1. Acute HIV Infection: New Frontiers for HIV Prevention Antonio E. Urbina, MD Medical Director HIV/AIDS Education and Training St. Vincent Catholic Medical Center

2. Definition of AHI Acute HIV infection or primary HIV infection is the first stage of HIV infection, last approximately 54 days.* Pilcher, NEJM 2005

3. Why Is Diagnosing AHI Is Vital

4. AHI Is Highly Infectiousness  High-titer viremia in plasma and genital fluids [1,2]  Absence of immune factors that may neutralize infectivity [2]  Between 100 and 3,000 times more infections than persons in chronic HIV infection [3] 1.Kahn JO, et al N Engl J Med 1998; 2. Quinn TC, et al N Engl J Med 2000 3. Jacquez JA, et al J Acquir Immune Defic Syndr 1994

5. 0 1 2 3 4 5 6 7 8 3002001000 log 10 HIV RNA Days from Infection Blood viral load in acute HIV (n=171) Average fitted curve, with 95% confidence intervals Peak: day 23 Pilcher, et al JID 2004 8-10 fold increase risk from peak to day 54

6. 1009080706050403020100 7 6 5 4 3 2 1 0 log 10 HIV RNA Days from Infection Semen viral load in acute HIV (n=30) Pilcher, et al JID 2004

7. AHI Disproportionately Contributes to Onward HIV Transmissions  29-50% of new HIV transmissions are attributable to acute HIV infection [1,2,3, 4] Xiridou et al., 2004; Yearly et al, 2001; Pao et al, 2005, Bluma et al, 2007.

8. Treating HIV Is Hugely Expensive  Lifetime Cost of HIV Care in the US in the Current Treatment Era $619,000 B R Schackman, et al. Journal of Medical Care, 2006

9. Pathogenesis of AHI

10. Question 1 Which organ contains the most T-cells? A. The lymph nodes B. The gastrointestinal tract C. The blood D. The spleen

11. Model of Pathogenesis For Acute HIV-1 Infection

12. Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39. Exposure to HIV at mucosal surface (sex) Virus collected by dendritic cells, carried to lymph node HIV replicates in CD4 cells, released into blood Virus spreads to other organs Day 0 Day 0-2 Day 4-11 Day 11 on

13. Question 2 All patients that go through AHI will be symptomatic. Is this statement True: A. Yes B. No

14. Question 3 Which of following symptoms is typically not present in persons experiencing AHI: A. Generalized lymphadenopathy B. Rash C. Fever D. Cough E. Meningismus

15. SYMPTOMS OF AHI

16. Acute HIV Infection (www.hivguidelines.org)

21. Oral Ulcers in Acute HIV Infection From: Walker, B. 40 th IDSA, Chicago 2002.

22. Linear Gingival Erythema

23. Genital Ulcer in Acute HIV Infection From: Walker, B. 40 th IDSA, Chicago 2002.

24. Schacker, T. et. al. Ann Intern Med 1996;125:257-264 Days from sexual exposure to onset of symptoms in 12 patients who could identify the exact date and time of the sexual exposure that led to acquisition of human immunodeficiency virus

25. Detection of HIV by Diagnostic Tests 0 1 2 3 4 5 6 7 8 9 10 Symptoms p24 Antigen HIV RNA HIV EIA* Western blot Weeks Since Infection *3 rd generation, IgM-sensitive EIA After Fiebig et al, AIDS 2003; 17(13):1871-9 *2 nd generation EIA *viral lysate EIA

26. + S EIA and –LS +S EIA and –LS EIA dates infection to within 4-6 months Detuned Assay

27. DIAGNOSING AHI?  How effective are we?

28. Acute HIV Infection (AHI) Nearly 60 million individuals diagnosed with HIV, fewer than 1,000 cases have been diagnosed in AHI [1] –1/60,000 detection rate [1] Pilcher, et al AIDS 2004

29. Why so lax in diagnosing AHI?  1. Treatment and diagnosis of HIV infection has been relegated to specialists Lack of education of how to diagnose AHI Discomfort related to difficult issues surrounding HIV  2. Clinicians inability to spend the additional time Flanigan T, et al Annals of Int Med 2001

