The how and why of Acute HIV Infection 1. How do we best diagnosis patients with acute HIV?

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1 Acute HIV infection Eric Rosenberg, MD Associate Professor of Pathology Director, Clinical Microbiology Laboratory Massachusetts General Hospital Harvard Medical School

2 The how and why of Acute HIV Infection 1. How do we best diagnosis patients with acute HIV? Clinical presentation Differential diagnosis Laboratory markers 2. Why should we diagnosis patients with acute HIV? Transmission Treatment Treatment interuption

3 Diagnosis

4 How often do we see Acute HIV? 0.3% consecutive, unselected ED visits (Clark, JID 1994) 1% urgent care clinic patients with any symptom of a viral illness at BMC (Pincus, CID 2003) 1% of MGH patients tested for EBV mononucleosis with a negative heterophile (Rosenberg, NEJM 1999)

5 How do patients with acute HIV present?

6 Commonly reported signs and symptoms fever >80-90 % fatigue >70-90 % rash % myalgia/arthralgia % pharyngitis % Lymphadenopathy > 50% nightsweats 50 % n/v/d %

7 Less commonly reported signs and symptoms Leukopenia/thrombocytopenia % weight loss 25 % aseptic meningitis 24 % anorexia 21 % increased LFT s 20 % oral ulcers % genital ulcers 5-15 % cough/uri diagnosis very unlikely

8 Acute HIV Differential diagnosis EBV (1% of negative mono spots = ARS) CMV Streptococcal infection/pharyngitis HSV Influenza Acute Hepatitis A, B and C Toxoplasmosis (acute) Rubella/Measles Endocarditis

9 Which of the following patient s has acute HIV?

10 Patient 1: A 35 year old man with fever, rash, fatigue and nausea 35 year old man (IVDU) presents to the emergency room with: Fever to Rash Fatigue Nausea, anorexia, diarrhea WBC 7, HCT 42, PLT 290, Ast 478, Alt 509, Tb 2.3 Does this patient have acute HIV?

11 What is the diagnosis? 1. Acute HIV infection 2. Bacterial endocarditis 3. Acute Epstein-Barr virus infection 4. Acute Cytomegalovirus infection 5. Acute Hepatitis C infection

12 Patient 1 Rapid strept test negative HIV ELISA negative HIV RNA < 50 copies /ml plasma EBV heterophile negative CMV IgM negative, IgG positive HCV Ab negative HCV RNA > 700,000 copies/ml Dx= Acute Hepatitis C virus infection

13 Patient 2: A 20 year old man with fever, sore throat, lymphadenopathy and weight loss 20 year old MSM presents to MGH medical walk-in clinic complaining of: Fever X 2 weeks (103.2 on exam) Sore throat, Lymphadenopathy Fatigue, myalgia, arthralgia Nausea, vomiting, diarrhea and abdomen cramps. 8 lb weight loss WBC 1.5, 12% atypical lymphocytes, HCT 40, Plt 127, ALT 240, AST 280 Does this patient have acute HIV?

14 What is the diagnosis? 1. Acute HIV infection 2. Bacterial endocarditis 3. Acute Epstein-Barr virus infection 4. Acute Cytomegalovirus infection

15 Patient 2 HIV ELISA negative HIV RNA < 50 copies /ml plasma EBV heterophile negative CMV IgM 5 units, IgG Negative CMV DNA Positive HCV Ab negative HCV RNA undetectable Dx= Acute CMV infection

16 Patient 3: 47 year old male with fever, headache and photophobia Present to MGH ED with an 8 day history of : Fever to Headache Photophobia Myalgias and arthralgias Nausea and vomiting 3 rd visit to health care system

17 47 year old male Exam: Fever Oral ulcer Cervical lymphadenopathy Rash (started on torso spread to limbs and scalp) Data: WBC 7.6 (ALC 0.75) CSF 11 WBC s (70% lymphocytes)

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20 Data: WBC 7.6 (ALC 0.75) 47 year old male EBV monospot negative CMV IgM negative, CMV IgG + CSF 11 WBC s (70% lymphocytes) HIV 4 th generation screening test (Ag/Ab) Positive HIV-1/2 differentiation assay Negative HIV RNA: 47,000,000 copies/ml

21 Diagnosis Acute HIV Infection

22 Diagnosis

23 Laboratory Markers and Terminology Branson, JAIDS 2010

24 Making the diagnosis of Acute HIV Must have a very high level of suspicion Risk factors Physical exam critical HIV ELISA 4 th generation (Ab/Ag) closes window ~7d HIV-1/HIV-2 Differentiation assay HIV RNA

25 Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations Branson et al, CDC/APHL

26 Why is it important to make the diagnosis of Acute HIV infection?

27 Transmission Making the diagnosis of acute HIV infection help may stop unknowing transmission of HIV

28 Transmission of HIV is greatest during acute and early HIV infection 12 times more likely to transmit Wawer et al, JID 2005:191 Time after seroconversion

29 Treatment Should individuals with Acute HIV-1 infection be treated with antiretroviral therapy?

30 Advantages Preservation of HIV-specific cellular immune responses Opportunity for structured treatment interruption Lowering of HIV-1 set point Limitation of viral evolution and diversity Decreased transmission Mitigation of acute retroviral symptoms Disadvantages Toxicities and unknown long-term risks Short- and long-term clinical benefits are not well-defined Resistance acquisition Limitation of future antiretroviral therapy options Quality of life impact Cost Kassutto et al, Clinical Infectious Diseases 2006

31 SPARTAC trial Short Pulse Antiretroviral Therapy at Seroconversion 48 weeks course of therapy delayed disease progression although not much longer than the course of treatment NEJM, January 17, 2013

32 Primo-SHM Trial: No Treatment versus 24 or 60 weeks of Antiretroviral Treatment during Primary HIV infection Strongest evidence to date that early therapy may delay need for therapy in chronic infection Grijsen et al, PLOS Medicine, March 2012

33 Conclusions The early events in acute HIV infection may represent a unique window of opportunity for treatment It is not known whether treatment during acute infection is the right thing to do Making the diagnosis of Acute HIV infection is the correct thing to do Treatment followed by discontinuation of therapy may have a role in management of acute infection but optimal approach not known.