Introduction to Rapid HIV

Diagnostic Algorithm (rHIVda)

2023
Objectives
• Provide a background of the rHIVda (rapid HIV diagnostic
algorithm)

• Discuss validation method of the rHIVda study and its

alternative algorithms

• rHIVda Expansion
2
NRL-SLH/SACCL
• 1980’s Naval American Research Unit (NAMRU)
• 1996 developed as a Japan Int’l Cooperation Agency (JICA-DOH) Project
• 2000 designated as NRL for HIV, Hepatitis and other STIs
• 2001 administrative management of SLH, Philippine Gov’t Funding
• 2014 Accredited to Laboratory Accreditation Standard ISO/PNS 15189:2013
• 2016 Approval of New Building Construction : HIV Training Center
• 2022 Undergoing discussion of Incorporation into the Bill for Creation of CDC
• Philippines
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NRL-SLH/SACCL

• 2001 Started Confirmatory testing for HIV

• 2001 to 2008:
< 50 confirmed cases per month
test run 2x a month

• average # confirmed positives per month:

2015 : 655
2016 : 708
2017 : 800++
2018: 1,200
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Previous National HIV Referral System
• All HIV testing laboratories
must refer the initially 1,350+ HIV
reactive blood sample to the laboratories
NRL
• Average # of HIV referrals
per month: 1,500
• Referring lab shoulder cost
of specimen transport
NRL SLH/SACCL
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 NRL-SLH/SACCL Turnaround time: 10 days
• Western blot
has been used
since the late
’80s HIV Screening Tests

Western blot Nucleic Acid Test

NRL SLH/SACCL (gold standard) (NAT)
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 PRE-TEST education and/or
counselling:
National HIV Testing Ensure informed consent

Algorithm (NRL SACCL) First HIV rapid/IA test

(screening test)

Positive test result* Negative test result:

• Used since 2001(17yrs) Counsel for negative
• No misdiagnosis Refer to NRL-SACCL result

• Current NATIONAL HIV 2 Parallel Tests :

2 IA or IA + Rapid
TESTING ALGORITHM
(Diagnostic - uses 3 test BOTH POSITIVE DISCORDANT test Negative test result
test result: results: Counsel for negative
platform) result
HIV confirmatory test:
WESTERNBLOT

NEGATIVE test result: INDETERMINATE POSITIVE test result:

Counsel for negative Repeat test after 6w- Counsel for positive 8
result 3mos-3mos result
Concerns
• Long turnaround time of results
• Clients do not return, laboratory shopping
• Laboratories pool their referrals
• High cost of Western blot and its significant
number of Indeterminate results
• Consequently lead to low rates of treatment
initiation

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rHIVda?
• An algorithm using a combination of 3 rapid test
formats done in sequence on a sample that was
reactive in the initial HIV test.
• Decentralization of HIV confirmatory testing from the
NRL to Certified rHIVda Confirmatory Laboratories -
CrCLs

10
History of rHIVda
• 2013 Protocol development (DOH, SACCL, WHO); REC approval;
sample bank preparation, collection of samples
• 2014 Sept start validation testing of 18 DOH-FDA approved kits
• 2015 – 2016 1st set rHIVda developed, pilot testing in 8 sites
• 2017 DOH A.O. for rHIVda implementation
• 2018 Development of CrCLs to implement rHIVda
• 2019 First 15 CrCLs authorized to confirm HIV diagnosis
• 2020 Development of alternative rHIVda, more CrCLs developed
• 2021 26 CrCLs operational in conducting confirmatory HIV
diagnosis 11
History of rHIVda
• 2022 35 operational CrCLs conducting confirmatory HIV laboratory
diagnosis
• 2023 43 CrCLs authorized
rHIVda Expansion Project

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 rHIVda Study Protocol
Objective: To determine a good combination of screening tests (2 or 3) to be
used as a confirmatory HIV test algorithm in lieu of Western blot
algorithm ( to be done at the peripheral certified rHIVda Confirmatory laboratories, CrCLs)

Combination/s should be at par with the specificity of WB/current algorithm

Current algorithm(Centralized at NRL-SACCL):

1. (+) screening from referring labs
2. (+/-; +/+) 2 parallel screening tests (SACCL) +WB and or NAT

