Increasing access to HIV treatment through clinical research

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Increasing access to HIV treatment through
clinical research

• Theshinee Chuenyam
• HIV-NAT Thailand
• September 2002

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History of HIV-NAT

• Vision of
• Praphan Phanuphak Thailand
• David Cooper - Australia
• Joep Lange The Netherlands

• Meeting in Phuket, Thailand 1995
• Set out to
• Create a centre of excellence for clinical trials
  in Asia
• With international collaboration
• To improve access to treatments for PLHA

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Partners

• Thai Red Cross AIDS Research Centre Bangkok -
  Prof. Praphan Phanuphak
• National Centre in HIV Epidemiology and Clinical
  Research Sydney - Prof. David A. Cooper
• International AIDS Therapy Evaluation
  CentreAmsterdam - Prof. Joep. M.A. Lange

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HIV Netherlands Australia Thailand Research
Collaboration
IATEC Amsterdam
TRCS Bangkok
Partners
NCHECR Sydney
NCHECR Sydney
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Mission and Objectives

• Conduct clinical studies according to good
  clinical practice (GCP) guidelines
• Improve access to antiretroviral therapy for
  HIV-infected people in Thailand
• Educate and train healthcare workers

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Milestones
1995 HIV-NAT concept 1996 start of
operations 1st patients enrolled on
study 1997 1st presentations at international
meetings 1998 1st Bangkok symposium in HIV
medicine UNAIDS collaborating centre 1999 new
building and facilities 2000 1st
publications 2002 approximately 1,200 patients
on studies
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1996 - Started with one room
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1999 - HIV-NAT building

• Donated by Thai Red Cross
• Renovated with support from pharmaceutical
  industry
• Administration
• Doctors nurses
• Pharmacy
• Patient treatment facility

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2002Thai Red Cross AIDS Research Centre
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What makes a Clinical Trial unit
Leaders
Team
Doctors, nurses, Statistician, IT Lab.
technologists
Commitment Scientific expertise
Clinical Trial Unit
Infrastructure
Administration
Funding
Links to hospitals Links to VCT Lab. facility
GLP Storage system Security back up
Secretary Financial Office assistants
Industry Research Grant Government
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Sponsorships Partners

• Pharmaceutical industry
• Funding to conduct studies
• antiretrovirals
• Ministry Public Health Thailand
• Ethics approval
• Access to hospital clinics
• Government Pharmaceutical Organization Thailand
• Antiretrovirals
• US National Institutes of Health
• Trials support
• Educational support (sponsor of Bangkok
  Symposium on HIV medicine)

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Sponsorships Partners

• International partners in Australia The
  Netherlands
• Some physicians salaries
• Research advice
• Connections to other funders
• Other foundations
• Education (amFAR)
• Regional training (Fogarty Institute)

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Learning by doing

• HIV-NAT studies
• 1st study supported by pharmaceutical industry
• Local level
• Success led to other industry support
• Local level
• International level
• Multinational studies
• Invited to join international network
• Vanguard (HIV-NAT 004) NIH sponsor
• Others followed

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Constraints Solutions

• Industry funding limited
• All studies have to end
• What happens then?
• ARV support after studies finish - a major
  challenge
• Growing infrastructure needs
• Personnel
• Physical space
• IT
• Statistical expertise

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Constraints Solutions

• Some solutions to continued drug access
• Post study drug supply
• Rollover studies (001 ? 1.1 ? 1.2 ? 1.3 ? 1.4)
• Same group of participants on study for 5 years
• Access to free ARV and free monitoring
• HIV-NAT drug fund
• 2 million baht plus annual endowment from HIV-NAT
  funds
• Patient co-pay basis
• Independent social worker assessment of ability
  to pay

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Constraints Solutions

• Some solutions to continued drug access
• Ministry of Health co-pay scheme
• MoPH buys efavirenz or indinavir/ritonavir
• Patient buys nucleoside backbone

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Ethics

• Two levels of ethical review
• MoPH
• Hospital ethics committees
• Ethics guidelines based on
• International rules
• GCP / ICH guidelines
• Adapted to cultural sensitivities
• Community advisory board being established