30. AHI : Look and Ye Shall Find 1% of patients with negative tests for EBV had AHI [1] 1% of patients with “any viral syndrome” in a Boston urgent care center had AHI [2] In a Malawi STD clinic, 2.8% of all male clients with acute STD had AHI [3] [1] Rosenberg, et al N Engl J Med 1999 [2] Pincus, et al Clin Infect Dis 2003 [3] Pilcher, et al AIDS 2004

31. Schacker, T. et. al. Ann Intern Med 1996;125:257-264 Clinical Presentation of HIV Seroconversion*

32. How to diagnose AHI (in New York State)

33. ICD-9 Code for AHI (exposure to HIV) VO1.79

35. Question 4 Which of the following lab tests is typically normal in persons in AHI A. CBC B. LFTs C. Metabolic Panel D. Cerebrospinal fluid

36. Tests to Order  HIV antibody  HIV viral load test  Met panel  CBC  LFTs

37. Counseling Patients Avoid breast feeding or unprotected sex, drug paraphernalia sharing while test is pending If AHI reactive: –Always practice safe sex and drug using behavior; emphasize that patient is highly infectious –Ask patient about sexual and needle sharing contacts. Work with NYCDOH to do rapid contact tracing.

38. Behavior Change After Diagnosis Multi-Site Acute HIV Infection Study –27 participants (most of them MSM) completed assessments of their sexual behavior before and after diagnosis of AHI Results –Significant drop in the # of sexual partners after diagnosis (p=0.05) –After diagnosis, more than 95% of sex acts were with people who were also HIV-positive (sero-sorting) –No significant change in the number of sex acts, but a significant increase in sex using condoms. (p=.001) Steward WT, et al, NIMH Multi-Site Acute HIV Infection Study 2007

39. “Acute Case” “Efficient disseminator” Clustering: efficient dissemination by core groups and identification of networks Identification via PHI Identification of network

40. CASE EXAMPLES

41. African Immigrant From: Natalie Neu, MD Columbia Presbyterian 2/05: African woman gives birth in Bronx (NSVD) Mother and baby both test HIV negative 5/05: mother visits ER in Bronx and is diagnosed with viral syndrome. Is told its okay for her to breast feed. 6/05: infant admitted for gastroenteritis; plts 85 8/05: admitted for plt 7 and treated for Idiopathic Thrombocytopenia Purpura (ITP) –Fever, periorbital edema,  LFTs, pancytopenia 9/05: ID consulted. Baby diagnosed with PHI

42. HIV Evaluation 2/05: – Newborn HIV screen negative 9/05 –Rapid HIV 1/2 – positive; Western blot indeterminate –HIV Plasma RNA > 750,000 –T cells 2095 (56%)

43. Four Men 20 yo male (Patient A) July 29 headache, fever Aug. 2 – Local Emergency Department (ED)  Underwent Lumbar Puncture (LP)  Placed on Doxycycline. Possible dx Rocky Mountain Spotted Fever (RMSF)? Aug. 4 th presented to another Local ED and admitted with  headache, fever, nausea, vomiting  Labs: WBC 4.4; Plt 115,000;  RMSF Ab negative, HIV ELISA Ab neg. Discharge Dx: Post LP H/A; Possible viral ( aseptic) meningitis

44. Four Men cont. Patient A’s symptoms resolve Aug.15 th -30 th Patient A has sex with Partner (Patient B): 21 y/o male They have unprotected sex 3-4x Patient C, 22 y/o male joins for 3-way sexual encounter with Patients A & B Aug.30-Sept.9th Patient B and C have sex 1-2x/week

45. Four Men Cont. Sept.10 th Patient B develops fever (104) for 7-10D with fatigue, sore throat. Sees PMD given Z-pack & Vicodin Sept.30 th Patient C develops fever (101), sore throat, & rash. Sees PMD, given Z-pack

