WHOAFRO HIV Drug Resistance HIVDR Monitoring Program

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TAP-RAP/RCCC meeting, Maputo, June 2006

• WHO/AFRO HIV Drug Resistance (HIVDR) Monitoring
  Program
• Laboratory Support
• for the HIV/AIDS Regional Program

Dr. Xiaohui YE Laboratory Technical Officer
WHO/AFRO
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Presentation Outline

• Background of the HIVDR and antiretroviral
  therapy (ART) in Africa
• Description of the laboratory involvement in the
  provision of HIVDR monitoring
• Highlight achievements, constraints, challenges
  and future perspectives in HIVDR monitoring in
  African Region

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Background of the HIVDR and ART in Africa
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Most current HIV-1 ARV drug regimens, HIVDR test
and interpretation were designed mainly based on
subtype B which are dominant in Europe and US,
while non-B subtypes HIV infection predominate in
Africa
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HIV genetic variability and ART
Variability Response
to ARV
HIV-2 Naturally
resistant to NNRTIs HIV-1 Group O
Naturally resistant to
NNRTIs HIV-1 Group M
Subtype F
Low susceptible to
NNRTI G
Low susceptible to PIs
A
Low susceptible to PIs
C Low
susceptible to PIs and NNRTI
D More resistant
to NVP than A in PMTCT H

N/A K
N/A

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ARV Selection Pressure and HIVDR

• When HIV treatment started, HIV medications will
  dramatically lower the amount of HIV in your body
  -- provided you take all your meds on time and
  your HIV isn't already drug resistant.
• Some HIV always survives, though, including some
  mutations

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laboratory involvement in the provision of HIVDR
monitoring

• Types of HIVDR tests
• Genotype tests -- look for specific mutations
  in the genetic structure of reverse transcriptase
  and protease region
• Phenotype tests -- measure the sensitivity of
  HIV to specific ARV
• WHO/AFRO HIVDR program
• Surveillance-- estimate frequency of HIVDR in
  untreated persons recently infected with HIV in
  specific geographic settings by using standard
  surveillance protocol
• Monitoring-- evaluate patterns of HIVDR
  mutations emerging with first line regimens in
  sentinel centers by using HIVDR monitoring
  protocol

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Achievements (1)

• 2002, Organize a meeting to develop the first
  protocol for HIVDR monitoring in the region
• Countries involved
• Uganda
• Côte divoire
• Senegal
• South Africa
• Partners CDC, IRD Montpellier
• WHO/AFRO, WHO/HQ

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Achievements (2)

• 2003, A phased implementation plan to initiate in
  2 countries Senegal, South Africa
• Discussion started with partners to get more
  findings to support countries
• MOU signed between WHO and International Atomic
  Energy Agency (IAEA)
• Participation of WHO/HIV ResNet meeting in
  designated / participating genotyping
  Laboratories

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Achievements (3)

• 2004, the first external quality assurance scheme
  (EQAS) for HIVDR testing was started in the
  Africa
• Reference laboratory IRD, Montpellier, France
• 4 participating laboratories
• Senegal CHU Le Dantec, Dakar
• South-Africa NICD (National institute for
  communicable diseases)
• Côte dIvoire RETROCI
• Botswana Harvard HIV reference laboratory
• 4 plasma samples testing subtypes/ CRF, mutation
  and VL
• Technique used in reference Lab----in-house
  protocol
• in participating
  Labs---- 2 Viroseq genotyping
• 
  2 in-house premers
• 2005, HIVDR EQAS
• 4 countries Cameroon IMPM/IRD, Yaounde

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Conclusions of EQAS 2004

• Amplification of the samples
• 4/4 subtype A 73908 copies/ml
• 1/4 subtype D 5140 copies/ml
• 3/4 CRF02-AG 3120 copies/ml
• 4/4 subtype C 9810 copies/ml
• Detection of mutations
• all major mutations detected,
• more discordances for minor mutations
• a major NRTI mutation in CQ4 detected from
  treatment naive patient in 1 laboratory
• Interpretation of mutations
• important discordances for certain samples
  according to algoritm used

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Conclusions of EQAS, 2005

• Amplification of the samples-- all positives
  amplified, negative sample was not amplified
• Detection of mutations-- all major mutations
  detected, more discordances for minor mutations
• Interpretation of mutations-- important
  discordances for certain sample according to
  algoritm used
• EQAS showed
• a good performance of the different Labs
• some Labs should do effort to improve the
  overall quality of sequence results by reducing
  the number of ambiguous bp designations

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EQAS for HIVDR monitoring in Africa
2004
2005
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Achievements (4)

• 2005, Organize a meeting on HIVDR monitoring ,
  Dakar, 18-20 April
• Discussed with CCEAC to develop a program for
  some Central Africa countries
• Organized briefing/missions to support the
  development of protocol for HIVDR surveillance
• To OCEAC (CAR, Chad, Congo, CAE, Gabon)
• To TAP project (Burkina Faso)
• Swaziland

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Countries with HIVDR monitoring data received in
AFRO
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Constraints

• Limited financial support to HIVDR monitoring in
  the region
• Lack of infrastructure for HIVDR monitoring in
  most of countries
• Inadequate numbers of laboratory staff trained in
  the countries

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Challenges

• Sustaining the level of financing that will
  guarantee optimal laboratory HIVDR monitoring
• Ensuring and maintaining a coordinated QA/QC
  system that will guarantee quality HIVDR
  monitoring
• Provision of technical support in HIVDR
  monitoring to the maximum of countries

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Future Perspectives

• Train laboratory staff in HIVDR monitoring
• Establish regional reference laboratories for
  HIVDR monitoring
• Re-dynamise a fully functional HIVDR monitoring
  network
• Develop a regional database on HIVDR monitoring
• Assist countries to have harmonized database for
  HIVDR monitoring

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Plan for HIVDR Monitoring WHO/AFRO, 2006

• CDC 4 countries --Tanzania, Kenya, Mozambique
  and Ethiopia
• OPEC 4 countries -- Burkina Faso, Swaziland,
  Uganda, and Zambia
• IAEA 5 countries -- Cameroon, Kenya, Ethiopia,
  South-Africa, and Uganda
• TAP 3 countries -- Ghana, Mozambique, and
  Burkina Faso
• EQAS 8 countries

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A vision without action is just a dream an
action without vision just passes time a
vision with an action changes the world.
-- Nelson Mandela
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THANK YOU