A Count Too Low: Neutropenia in Acute Retroviral Syndrome

Derek LarsonLT MC USN

Infectious Disease Fellow

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.

Beginnings• Mr. AR is 27 y/o active duty male

• Presenting syndrome:– Abdominal pain– Myalgias– Arthralgias– Headaches– Sore throat– Rectal pain

• ROS: Otherwise negative

History• Medical– Pseudofolloculitis barbae– Syncopal episode 2 weeks prior

• Medications– Alieve PRN

• Surgical– Recent dental cleaning

• Allergies: NKDA

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

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

LabsCBC: 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

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

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

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

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%

HIV Treatment• Started on Genvoya + Darunavir

• Viral loads– JUL (Time 0): >10,000,000– AUG: 96– SEP: 60 (Discontinue Darunavir)– OCT: 105

Topics• Acute Retroviral Syndrome

• Impact of a drastically high viral load

• Therapy in ARS

• Overview of cytopenias in ARS

Acute Retroviral Syndrome

Ann Intern Med. 1996;124:654-663

Acute Retroviral Syndrome

Ann Intern Med. 1996;124:654-663

Acute Retroviral Syndrome

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

Acute Retroviral Syndrome• Infectious timeline

3 days: Local infiltration / lymph7-8 days: detectable viremia10 days: most CD4+ cells involved14-21: 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

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

Acute Retroviral Syndrome

J Infect Dis. 1993;168:1490-1501

Acute Retroviral Syndrome

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

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

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

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.

Therapy in ARS

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

Therapy in ARS

AIDSinfo.nih.gov, accessed Jan 14, 2016JAMA. 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%

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):566-75Arch Intern Med. 2006 Feb 27;166(4):405-10.

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

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

Neutropenias• 2013 Case report– 30 year old male– ANC 400– Bacillus cereus bacteremia?

CMAJ. 2013 Dec 10; 185(18): 1593–1596

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

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?

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