1. HIV Point of Care tests in Babies Study (BABY) Operational evaluation of HIV Point of Care tests for very early infant HIV diagnostics in infants born from HIV infected mothers in Mbeya, Tanzania
Arne Kroidl

2. Baby Study Study design: Non-invasive in-vitro diagnostic study
Study population: N=600 HIV+ mothers & exposed neonates from Mbeya, Tanzania
HIV PoC Test: - Cepheid Xpert HIV-1 Qual PoC (neonates)
- Cepheid Xpert HIV-1 Qual PoC from DBS (neonates)
- Cepheid Xpert HIV-1 VL (mothers at delivery)
Confirmatory HIV diagnostics:
DBS HIV-DNA (Roche COBAS TaqMan)
plasma HIV-RNA viral load (Roche COBAS TaqMan)
End of Study
Week 6
Delivery/Birth
Week 1
Week 2
Week 3
PoC
Neonatal Xpert HIV-1 Qual
Martenal Xpert HIV-1 VL

3. Baby Study Primary objective Secondary objectives
Operational specificity, sensitivity and predictive values of the Xpert Qual HIV-1 to identify vertical HIV newborn transmission
Secondary objectives
Assessments of neonatal HIV transmission rates and at different time points (intra-uterine, peri-/postnatal) and define the optimal time point to detect the highest number of peripartal transmissions at the earliest possible occasion.
Evaluation of the Xpert Qual HIV-1 from dry blood samples (DBS)
Evaluation of the Xpert HIV-1 Viral load test in mothers at delivery
Practical feasibility of implementing early newborn diagnostics in de-centralized African Health Care settings

4. Maternal Characteristics
N=614 neonates born from 606 HIV-infected women included
(8 twin pairs) included
Variable
N=614
Age, median (range)
29 (18-44)
Mode of delivery
Vaginal, at hospital
498 (81.1%)
Vaginal, at home
25 (4.1%)
Caesarean section
89 (14.5%)
Not on ART at delivery
51 (8.3%) 
CD4 count categories
<200 cells/µL
97 (15.8%)
200 to 350 cells/µL
156 (25.4%)
>350 cells/µL
353 (57.5%)
Plasma HIV-RNA* >1000 copies/mL
133 (21.7%)
Plasma HIV-RNA* >1000 copies/mL on ART
89 (15.9%)
* Measure by Roche TaqMan

5. Maternal HIV-RNA at delivery (N=574)
Comparison of SoC plasma VL (Roche TaqMan) versus
PoC plasma VL (Cepheid HIV-1 Xpert Quant)
N=11
Xpert >1000 c/mL
TaqMan <1000 c/mL
Log HIV-RNA (Xpert)
N=6
Xpert <1000 c/mL
TaqMan >1000 c/mL
Log HIV-RNA (TaqMan)
Good agreement between VL results
HIV-1 Xpert VL overall higher than TaqMan VL

6. Maternal HIV-RNA at delivery
Comparison of SoC plasma VL (Roche TaqMan) versus
PoC plasma VL (Xpert HIV-1 VL)
Bland Altman Analysis
→ only quantifiable HIV-RNA results included
lower limit: log
mean difference: 0.3 log
higher limit: 1.2 log

7. Vertical HIV transmission – infected neonates
N=15 neonatal HIV transmissions detected by Xpert Qual HIV-1 PoC correctly confirmed by DBS HIV-DNA and/or plasma VL (Roche TaqMan)
Neonatal HIV Status until Week 6 post-partum
N=614
HIV-infected neonates
15 (2.4%)
At birth
10 (66.7%)
Week 1 post-partum
2 (13.3%)
Week 2 post-partum
1 (6.7%)
Week 3 post-partum
Week 6 post-partum
The majority on HIV infected infant had evidence for intra-uterine HIV transmission

8. Vertical HIV transmission – infected neonates
Maternal risk-factors associated with vertical HIV transmission (n=infected infants/N=mothers with factor)
Maternal risk factor
n/N (%)
RR (95% CI)
p-value
Not on ART at delivery
4/51 (7.8%)
4.0 ( )
0.014
VL >1000 copies/mL
14/133 (10.5%)
50.4 ( )
<0.001
On ART at delivery but VL >1000 copies/mL
10/89 (11.2%)
53.7 ( )
CD4 count <200 cells/µL
9/97 (9.3%)
7.8 ( )
Non-adjusted Poisson regression, RR=risk factor

9. Cepheid Xpert Qual HIV-1 PoC Baby Diagnostic
All whole blood Xpert Qual PoC results
correctly identified neonatal HIV infection (no false negative test result)
Confirmed by positive DBS qualitative HIV-DNA and/or plasma VL at the time of test positivity
correctly identified HIV negativity (no false positive test result)
Confirmed by negative DBS qualitative HIV-DNA at Week 6
but….

