Fellow lecture at 03 FEB 2017 AVRC / HIV meeting.

1. A Count Too Low: Neutropenia in
Acute Retroviral Syndrome
Derek Larson
LT MC USN
Infectious Disease Fellow

2. DoD Disclaimer
The views expressed herein and those of
the author and do not purport to reflect
the position of the Department of
Defense, United States Navy, nor Naval
Medical Center San Diego.

3. Beginnings
• Mr. AR is 27 y/o active duty male
• Presenting syndrome:
– Abdominal pain
– Myalgias
– Arthralgias
– Headaches
– Sore throat
– Rectal pain
• ROS: Otherwise negative

4. History
• Medical
– Pseudofolloculitis barbae
– Syncopal episode 2 weeks prior
• Medications
– Alieve PRN
• Surgical
– Recent dental cleaning
• Allergies: NKDA

5. Social History
• Single
• Seaman (E3), A-school
• Previously worked at TWC
• Alcohol: Never
• Tobacco: Rare
• No recent travel / deployments
• Sexual: New female partner 1 month
ago, unprotected

6. Physical
• VS 102.3 71 116/59 18 97%RA
• Gen: AA gentleman in NAD
• HEENT: mild lymphadenopathy, normal
pharynx
• Heart: Normal rate, regular rhythm
• Pulm: CTA B/L
• Skin: No rashes
• Rectal: Normal

7. Labs
CBC: 4.0 > 14/75 < 75
Diff: 69% PMN, 17% Lymph
Chem: 136 / 3.6 / 98 / 24 / 1.4 < 122
UA: SG >1.060
Blood Cx x4: Negative

10. Course
• ER
– Cefotaxime 2 grams IV
– Admit to Gen Surg (re: Appy?)
• Gen Surg
– Serial abdominal exams
– Send: HIV rapid, Mono, Blood cx
– AM labs
– CBC: 2.1 > 13.2 / 38 < 67 43% PMN
– Medicine Consult
– Discharged day 2

11. Re-admitted
• 2 days later readmitted for fatigue,
increased pharyngitis, AKI, neutropenia
• Started: Unasyn > Vanc / Zosyn
• CT head neck without abscess
• Throat culture with E. aerogenes
• Discharged after 7 days with Moxifloxacin

12. Testing
• C-Reactive Prot 2.75
• Monospot: Negative
• Hepatitis A: Immune
• Hepatitis B: Immune
• Hepatitis C: Negative
• T. pallidum Ab: Negative
• Parvovirus: IgG+, IgM-
• CMV: IgG+, IgM-
• RVP: Negative
• Quant TB: Negative
• Triple Site GC/CT: Negative

13. HIV Testing
• Admit:
– HIV rapid: Negative
– HIV 1/2 Ab WB: Indeterminate
– HIV Viral Load: 17,000,000
• T cells
– CD4 absolute: 245
– CD8 absolute: 445
– CD4 ratio: 30%

14. HIV Treatment
• Started on Genvoya + Darunavir
• Viral loads
– JUL (Time 0): >10,000,000
– AUG: 96
– SEP: 60 (Discontinue Darunavir)
– OCT: 105

15. Topics
• Acute Retroviral Syndrome
• Impact of a drastically high viral load
• Therapy in ARS
• Overview of cytopenias in ARS

16. Acute Retroviral Syndrome
Ann Intern Med. 1996;124:654-663

17. Acute Retroviral Syndrome
Ann Intern Med. 1996;124:654-663

18. Acute Retroviral Syndrome
N Engl J Med. 2016 Jun 2;374(22):2120-30.

19. Acute Retroviral Syndrome
• Infectious timeline
3 days: Local infiltration / lymph
7-8 days: detectable viremia
10 days: most CD4+ cells involved
14-21: IgM ELISA
HIV-specific CD8+
Set point by week 8 – 24 (NEJM ~42 days)
Infect Dis Clin North Am. 2007 Mar;21(1):19-48

20. Acute Retroviral Syndrome
• What % get symptoms?
NEJM 2016: 96%
AIDS 2012: 41.4%
CID 2004: 40-90%
BMJ: 1994: 50%
AIDS 2012; 26:175-8