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rHIVda Study Protocol Results of 18 DOH FDA Registered Kits
Summary: HIV testing algorithm validation study (3/5/15)
Total samples panel tested
• Known (+) 204
• Known False (+) 624
Criteria for DOH- FDA No of kit tested
registration Machine-based immunoassay 8
4th gen (Ag-Ab) 6
= Sensitivity: 99% 3rd gen (Ab) 2
= Specificity: 99%
Rapid test (RDT) 10
Particle agglutination (Ab) 1
Direct solid-phase EIA (Ab,3rd gen) 1
(Ag-Ab, 4th gen) 1
Immunochromatography(ICT)
4th gen (Ag-Ab) 2 14
3rd gen (Ab) 5
rHIVda Study Protocol

No common
false+

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 rHIVda Study Protocol
Summary of Testing
Results Total FP Common FP
I. ImmunoAssay Tests IA1 96 21
IA2 83 57
IA3 75 33 Basis for selection of combination:
IA4 67 35
IA5 0 0 HISCL(CMIA) o least number of false (+) and
IA 6
IA7
12
96
10
47
Vidas (ELFA)
o Least number of
IA8 20 18 common/shared false (+)
II. Rapid Diagnostic Tests RDT1 19 15 PA 1/2 (Ab)
RDT2 10 6 Immunocomb HIV 1/2
RDT3 18 17 Select 3 RDTs and 2 IA kits
RDT4 14 10 SD HIV 1/2 (Ab)
RDT5 54 49
RDT6 12 11 Determine Ab
RDT7 18 14
RDT8 20 18
RDT9 52 49
RDT10 35 35

* known false (+)done 12/19/16

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 rHIVda Pilot Testing results
(Feb – July 2016, MSM, TG, PWD)
Pilot sites: used recommended 3 rapid diagnostic
test combination (SD, PA, Immunocomb)
NRL – SLH/SACCL: used 3 RDT+ 2IA+ WB + NAT
8 Pilot sites
3 SHC – Manila, Cebu,Davao
2 GO TH – VSSMC, SPMC
1 Sundown clinic – Klinika Bernardo
2 Pvt Clinic – LYFI (Anglo; Uni )

Target sample: 1000 initially reactive referral to

SACCL in 6 months
Total # referrals: 1462
182 (12.4%) – with previous confirmatory test 17
1280 tested for 6 test systems at SACCL
Result of rHIVda in 8 Pilot Sites
SD Bioline HIV 1/2 Ab;
Particle Agglutination Ab; Immunocomb Ab
vs
Gold standard
(Western Blot and NAT)

3/3 100% Specificity

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Validation Steps
Study participants
Voluntarysubmission
Test kits
Shared false
reactivity
evaluation
Test selection for
combination

Assess
diagnostic
performance

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 Goals of rHIVda
• Increase access to HIV confirmatory testing
• Reduce long waiting time & undiagnosed
LTFU cases
• Increase testing uptake to prevent fall outs in the
1st 95 of the HIV cascade of service.

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 New rHIVda Scheme

The HIV testing

facilities can now
refer to the different
CrCLs
Certified rHIVda Confirmatory
1,350 HIV laboratories Laboratories[CrCLs]

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Basic rHIVda Algorithm
All three (3) tests needs Test 1 Final Result:
to be REACTIVE for a
NON NONREACTIVE
POSITIVE confirmation.
REACTIVE (Negative Status)

Inconclusive
2020
status will be
Test2nd1ValidationTest 2 Test 3 Final Result:
referred to of HIV ICT
NRL- SACCL Assays REACTIVE
REACTIVE REACTIVE REACTIVE (Positive Status)

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rHIVda test kits
Test 1 (T1)
SD Bioline HIV 1/2 3.0

• NRL SLH/SACCL validated the rapid tests

to be used in the rHIVda.
• The combination is at par with the
specificity of the Western Blot Algorithm. Test 2 (T2)
Alere Determine HIV 1/2

• Validation study with WHO & NRL Aus.

Test 3 (T3) Test 3 (T3)

Chembio HIV 1/2 Stat-Pak Bio-Rad Geenius HIV 1/2 Confirmatory Assay
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 Current Validated rHIVda:
2017 Algorithm 2020 Algorithm-Present
Test 1 (T1) Test 1 (T1)
SD Bioline HIV 1/2 3.0 SD Bioline HIV 1/2 3.0

Test 2 (T2) Test 2 (T2)

Alere Determine HIV 1/2 Alere Determine HIV 1/2

Test 3 (T3)
Test 3 (T3)
Bio-Rad Geenius
Chembio HIV 1/2 Stat-
HIV 1/2
Pak
Confirmatory Assay

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Certified rHIVda Confirmatory Laboratory
(CrCL)
• A clinical laboratory compliant with rapid HIV diagnostic
algorithm (rHIVda) laboratory standards and technical
requirements set by NASPCP and NRL-SLH/SACCL
• Will perform three (3) HIV rapid tests in sequential
format.
• The idea is to release confirmed HIV Laboratory results
(POSITIVE & Negative) within the day.
• Other laboratories can also refer HIV samples to CrCLs