10. Case 1
The Xpert Qual HIV-1 PoC demonstrated greater sensitivity to detect early HIV transmission (week 1) as compared to the DBS HIV-DNA and plasma HIV-RNA.
Birth
Week 1
Week 2
Week 3
Week 6
Xpert HIV-1 Qual POC
(whole blood)
negative
positive
DBS Soc HIV-DNA
(Roche TaqMan)
Plasma HIV-RNA SoC -
< 34
Xpert HIV-1 Qual POC (DBS)
Infant ARV’s
NVP
Plasma HIV-RNA Soc VL (mother) (Roche TaqMan)
41.900

11. Case 2
Negative HIV tests at week 6 → possibly due to infant NVP prophylaxis
Routine HEID procedures at week 6 would have missed HIV infection
Birth
Week 1
Week 2
Week 3
Week 6
Week 10
Xpert HIV-1 Qual POC
(whole blood)
positive
negative
DBS Soc HIV-DNA
(Roche TaqMan)
Plasma HIV-RNA SoC
53.100 -
<34
292
Xpert HIV-1 Qual POC (DBS)
Infant ARV’s
NVP
ZDV+3TC+NVP
Plasma HIV-RNA Soc VL (mother) (Roche TaqMan)
15.100

12. Case 3
Negative HIV tests at week 6 → possibly due to infant NVP prophylaxis
Routine HEID procedures at week 6 would have missed HIV infection
Birth
Week 1
Week 2
Week 3
Week 6
Week 10
Xpert HIV-1 Qual POC
(whole blood)
positive
negative
DBS Soc HIV-DNA
(Roche TaqMan)
Plasma HIV-RNA SoC
1.570 - 75
Xpert HIV-1 Qual POC (DBS)
Infant ARV’s
NVP
ZDV+3TC+LPV/r
Plasma HIV-RNA Soc VL (mother) (Roche TaqMan)

13. Cepheid Xpert Qual HIV-1 PoC - Operational performance -
Birth testing
HIV-PoC testing at birth
N=614
Time between birth and testing, median (range)
16 hours (0.5-58)
Test performed
<12 hours after birth
233 (38.0%)
12 to 24 hours after birth
222 (36.2%)
24 to 48 hours after birth
129 (21.0%)
>48 hours after birth
9 (1.5%)
Missing information
21 (3.4%)

14. Cepheid Xpert Qual HIV-1 PoC - Operational performance -
Test performance at the health facilities
PoC test performed
N=2736
Valid test result obtained
2673 (97.7%)
Time between sample collection and result communication to the mother of valid test results, median (range)
110 minutes (94 minutes to tab 7 days)
No valid test result obtained
63 (2.3%)
PoC test problem reported by nurses
183 (6.7%)
Early terminated analysis because of power cut
106 (57.9%)
Error/invalid result message
61 (33.3%)
Problem with computer or analyser handling
4 (2.2%)
Clotted blood
2 (1.1%)
No reason indicated
10 (5.5%)
PoC testing had to be repeated
132 (4.8%)
PoC testing performed at other site (sample transferred)
210 (7.7%)

15. Cepheid Xpert Qual HIV-1 PoC - Operational performance -
Opinions by nurses (N=24)

16. Conclusion
100% sensitivity & specificity of the whole blood Xpert Qual HIV-1 PoC to detect neonatal HIV infection
Requirement for neonatal test & immediate antiretroviral treat approaches
In some cases:
Whole blood Xpert with greater sensitivity as compared to DBS testing
False negative EID-HIV results for all tests at week 6
Good operational feasibility and acceptance among nurses/midwives
Greatest challenge: power-cuts
The greatest risk for vertical transmission is high maternal viral load at delivery
Need for maternal PoC HIV-RNA monitoring for potential treatment adjustment or extended neonatal prophylactic regimens
Good agreement seen between maternal Xpert HIV-1 VL and TaqMan

17. Acknowledgment Mbeya Medical Research Center & Mbeya Referral Hospital
Clinic
Issa Sabi (PI)
Hellen Mahiga (cordinator)
Debora Kikaro (nurse)
Sarah Mlelwa (nurse)
John France (HoD Obs & Gyn MRH)
Data Management
Peter Agrea
Willyhelmina Olomi
Lab
Abidai Kisinda
LMU Munich
Arne Kroidl
Otto Geisenberger (monitoring)
Sabine Kastner (monitoring)
Fidelina Zekoll (data managment)
Conny Luer (local lab management)
Michael Hoelscher
Cepheid South Africa
Dipti Lallubhai
Gwynn Stevens
Funder:
All nurses and midwives at the Mbeya study sites !
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