46. Four Men, Cont. Oct. 15 th -20 th Patients B & C have three way sexual encounter with patient D Oct.28 th – 30th Patient D develops sore throat, oral ulcers, thrush & fever Oct.31 st Partner D visits MD & requests STI W/U ; no HIV testing done Nov.3 rd Patient D Dx with lymphoma and requests HIV testing Nov. 15 th HIV ELISA + & WB Indeterminate suggesting early infection

47. Transmission Network A B C D B A B C D + + + +

48. Pooled Viral Load Testing in New York State

49. Individual specimens Pools of 10 Pooling schema

50. A B C D E Pooling schema A B C D E Individual specimens N=100 Pools of 10 F G H I J K

51. Master pool Pooling schema Individual specimens N=100 Pools of 10 A B C D E F G H I J K

52. A Individual testing on 10 specimens Pools of 10 screened Master pools screened Resolution Testing A B C D E

53. Question 5 Which of the following statements about pooled viral load testing is not correct? A. It improves the specificity and decreases the cost of screening large numbers of persons in AHI B. It can identify asymptomatic patients experiencing AHI C. It is currently being done in all DOH clinics in NY State D. Can be performed by “robotic” testing

54. 1 Master Pool 1-Stage Pooling 16 Individual Specimens Pooling Procedure (NYC STD Clinics) Slide courtesy of P. Patel

55. HIV Screening, Select NYC STD Clinics, May 5 – October 1, 2008 Confidential Rapid HIV Ab tests N = 11,847 HIV Ab+ Tests N = 108 Submitted for HIV Viral Testing N = 11,739 HIV Ab- Tests N = 11,739 Screening start dates: Jamaica 05/05/2008; Ft. Greene 06/02/2008; Chelsea 06/23/2008

56. AHI Screening, Select NYC STD Clinics, May 5 – October 1, 2008 11,739 specimens sent for pooled PCR PCR positivity: –Overall (12/11,739) = 0.10% Jamaica (1/4,417) = 0.02% –1 AHI case per 4,417 HIV Ab– – 23 HIV Ab+ PLUS 1 HIV RNA+ → Increases HIV Dx by 4% Ft. Greene (3/3,745) = 0.08% –1 AHI case per 1,248 HIV Ab– – 32 HIV Ab+ PLUS 3 HIV RNA+ → Increases HIV Dx by 9% Chelsea (8/3,577) = 0.22% –1 AHI case per 447 HIV Ab– –53 HIV Ab+ PLUS 8 HIV RNA+ → Increases HIV Dx by 13% May 5 – October 1, 2008

57. AHI Screening, Select NYC STD Clinics, Cases by Race/Ethnicity Total N = 12 May 5 – October 1, 2008 n = 6 n = 3 n = 1 75% of new AHI cases in minority populations

58. AHI Cases by Risk Factors Reported at Time of Interview May 5 – October 1, 2008 Case Number 12345 Occupation PsychologistExotic Dancer/Escort FinanceReal EstateFinance MSM Yes Drug use AlcoholCrack cocaineAlcoholNoAlcohol Incarcerated NoUnkNo Internet Hook-ups YesUnkYes Sex for Drugs/$$ NoUnkNo UAI Yes HIV+ Partner Yes

59. Case 678910 Occupation Flight AttendantDisabilityUnemployedHandyman/ Odd jobs Mail room clerk MSM YesBisexual Yes Drug use No Alcohol, cigarette, Marijuana No Incarcerated NoYes 2004 No Internet Hook-ups YesNo Sex for Drugs/$$ NoYes 2006 No UAI YesNoYesNoYes HIV+ Partner YesN/AYes – indicated in EMR Yes AHI Cases by Risk Factors Reported at Time of Interview May 5 – October 1, 2008

60. Algorithm for AHI Screening FEVER Cough or nasal congestion yes AHI less likely; ask about high risk sexual or needle sharing <8 weeks yes Consider Screening for AHI no Treat underlying infection no Presence of: rash pharyngitis LAN arthralgias/myalgias mucocutaneous ulcers H/A/meningitis no Screen for AHI yes