25
Certified rHIVda Confirmatory Laboratory
(CrCL) General Guidelines/Requirements
• License to Operate
• Quality Management docs (eg. SOPs, Quality Procedures,
etc.)
• Adequate space, trained staff and supervision
• Equipment availability

26
Certified rHIVda Confirmatory Laboratory
(CrCL) Roles and Responsibilities:
• Release accurate laboratory result on the same day of testing as
much as possible
• Develop, update, sustain, and strictly implement SOPs, job aides,
and QMS
• Participate in NEQAS
• Establish and maintain good coordination with other stakeholders
• Advocate logistical and human resource
• Submit reports regularly to CHD and Epidemiology Bureau

27
External Assessment
by WHO Consultant
(November 2015)

• Facility visit
• Direct Observation
• Interview

28
Result/Findings: WHO Consultant
Facility Testing process
• 2 out of 3 visited , laboratory • Technologist not following
inadequate size, manufacturer’s instructions; lack
• Workspace inadequate, testing, of supervision
documentation done in 1 table, source
of error Inadequate number of staff-
Documentation/Procedure/SOP- technical staff, too busy to attend
• Inadequate or none at all to proper documentation
Safety/Waste management Fast turn-over of staff, no
• Clean and dirty items not segregated orientation/ proper endorsement
• Infectious waste not regularly of new staff re rHIVda
collected- several months
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Result/Findings: WHO Consultant
QA of rHIVda Sites
Notwithstanding the very encouraging results of the pilot study, Quality assurance and
supervision of the rHIVda sites was lacking. There are minimum Quality requirements
documented for rHIVda sites, but none of the sites visited complied adequately with the
requirements.

Pathologist supervision appears erratic in its content and frequency. This may be
exacerbated by the “exclusion” of the SHCs from the usual supervisory structure (DOH
licensing).

AO No 2007-027A (Aug 28, 2008) – DOTS and SHCs exempted from DOH licensing, can
operate HIV testing lab
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 Presented by: Médecins Sans Frontières
(MSF); the Institute of Tropical Medicine;
ministries of health in Malawi, Myanmar
and Viet Nam; and the United States
Centers for Disease Control and
Prevention

Key information: Multiple reports of misdiagnosis and poor testing practices

- misdiagnosis of HIV-positive status from programme setting and external quality assessment
schemes (range: 0.7–10.5%) in Burundi, the Democratic Republic of Congo, Ethiopia, India,
Malawi, Mozambique, Myanmar, Uganda, Viet Nam and Zambia
- In some instances, over 2 years elapsed between misdiagnosed HIV-positive status and a
subsequent retest identifying the patient as HIV-negative.
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 Common Issues and Errors

• difficulty reading weak reactive lines;

• not using a validated national testing algorithm or WHO recommended testing strategy;
• poor training, support and supervision of testers;
• potential cross-reactivity (i.e. between tests and due to factors at the patient and environmental
level);
• reading test results before the reading time (i.e. minimum incubation period) was also
mentioned in relation to increased rates of false-negative results; and
• specimen mix-ups caused by batching of testing and deviations from manufacturer instructions
and standard operating procedures, such as incorrect use of test cards, which may lead to
cross-contamination of specimens (e.g. tests not separated from the 10-test card).
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WHO/HIV/2015.33 @WHO 2015
Authors: Johnson C., Fonner V, Sands A, Tsui S, Wong V, Obermeyer C, & Baggaley R

• Poor quality HIV testing Outcome: Misdiagnosis

Limitation of assay
Operator-related factors
Facility-related factors
inappropriate storage of reagents
workload: high client- overburdened staff
low client – poor proficiency of staff
Lack of supervision
• Late stage infection (Tanzania)
Participants encouraged WHO, ministries of health, implementing
partners and donors to prioritize funding to support quality testing
through adoption of quality systems at all testing sites, as well as
further study to document testing practices, measure the extent of
misdiagnosis of HIV status, and investigate why testers do not follow
national and site-level standard operating procedures or manufacturer
instructions.

