1. Performance of two HBV rapid diagnostic tests to identify pregnant women at risk of HBV mother-to-child transmission (MTCT) in Cambodia: the pilot ANRS study
Dieynaba N’Diaye
Poster MOPDC 0105
Abstract number A
O. Ségéral, D.S. N’Diaye, S. Prak, W. Khamduang, J. Nouhin, M. Ek, K. Chim, S. Hout, AM. Roque-Afonso, P. Piola, N. Ngo-Giang-Huong, F. Rouet, for the ANRS Study Group 

2. during the third quarter of Immediate immunoprohylaxis
RATIONAL
Background
International guidelines suggest/recommend the administration of anti-HBV drugs (as Tenofovir [TDF]) during the third trimester of pregnancy if HBV DNA viral load (VL) levels > 5.3 Log10 IU/mL (associated to immunoprophylaxis) to reduce HBV mother to child transmission (MTCT)1
How to apply these guidelines in Cambodia?
Prevalence: 5-10% in general population but screening rate very low2,3
Poor laboratory facilities in health care centers where antenatal care (ANC) takes place
Very poor access to HBV DNA VL quantification, notably in decentralized areas
Objective
To evaluate the performance of a new diagnosis algorithm using HBsAg and HBeAg rapid diagnostic tests (RDTs) (SD Bioline) to identify pregnant women at high risk of HBV MTCT.
Methodology
250 pregnant women during ANC at Calmette Hospital (Phnom Penh), with at least 125 HBsAg +, were tested with the RDT-based algorithm and compared to gold standards:
1) Performance of the SD Bioline HBsAg RDT to detect HBV infection vs. HBsAg ELISA (Murex v3.0 Diasorin) among all pregnant women
2) Performance of the SD Bioline HBeAg RDT as a surrogate marker of high VL vs. HBV DNA quantification (PUMA HBV kit, Omunis, Clapiers) among women found positive for HBsAg
during the third quarter of
Immediate immunoprohylaxis
1 - Sarin et al; Asian-Pacific clinical practice guidelines on the management of hepatitis B.Hepatol Int.2016 ; 2 - Yamada H et al; Hepatol Res ; 3 - Reekie J et alJ Gastroenterol Hepatol. 2013
ANRS study, IAS 2017

3. RESULTS: RDTs performance
Study population
250 pregnant women; median age 29 years; 51.2% (128) were HBsAg+
Among 128 HBsAg+
34 (26.5%) with HBV DNA > 5.3 Log10 IU/mL and 28 (21.2%) > 7.3 Log10 IU/mL
29 (23%) tested positive with HBeAg RDT
ANRS study, IAS 2017

4. RESULTS: Distribution of HBV DNA VL and HBeAg RDT
Figure 1: Distribution of HBV VL for the 128 women with positive HBsAg
Figure 2 HBV DNA VL according to HBeAg test results
Among HBV-infected women
63% have very low HBV VL
26% have high VL
HBV DNA VL median of positive HBeAg RDT was 8.4 vs for negative HBeAg RDT (significant difference, Fisher exact test p-value = 3.1e-9)
during the third quarter of
Immediate immunoprohylaxis
ANRS study, IAS 2017

5. RESULTS: Discordant cases
BCP/PC mutations for the 8 women with negative HBeAg RDT and HBV DNA > 5,3 Log10 IU/mL ID
HBeAg results
Log10
IU/mL
(VL) GT
BCP/PC mutations
Mutation profile
ELISA
RDT
1762
1764
1858
1862
1888
1896
CAL128 + -
7.78 C T A
GCAC G
BCP T1762A1764 mutant
CAL220
6.90
CAL223
6.47 R
BCP T1762A1764/PC A1896 mutant
CAL002
6.45
CAL143
7.80 Y
CAL169
7.60
CAL126
6.49 B
Wild Type
CAL005
6.13
7/8 87,5% of the woman carring the BCP/PC mutation negative HBeAg RDT but HBV DNA > 5,3 Log UI/mL
negative HBeAg RDT with HBV DNA VL > 5.3 Log IU/mL
ANRS study, IAS 2017

6. DISCUSSION HBsAg RDT to detect HBV infection during ANC
Excellent sensitivity and specificity
Point of care, low cost, adapted to routine screening during ANC in decentralized areas
HBeAg RDT to predict HBV DNA levels among HBsAg+ women
Excellent specificity / lower sensitivity (related to BCP/PC HBV mutants)
Sensitivity increases for higher HBV DNA level (>7.3 Log10 IU/mL)
Need to be confirmed with larger and more representative sampling (ANRS TA PROHM study)
HBV DNA levels and risk of transmission
Very low risk of transmission for 63% of HBV-infected women, and high risk for 26%
TDF showed effectiveness and safety to reduce MTCT for high risk women in China4 and is largely available in Cambodia
Algorithm could be useful and cost-effective to detect pregnant women at risk of HBV MTCT and predict TDF indication in a country where HBV VL is not routiney available
Impact of BCP/PC HBV mutants needs to be confirmed in a larger sample size
Pan CQ et al;N Engl J Med. 2016
ANRS study, IAS 2017