NEW CHALLENGES FOR ACCURATE HIV-1 DIAGNOSISbreach-hiv.be/media/docs/BREACHSpring2018/BREACH... · Nom de la présentation 23 90.4% HIV-1 9.6% IND Evolution of the 9.6% IND results

ALL BELGIAN AIDS REFERENCE LABORATORIESKAROLIEN STOFFELS (ARL VUB STP) & FIEN VANROYE (ARL ITM)

NEW CHALLENGES FOR ACCURATE

HIV-1 DIAGNOSIS

30 NOVEMBER 2018, BRUGGE0

ALL BELGIAN AIDS REFERENCE LABORATORIESKAROLIEN STOFFELS (ARL VUB STP) & FIEN VANROYE (ARL ITM)

NEW CHALLENGES FOR ACCURATE

HIV-1 DIAGNOSIS

30 NOVEMBER 2018, BRUGGE2

3Nom de la présentation

1st serology screen test for HIV reactif (Ag+Ab)

2nd serology screen test for HIV (Ag+Ab)

confirmation test (Ab)

- Immunoblot (INNO-LIA HIV I/II - FujiRebio)- Immunochromatography (Geenius HIV 1/2 - BioRad)- Western Blot (HIV Blot 2.2 - MP Biomedicals)

additional tests (Ag p24, VL) if confirmation is negative or indeterminate

Very sensitive but less specific

Very specific but less sensitive

DIAGNOSIS HIV IN BELGIUM


INNO-LIA HIV I/II Score Geenius HIV 1/2 HIV Blot 2.2

NEG

gp120

gp41

p31

p24

p17

gp105

gp36

gp1

60

gp1

20

p6

6p

55

p5

1

gp4

1

p3

9

p3

1

p2

4

p1

7

Seru

mco

ntr

ol

HIV

-2

IND

HIV-1

HIV-1 + 2

HIV-1HIV-2

HIV-2 HIV-1

HIV-1 HIV-2

controlsC

DIAGNOSIS IN RESOURCE-CONSTRAINT SETTINGS:RAPID TESTS

5


BM Branson, Acquir Immune Defic Syndr 2010,vol 54th

TEST WINDOW PERIOD

RAPIDS


DIAGNOSIS HIV IN CASE OF ART?






CASE: BRAZILIAN PATIENT 2006 : HIV diagnosis in Brasil

2007: start treatment

2009: follow-up in ARC STP

Date SCREENING INNO-LIA VL (cp/ml)

28/09/2009 POS IND <40

06/12/2011 POS IND <20

06/06/2012 POS IND <20

04/2012 : STOP TREATMENT

28/09/2012 POS HIV-1 54600

10/2012 : RESTART TREATMENT Atripla

14/03/2013 23

18/07/2013 <20

7.2% (386/5331) of requested confirmations are not performed

because the patients are already known as HIV infected in the corresponding ARL (2017)

11

Taking any treatment?

No...


INFLUENCE OF ART ON HIV DIAGNOSISIN BELGIUM?


GROUP 1: CHRONIC GROUP 2: ACUTE

Treatment for >10 years Start treatment during acute infection

Standard confirmation testsused in Belgium

Rapid tests used in resource-constrained settings

EFFICIENT TREATMENT

ARL STUDY ON HIV DIAGNOSTIC TESTS IN BELGIUM

RAPID TESTS

First Response

Assay Manufacturer CE WHO

Abon HIV1/2/O Tri-Line Rapid Test Device Abon, China No Yes

Determine HIV 1/2 Alere Health, Japan Yes Yes

First Response HIV 1.2.O Card TestPremier MedicalCoorporation, India

Yes Yes

INSTI HIV TestBiolytical Laboratories, Canada

Yes Yes

SD Bioline HIV 1/2 Alere Health, Japan Yes Yes

HIV 1/2 STAT PAK Chembio, USA Yes Yes

Rapid test for Ab to HIV (colloidal gold) Wantai, Shanghai No Yes

Abon

SD Bioline

STAT PAK

Determine

Wantai

First Response

14


Inclusion criteria:

- Patients with HIV-1 VL <50 cp/ml for at least 10 years with a maximum interval between 2 consecutive VL determinations of 18 monthsno blips allowed

- With documented results at least uptill end 2016

388 patients, undetectable VL for 14 years in average [10y ; 21y]