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Links with Healthcare Services

• Thai Red Cross Anonymous Clinic
• Chulalongkorn Hospital
• Community Groups such as
• Wednesday Friends Club
• HIV-NAT physicians are primary care providers
  for most study patients

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HIV-NAT Studies

• HIV-NAT initiated
• designed by HIV-NAT
• relevant to Thailand region
• Pharmaceutical industry studies
• HIV-NAT part of multi national study
• new drug
• new formulation
• FDA registration
• Pharmacokinetic studies
• Basic science
• Vaccines

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Study timelines at HIV-NAT
010
T-20 PK
009
HIV/Hep B/C
D4T ER
007
003
002
001
001.1
001.2
001.3
001.4 (STI)
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Locations
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HIV-NAT participants income
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HIV-NAT participants education
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What HIV-NAT has achieved (1996-2002)

• 1,200 patients on ART for as long as 5 years
• exceptional adherence to ART
• HIV clinical trials to GCP standards
• international recognition as a model for clinical
  research in the developing world

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What HIV-NAT has achieved

• Infrastructure
• patient facilities ?
• adequate space for personnel ?

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What HIV-NAT has achieved

• Competency of HCW
• on the job training
• regular clinical updates
• GCP training
• weekly journal club

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What HIV-NAT has achieved

• Drug storage
• Secure
• Temperature controlled
• Separate shelves per study
• Computerised tracking

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What HIV-NAT has achieved

• good clinical practice

• good laboratory practice
• Pharmacokinetic facility

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What HIV-NAT has achieved

• promote cultural sensitivity and awareness

• letting go

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What HIV-NAT has achieved

• Human resources
• MDs and nurses
• lab personnel
• pharmacists
• data managers

• admin staff
• security
• PLWHA

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Key issues - joining a clinical trial

• Why do patients want to join trial?
• access to care / to ARV
• What about discrimination?
• privacy / education / still work
• Can patients afford to buy medicine?
• Do HIV-NAT patients pay for medicine?
• Who is selected to join HIV-NAT trials?
• Men and women
• Family groups
• Why do people not join HIV-NAT trials?

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Key issues counseling and support

• Pre and post-test counselling
• HIV-NAT linked to Anonymous Clinic
• Ongoing counselling
• Prevention of transmission
• Adherence to treatment
• Maximise quality of life

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Key issues - ARVs

• Drugs from industry
• Drugs produced generically in Thailand
• How are drugs selected
• Sponsor needs
• Availability
• Research question
• Cost

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Key issues - OIs

• All HIV-NAT patients receive OI prophylaxis
• MoPH guidelines
• OI treatment by hospital referral

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Key issues - monitoring

• Fully sponsored study every 3 months
• CD4
• Viral load
• Toxicity monitoring (CBC and chemistry)
• Resistance testing
• Follow-up studies (limited sponsorship) 6
  months
• CBC and chemistry
• CD4 and VL
• Clinical assessment at every visit

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Key issues - adherence

• Adherence counseling
• Every visit
• Nurses
• Doctors
• Pharmacist
• High level of adherence achieved
• Questions
• How many doses missed past 7 days?
• How many doses missed since last visit?
• Correct timing of doses?

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Key issues future challenges

• Treatment of children
• Treatment of families - MTCT
• ARV resistance
• ARV failure - salvage regimens
• Side effects

ARV access
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Monthly Drug Costs (Baht) in Thailand in Year 2001
ARV access
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ARV access
Lowest monthly costs of triple ARV combinations

• Triple combination price / month US
• d4T / 3TC / ddI THB 2700 60
• d4T / 3TC / IDV THB 7260 161
• d4T / 3TC / NVP THB 1200 30

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Acknowledgments - key supporters

• Faculty of Medicine, Chulalongkorn University
• NIAID, NIH, USA
• AIDS Division, MOPH, Thailand
• Government Pharmaceutical Organization (GPO)
• Thai Red Cross Society
• Bayer Boehringer-Ingelheim
• Bristol-Myers Squibb GlaxoSmithKline
• Merck N V Organon
• Roche

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Treatment works