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Sarah E. Rutstein, MD, PhD University of North Carolina at Chapel Hill

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1 Sarah E. Rutstein, MD, PhD University of North Carolina at Chapel Hill
Public health implications of acute HIV infection diagnostic strategies in low- & middle-income countries Sarah E. Rutstein, MD, PhD University of North Carolina at Chapel Hill

2 What is acute HIV – a public health-centric definition
Why is it worth the effort? transmission cluster identification/intervention PrEP early treatment (not discussed here) How do we diagnose AHI? How do we miss AHI?

3 Acute HIV infection: Fiebig Stages
From: The Detection of Acute HIV Infection J Infect Dis. 2010;202(Supplement_2):S270-S277. doi: /655651 J Infect Dis | © 2010 by the Infectious Diseases Society of America

4 Defining acute HIV infection
HIV-RNA+

5 Defining acute HIV infection
HIV-RNA+ and/or p24 Ag

6 Defining acute HIV infection
HIV-RNA+ and/or p24 Ag Undetectable anti-HIV Ab

7 Defining acute HIV infection
HIV-RNA+ and/or p24 Ag Undetectable anti-HIV Ab Public health implications

8 What is acute HIV – a public health-centric definition
Why is it worth the effort? transmission cluster identification/intervention PrEP early treatment (not discussed here) How do we diagnose AHI? How do we miss AHI?

9  Efficient transmission
Volz et al., 2013 Proportion of New Infections Caused by Early Infections

10  Efficient transmission
Phylogenetic estimates and mathematical models highly variable  AHI accounts for 10-50% of all transmissions

11 AHI: Canary in a coal mine

12 AHI: Canary in a coal mine

13 PrEP: can we confirm HIV negative status without AHI screening?

14 What is acute HIV – a public health-centric definition
Why is it worth the effort? transmission cluster identification/intervention PrEP early treatment (not discussed here) How do we diagnose AHI? How do we miss AHI?

15 Diagnosing AHI

16 Diagnosing AHI

17 3rd vs 4th generation testing/NAT
WHEN <20 minutes Day(s) Field (anywhere) Access to lab/electricity/platform WHERE Fingerstick Venipuncture/whole blood WHAT Lay health-worker Skilled laboratory technician WHO 3rd generation (POC) 4th generation/NAT (not POC)

18 Alere Determine Ag/Ab Combo
Diagnostic pipeline Alere Determine Ag/Ab Combo

19 Alere Determine Ag/Ab Combo
Diagnostic pipeline Alere Determine Ag/Ab Combo POC Alere q HIV-1/2

20 Diagnostic pipeline Alere Determine Ag/Ab Combo POC Alere q HIV-1/2
GeneXpert HIV-1 Viral load

21 What is acute HIV – a public health-centric definition
Why is it worth the effort? transmission cluster identification/intervention PrEP early treatment (not discussed here) How do we diagnose AHI? How do we miss AHI?

22 How we miss acute infection…
Fever Fatigue Body pains Sore throat Genital ulcer disease Diarrhea AHI

23 AHI: more common than you’d think
Pilcher, et al., AIDS, 2004 Fiscus, et al., JID, 2007 Rutstein, et al., JAIDS, 2016 iKnow study (ongoing)

24 AHI: more common than you’d think
Seronegatives (n): 508 862 4255 9949

25 Focusing screening efforts
HIV Testing Centers vs Sexually Transmitted Infection Clinic (Lilongwe, Malawi, )

26 Beyond diagnostics: screening for AHI
Symptom-driven care seeking AHI risk score Score ≥2 Score <2 Offer HTC, consider alternative diagnoses HTC with rapid antibody Negative/discordant Positive Link to care/start ART AHI screening HIV RNA*/p24 Repeat HIV rapid antibody in 2-3 weeks No RNA/p24 available Adapted from: E. Sanders Many seek care during symptomatic phase Symptom- and risk behavior- derived risk scores concentrate scarce testing resources Screening <50% of patients can identify >80% of persons with AHI

27 …but perhaps the most critical component to AHI diagnosis is going to be standardized, global policy regarding, who, when, and how to test …worth the effort given significant public health implications regarding transmission, case-finding, and safety of PrEP initiation. Multiple barriers to diagnosis, including need for accurate POC screening tools… Brief period characterized by unfettered viral replication…

28

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