21. Acute Retroviral Syndrome
J Infect Dis. 1993;168:1490-1501

22. Acute Retroviral Syndrome
N Engl J Med. 2016 Jun 2;374(22):2120-30.

23. Acute Retroviral Syndrome
• Symptomatic (N=13)
• Asymptomatic (N= 27)
– Lower established viremia
– Higher level of antigenemia
– Slower decline in CD4+
• No differences in acute RNA levels
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jul 1;9(3):305-10

24. Acute Retroviral Syndrome
• Point of care field test (N = 8)
– 0% sensitivity for acute HIV
– 98% specificity for seroconverted
J Infect Dis, 2012;205(4):528-534

25. Acute Retroviral Syndrome
• Diagnosis of Primary HIV
p24 Ag: Sens 79% / Spec 99%
*Pooled data (77% to 91%)
3rd Gen EIA: 79% / 96%
HIV RNA: 100% / 97%
AIDS. 2002 May 24;16(8):1119-29.

26. Therapy in ARS
Infect Dis Clin North Am. 2007 Mar;21(1):19-48
NEJM 2013;368(3):218-230

27. Therapy in ARS
AIDSinfo.nih.gov, accessed Jan 14, 2016
JAMA. 2002 Jul 10;288(2):181-8
• Guidelines do not differentiate ARS and
chronic infection
• Noted genotypic resistance
transmission*:
– NRTI 20%
– NNRTI 13.2%
– PI 7.7%

29. Cytopenias
• Chronic = known
• Neutropenic work up
– Malignancies
– Viral disease (HIV 8% vs 16%)
• Acute Retroviral Syndrome
– Lymphopenia
– Thrombocytopenia – 45%
– Neutropenia - ?
J Intern Med. 2016 Jun;279(6):566-75
Arch Intern Med. 2006 Feb 27;166(4):405-10.

30. Neutropenia
• 1989 2 case reports
– 19 and 40 year old gentlemen
– ANCs 700 and 380
– No other pathogens
– Positive anti-granulocyte and anti-
thrombocyte antibodies
J Infect. 1989 Mar;18(2):167-70

31. Neutropenia
• 2005 case report (5th disease)
– 50 year old gentleman
– ANC 500
– No other pathogens
– Positive anti-granulocyte and anti-
thrombocyte antibodies
Eur J Intern Med. 2005 Apr;16(2):120-122

32. Neutropenias
• 2013 Case report
– 30 year old male
– ANC 400
– Bacillus cereus bacteremia?
CMAJ. 2013 Dec 10; 185(18): 1593–1596

33. Neutropenias
• Other case reports
– Presse Med 1998;27:161–2
– J Infect 1994; 28:315–8
– Infection. 1996 Jul-Aug;24(4):332-5
CMAJ. 2013 Dec 10; 185(18): 1593–1596

34. Lessons and Questions
• Although common in chronic infection,
neutropenia is uncommon in acute
• Symptoms fairly common, and portend
worse course
• Organizational efforts for ARS
recognition?

35. References
• Ann Intern Med. 1996;124:654-663
• J Infect Dis. 1993;168:1490-1501
• Curr Opin HIV AIDS. 2016 Sep 29
• N Engl J Med. 2016 Jun 2;374(22):2120-30
• Retrovirology 2013, 10:56
• J AIDS Hum Retrovirol. 1995 Jul 1;9(3):305-10
• AIDS 2012; 26:175-8
• Clin Infect Dis 2004;38(10):1447–53
• AIDS. 2002 May 24;16(8):1119-29.
• BMJ 1994;309(6968):1535–7
• Infect Dis Clin North Am. 2007 Mar;21(1):19-48
• J Infect Dis, 2012;205(4):528-534
• NEJM 2013;368(3):218-230
• Top Antivir Med. 2016 Dec-2017 Jan;23(5):156-60
• J Infect. 1989 Mar;18(2):167-70
• Arch Intern Med. 2006 Feb 27;166(4):405-10
• Eur J Intern Med. 2005 Apr;16(2):120-122