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. 4 th 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.15 th -30 th 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.10 th Partner A develops fever (104) x 7-10D fatigue, sore throat sees PMD given Z-pack and Vicodin Sept.30 th Partner B fever (101),sore throat,+/- rash Sees PMD given Z-pack

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

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

10. Calculated transmission probabilities based on semen HIV viral load at peak (d23), set point (d120) Rank log spVL Prob/actOdds Prob*/120d 75 th %ile 5.58.0381:26.126 50 th %ile 4.79.0091:107.032 25 th %ile 3.88.00181:556.006 Assumes 8 coital acts per month Pilcher CD, et al., XIVth Int AIDS Conf, 2002

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

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

13. Two-Fold Benefit of Detecting AHI 1.Individual Perspective –Improve prognosis with acute treatment???? –Entry into care and treatment 2.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

14. 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

15. The acute retroviral syndrome 49-89% symptomatic (Schacker TW, et al., AIM 1996 125:257-64) Symptoms SchackerKinloch-de Loes Fever93%87% Fatigue9326 Pharyngitis7048 Weight loss7013 Myalgias6042 Headache5539

16. 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

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

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

22. 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

23. Acute HIV and the North Carolina STAT Project

24. 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

25. 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

26. False Positive Rates Problem with Individual Screening p24 Antigen0.2% HIV RNA PCR1-7%* *False positives <10,000 copies/ml HIV RNA

27. 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

28. 90 individual specimens 9 intermediate pools (10 specimens) 1 master pool (90 specimens) Pooling and resolution testing

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

30. Nov. 02- March 23 2006 Yr 1Yr 2Yr 3Yr4 # True +692220216 # False RNA + 52210 # False EIA neg. 21100 #Comm.8011232125

31. 2/3 of AHI cases Dx from STD clinics 2002-2003

32. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% HIV Test STD Clin Drug Trt Prenatal Jail/Prison Low-risk “Other” Overall Antibody-negative HIV Infections as a Proportion of All Detected Cases 6% 4%1%

33. 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

34. 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

35. 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

36. 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

37. 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

38. HCV Risk Factors ParenteralSexualPerinatal IVDUMultiple partnersHigh viral load Nasal cocaineTraumaticHIV (+) TransfusionsHIV (+) 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.

39. 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.

40. 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 Poynard et al. Lancet. 1997;349:825-832. NIH Consensus Development Conference Statement. June 10-12, 2002; Bethesda, Md.

41. 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

42. 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!

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