% 6% 6% 4% 80% 70% 60% 50% 40% 30% 20% 10% 0% “Other” Overall Prenatal Low-risk HIV Test Drug Trt STD Clin Jail/Prison

  29. The Future • Expand AHI screening in ERs, Urgent Care, and inpatient settings • Remove barriers for HIV testing in the above settings • Remove need for written informed consent ( not required by law) • Remove requirement for pre-test counseling • Limit post-test requirement to positives only • Develop predictive models for AHI screening and testing

  30. Who is joining the party • Colorado • Baltimore STD clinics • FLA demonstration project • LA STD clinics • New York City • New York State – Rochester • San Francisco STD clinics • Seattle MSM and SEP

  31. NC STD clinics and AHI • Entry point for high risk individuals • Overlap of incubation periods of classic STIs and HIV • Already drawing blood for syphilis • Opt out approach for HIV testing • Integration of HIV and STD programs

  32. Rapid Testing “Plus”: Specimens • Fingerstick or oral fluid testing makes effective HIV antibody testing possible in non-traditional settings • most HIV testing is in traditional settings • Venous blood is routinely obtained for diagnostic tests at most HIV testing sites (STD clinics, prenatal clinics, SEP activities, etc) • Patients prefer non-venipuncture rapid tests…but “preference” does not mean mutually exclusive choices nor does it justify missing AHI

  33. Conclusions • Continued exclusive use of HIV antibody tests will miss 4-10% of truly HIV+ individuals, at the precise moment of their maximum transmission potential • With emergent results notification and PCRS, acute HIV screening is direct HIV prevention • STAT has immediate impact on vertical HIV transmission • STAT is cost effective • Acute screening can be used to “back up” rapid tests

  34. HCV Risk Factors Parenteral Sexual Perinatal IVDUMultiple partners High viral load Nasal cocaine Traumatic HIV (+) Transfusions HIV (+) Transplant Occupational exposure Tattoos/Body piercing Manicures Household items Toothbrush, razor HIV (+), positive for human immunodeficiency virus; IVDU, intravenous drug use. NIH Consensus Development Conference Statement. June 10-12, 2002; Bethesda, Md.

  35. SEXUAL TRANSMISSION: RECOMMENDATIONS • Inform HCV carriers of risks • Test partner for HCV • No modification of long-standing monogamous relationships • Safer sex for promiscuous behavior • Some concern that genital ulcerative diseases ( LGV,HSV) may facilitate HCV tranmsission.

  36. Factors Associated With Disease Progression • Alcohol consumption • 30 g/day in men • 20 g/day in women • Disease acquisition at >40 years • Male • HIV coinfection • Hepatitis B virus coinfection NIH Consensus Development Conference Statement. June 10-12, 2002; Bethesda, Md. Poynard et al. Lancet. 1997;349:825-832.

  37. The co-infection dilemma • High co-infection rate of HCV in HIV infected • Few dually infected receive HCV therapy Why? • Administration of therapy • Historically poor response rates • Coverage of therapy cost • Dual and triple diagnosis • Liver Bx • Lack of experienced care providers

  38. What to do • Raise awareness of the HCV epidemic • Cross train HIV providers in HCV management • Provide free screening for at risk populations - currently only 1 health department offers free HCV screening • Surveillance – both chronic and acute HCV - develop acute HCV screening ( variation of pooling mech.) - increase free screening • Expand coverage for HCV therapy • Vaccinate at risk populations for HAV and HBV • GET PROVIDERS to TREAT!

  39. What to do is not solely dependent on therapy • Vaccinate for HAV and HBV • Council on reducing ETOH • Risk reduction for transmission

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