GROUP 1: chronic, treatment >10 years


1.5% (6/388) was not confirmed to be HIV-1 positive

98.5% HIV-1(382)

1.3% IND (5)0.2% NEG (1)

CONFIRMATION REFERENCE TESTING ON MOST RECENT SAMPLE: GEENIUS OR INNO-LIA OR WB


98.5% HIV-1(382)

1.3% IND (5)0.2% NEG (1)

Reference tests

96.3%

(368)

3.7% (14)

GROUP 1: chronic, treatment >10 years (388 patients)

All (7) Rapid Tests Reactive

≥1/7 Rapid Test Non Reactive

17

17% (1)

83% (5)

Rapid testsRapid tests


18




Inclusion criteria:- All patients diagnosed HIV-1 in 2010 or later

and not lost to follow-up after diagnosis 2010-2018

- With documented acute HIV-1 infection HIV confirmation test negative or indeterminate AND Ag p24 positive or RNA VL positive acute only

- AND started efficient treatment within 3 months no blips once undetectable viral load has been obtained treatment started between 0 and 88 days after diagnosis

83 patients included in study

GROUP 2: ART during acute infection


90.4%HIV-1 (79)

9.6%IND(8)

routine confirmation test: (INNO-LIA OR Geenius OR MP Blot 2.2)

Most recentsample

time1st sample

HIV-1 acute infectionFollow-up

samples

9.6% (8/83) were not confirmed as HIV-1 positive

GROUP 2: ART during acute infection (83 patients)


90.4%HIV-1(79)

9.6%IND(8)

routine confirmation test: (INNO-LIA OR Geenius OR MP Blot 2.2)

Start treatment after diagnosis

Q1 0 – 6 days

Q2 7 – 13 days

Q3 14 – 39 days

Q4 40 – 88 days

19

16

2119

1

5

02

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Q1 Q2 Q3 Q4


HIV-1 IND

timeFollow-up

samplesMost recent

sample

1st sample HIV-1 acute infection

GROUP 2: ART during acute infection (83 patients)


90.4%HIV-1

9.6%IND

Evolution of the 9.6% IND results

Follow-up samples Most recent sample

NEG IND

HIV-1

IND

NEG / IND IND

INDNEG ?

time

3 patients

4 patients

1 patient

A1CRF36CRF01_AE

Time betweenfirst and recent sample

BBBCRF02_AG

1.7 years3.7 years3.1 years2.0 years

B 0.4 years


54 days

12 days12 days7 days47 days

Subtype

2.4 years1.8 years0.4 years

8 days7 days0 days

1st sample HIV-1 acute infection

All (7) Rapid Tests Reactive

≥ 1/7 Rapid Test Non Reactive

90.4%HIV-1

(75)

9.6%IND (8)

Reference tests


24

74,7% (56)

25,3% (19)

62,5% (5)

37,5% (3)

Rapid testsRapid tests


25

Conclusion studyReference testing Rapid testsA

cute

Ch

ron

ic

98.5% HIV-1(382)

1.3% IND (5)0.2% NEG (1)

26


DIAGNOSIS HIV IN CASE OF PREP?

CASE: ITM PREP PATIENT Date Screening Antigen Confirmation

(Geenius)Inno- Lia HIV-1

Viral load (cp/ml)

HIV-1 DNA

CD4 Therapy

06/2017 NEG/NEG NEG / / / / / /

07/2017 START PREP TRUVADA

07/2017 NEG/POS NEG NEG / <60 / / TDF/FTC

09/2017 POS/POS NEG NEG / / / / TDF/FTC

12/2017 START TRITHERAPY STRIBILD

12/2017 POS/POS NEG IND (gp41) IND (gp41) <20 NEG 844 EVG/c/TAF/FTC

03/2018 POS/POS NEG IND (gp41) / <20 / 1029 EVG/c/TAF/FTC

Additional tests performed in Ghent: all tests are negative

28

Conclusion: Do we need other markers for diagnosis?

Screening tests

Confirmation tests (blots)

Rapid tests

DNA detection

RNA viral load

Ag/Ab basedNAT

29


Thank you!

Any questions?

31

Documents

NEW CHALLENGES FOR ACCURATE HIV-1 DIAGNOSISbreach-hiv.be/media/docs/BREACHSpring2018/BREACH... · Nom de la présentation 23 90.4% HIV-1 9.6% IND Evolution of the 9.6% IND results