Acute HIV Infection: New Frontiers for HIV Prevention

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] • 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. 0 100 200 300 Blood viral load in acute HIV (n=171)Average fitted curve, with 95% confidence intervals log 10 HIV RNA 8 7 6 5 4 3 2 1 8-10 fold increase risk from peak to day 54 0 Days from Infection Peak: day 23 Pilcher, et al JID 2004

6. Semen viral load in acute HIV (n=30) log 10 HIV RNA 7 6 5 4 3 2 1 0 0 10 20 30 40 50 60 70 80 90 100 Days from Infection 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. Exposure to HIV at mucosal surface (sex) Day 0 Virus collected by dendritic cells, carried to lymph node Day 0-2 HIV replicates in CD4 cells, released into blood Day 4-11 Day 11 on Virus spreads to other organs Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39.

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. 40th IDSA, Chicago 2002.

22. Linear Gingival Erythema

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

24. 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 Schacker, T. et. al. Ann Intern Med 1996;125:257-264

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

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

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

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

40. CASE EXAMPLES

41. 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 African ImmigrantFrom: Natalie Neu, MD Columbia Presbyterian

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. 4th 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.15th-30th 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.10th Patient B develops fever (104) for 7-10D with fatigue, sore throat. Sees PMD given Z-pack & Vicodin • Sept.30th Patient C develops fever (101), sore throat, & rash. Sees PMD, given Z-pack

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

47. Transmission Network ABCD BA B C D + + + + +

48. Pooled Viral Load Testing in New York State

49. Pooling schema Individual specimens Pools of 10

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