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12 Elements – Quality System

• Personnel – adequate number; training; continuing education;

supervision
• Facility – adequate space; conducive working environment;
maintenance; equipment
• Management support – availability of supplies and reagents at
all times
• Quality Manual – procedures; guidelines; policies; documents,
records, worksheets
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No. Region Name of Facilty
1 CAR Baguio General Hospital and Medical Center
2 I Ilocos Training and Regional Medical Center
3 Region 1 Medical Center
4 Mariano Marcos Memorial Hospital and Medical
Center
4 II Cagayan Valley Medical Center
5 III Jose B. Lingad Memorial Regional Hospital
6 Bataan General Hospital and Medical Center
7 Dr. Paulino J. Garcia Memorial Research and
Medical Center
8 Bulacan Medical Center
9 James L. Gordon Memorial Hospital
10 Tarlac Provincial Hospital
11 CALABARZON Batangas Medical Center
12 Ospital ng Biñan
13 Laguna Medical Center
14 IV B Antipolo City Health Office Clinical
15 V Bicol Medical Center

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No. Region Name of Facilty
16 MIMAROPA Ospital ng Palawan
17 Western Visayas Medical Center
18 VI Corazon Locsin Montelibano Memorial Regional
Hospital
19 Dr. Rafael S. Tumbokon Memorial Hospital
20 VII Vicente Sotto Memorial Medical Center
21 VIII Eastern Visayas Medical Center
22 Klinika Bernardo Clinical Laboratory
23 Philippine General Hospital
24 Pasig City Clinical Laboratory
25 NCR Marikina City Public Health Laboratory
26 Research Institute for Tropical Medicine
27 Love Yourself, Inc.
28 Valenzuela Medical Center
29 Sta. Ana Hospital
30 San Lazaro Hospital
31 Victoriano Luna Medical Center
32 Manila Public Health Laboratory Department
33 Las Pinas General Hospital & Satellite Trauma Ctr

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No. Region Name of Facilty

34 IX Zamboanga City Medical Center

35 X Northern Mindanao Medical Center
36 X Mayor Hilarion A. Ramiro Sr. Medical Center
37 Southern Philippines Medical Center
38 Davao Reproductive Health and Wellness Center
XI
39 Davao Regional Medical Center
40 SOCCSKSARGEN Cotabato Regional Medical Center
41 Caraga Regional Hospital

42 CARAGA Adela Serra Ty Memorial Medical Center

43 Butuan Medical Center

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Summary of CrCLs & Location:

• Luzon: 12 CrCL in NCR,

• 16 CrCLs other provinces
• Visayas: 5 CrCL
• Mindanao: 10 CrCL
• Total functional CrCL: 43

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NCR
41
42
rHIVda Expansion
All HIV Certified To increase
Testing rHIVda access to
Clinical Confirmatory confirmatory
Laboratories Laboratories testing
[1,351] [CrCLs] &improve HIV
Care Cascade

43
 rHIVda Expansion
• Training of Trainors for Regional counterparts
All HIV Testing CLs to • rHIVda Training for RMTs, Pathologists
become CrCLs • Integrated rHIVda Proficiency Training for RMTs

Verification/Validation of • Study protocol development ongoing discussion with CDC-USA,

rHIVda for general DOH EB before submission to Ethics Review Committee
population • Pregnant women, OFW, others without known risk exposure

• Initial discussions of concept proposal between NRL SACCL, DPCB

Decentralization of Early & CDC-USA
Infant Diagnosis

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Steps in Acquiring rHIVda as Add-on Service:

Add-on Service
rHIVda Training rHIVda EQAS Application &
Approval

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Steps in Acquiring rHIVda as Add-on Service:
1. DPCB provides list of scheduled trainees per
training batch to NRL SACCL
2. SACCL conducts rHIVda Trainings and provide
rHIVda self-assessment tool to clinical laboratories
3. Excellent rHIVda EQAS score, retraining if 2 failures
4. Compliance to DOH issuance of LTO with add-on
rHIVda service.
5. Installation of eHARP by Epidemiology Bureau-DOH
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 WAYS FORWARD
• Regular coordination of stakeholders for ‘project rHIVda scale-up
plan’: DPCB, HFSRB, EB, SACCL, Regional Coordinators and
concerned clinical laboratories for the implementation of the rHIVda
Action Plan
• Trained Trainors /Regional Counterparts will roll-out of rHIVda
trainings in the region and mentor CrCLs
• Hired rHIVda coordinator to facilitate HFSRB & SACCL activities
• Implementation & regular updating of Regional Action Plans
• Logistics preparation & distribution of test kits
• Costing for maximum allowable fees proposal

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 WAYS FORWARD
• Advocate for quality laboratory testing with Heads of Laboratories & RMTs
• Monitor rHIVda performance & Continue validating new algorithms [data-
driven decision-making]

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Thank you !

Website: www.nrlslhsaccl.com.ph
email: [email protected]
Tel No: 632-53109528/29;
632-87323776-79 loc 207
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Fax No: 632-87114117