Practical AntiRetroviral Therapy in Vietnam and Access to Care

1
Practical Anti-Retroviral Therapy in Vietnam and
Access to Care

• Eric Krakauer, MD, PhD, Director
• William Rodriguez, MD, Senior Clinical Advisor
• Vietnam-CDC-Harvard Medical School AIDS
  Partnership (VCHAP)
• Division of AIDS / Depts. of Social Medicine
  Medicine
• Harvard Medical School
• June 27, 2003

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Outline

• Why antiretroviral (ARV) therapy?
• Antiretroviral treatment guidelines
• Choosing an ARV regimen for Vietnam
• Clinical issues specific to Vietnam
• Safe storage and handling of ARVs
• Adherence to ARV regimens
• Access to ARVs
• Patient selection criteria
• ARV procurement

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Why antiretroviral (ARV) therapy?
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Causes of Death Among Adults United States,
1982-1998
Effective Antiretroviral Therapy
HIV first identified
40
Unintentional
injury
35
Cancer
30
Heart disease
25
Suicide
20
Deaths per 100,000 Population
HIV infection
15
Homicide
10
5
Chronic liver
disease
0
Stroke
82
84
86
88
90
92
94
96
98
Diabetes
Year
Preliminary 1998 data
Source Centers for Disease Control, 2001
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Benefits of ARV Therapy

• Improve quality of life
• Prevent opportunistic infections
• Prevent disease progression
• Reduce stigma
• Increase incentive for HIV testing
• Reduce transmission to others
• TREATMENT IS PREVENTION

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Antiretroviral Treatment Guidelines

• Vietnam MOH Guidelines on HIV/AIDS Therapy 2000
• Two drug ARV therapy for CDC Class B2 disease
• Triple therapy with indinavir
• Thai National Guidelines for Clinical Management
  of HIV Infection in Children and Adult sixth
  edition 2000
• 2 NRTIs 1 NNRTI
• 2 NRTIs 2 PIs
• Dual regimens not recommended
• WHO Scaling Up Antiretroviral Therapy in
  Resource Limited Settings Guidelines for a
  Public Health Approach 2002

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WHO Recommended Treatments

• 3-drug therapy
• 2 NRTI 1 NNRTI
• AZT 3TC nevirapine
• (or efavirenz)
• 3 NRTI
• AZT 3TC abacavir
• 2 NRTI PI
• AZT 3TC nelfinavir
• AZT 3TC lopinavir, indinavir or saquinavir
  ritonavir

2-drug therapy ? No longer advocated -- much
less effective -- drug resistance -- cheaper
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30
25
Monotherapy
No therapy
of patients progress- ing
20
Dual therapy
15
10
Triple therapy
5
0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
months
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Choosing an ARV Regimen for Vietnam

• Criteria
• High potency
• Ease of adherence
• Infrequent dosing (qd or bid)
• Low pill load per dose
• Lack of dietary restrictions
• Minimal toxicity
• Minimal drug interactions
• Minimal risk of developing resistance
• Low cost
• Avoid dosing by weight d4T, ddI, ?Indinavir
• Keep open future ARV options

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• Other clinical issues in Vietnam
• Hot climate
• Volume depletion conducive to nephrolithiasis
  with Indinavir
• Unreliable cold chain?
• PIs Ritonavir (r), Lopinavir/r, Saquinavir

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16 drugs are available for HIV therapy
Reverse transcriptase inhibitors
(10) Nucleoside analogues (NRTIs) Non-nucleosides
(NNRTIs) zidovudine nevirapine stavudine
delavirdine lamivudine efavirenz zalcitabine
didanosine abacavir Nucleotide tenofovir
Protease inhibitors (6) amprenavir indinavir saqui
navir nelfinavir ritonavir lopinavir
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Several combination drugs are also
available AZT 3TC Combivir, Duovir
(Cipla), Lamzidivir (Stada MST) AZT
3TC nevirapine Duovir-N (Cipla) AZT 3TC
ABC Trizivir (GSK) d4T 3TC nevirapine
Triamune, GPOvir (Thailand)
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Recommended 1st Line Regimen

• AZT 3TC nevirapine
• If possible, screen for elevated AST ALT, Hep B
  C. If positive, use alternative regimen if
  possible.
• If possible, monitor AST ALT q month x 3
  months.
• Alternatives
• AZT 3TC efavirenz (avoid in pregnancy)
• AZT 3TC nelfinavir

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Safe Storage and Handling of ARVs

• Given great demand, risk of black market
• Need national guidelines on
• Safe storage
• Accountability of clinicians

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Adherence to ARV Treatment

• Base ARV treatment on model of TB treatment
• Close collaboration with National TB Program
  (NTP)
• Use NTP infrastructure
• Adherence counseling and monitoring for all
  patients (DOT)
• HIV/TB co-infection treatment program

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Adherence to ARV Treatment

• Social Supports
• Community health workers (paid, volunteer,
  faith-based)
• Home Health Aids
• DOT
• Meals
• Child care
• Palliative care
• Bereavement support
• Financial support
• School tuition, food, clothes, housing
• Include cost of social (adherence) supports in
  planning ARV treatment program

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Adherence
Percentage of Medication Taken
lt80
80 to 95
95 to 99
100
50
40
Percent of patients with viral load lt500 copies
30
20
10
0
2 Months
6 Months
Haubrich RH, et al. AIDS 1999131099-107.
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Access to ARV Treatment

• Patient selection criteria
• ARV drug procurement

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Patient Selection for Pilot Program
WHO Guidelines for Adults Stage I disease
(Asymptomatic) ? All patients with CD4 count
lt200 Stage II or III disease (Symptomatic HIV
disease) ? All patients with CD4 lt 200 or
Total lymphocyte count lt 1200 Stage IV
disease (AIDS) ? All patients
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Patient Selection for Pilot Program

• Four principles
• Sickest patients now
• Patients most likely to become much sicker soon
• Patients most likely to benefit from available
  drugs
• Patents most likely to take the drugs
  effectively (adherence)

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Identifying Sickest Patients

• The Farmer criteria
• Recurrent OIs difficult to manage with
  antibacterials or antifungals
• Chronic enteropathy with wasting
• Unexplained severe weight loss
• Severe HIV-related neurologic complications
• Severe leukopenia, anemia or thrombocytopenia

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Patient Selection for Pilot Program

• Sickest patients without medical or psycho-social
  contra-indications?
• Unable to take pills
• High risk of severe toxicity with available
  regimens
• Highly unlikely to be adherent
• Unwilling to participate in DOT
• Ante-natal women entering PMTCT program?
• Peer educators?
• Absence of active TB

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ARV Procurement

• Intellectual Property Rights (IPR)
• Agreement on Trade Related Aspects of
  Intellectual Property (TRIPS) 1994
• WTO Doha Declaration on TRIPS and Public Health
  2001
• TRIPS does not and should not prevent members
  from taking measures to protect public health
  and from promoting access to medicines for all.
• Drug patents
• Individual drugs
• Combinations
• US Presidential Executive Order 13155 (May 2000)
• Reaffirmed by USTR February 2001
• What does it all mean? Need clarification.

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ARV Procurement

• Quality Assurance (QA)
• WHO pre-qualification
• Time constraints
• Other modes of QA?
• Manufacturers in developing countries affiliated
  with western companies?
• In-country mass spectrometry?

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ARV Procurement

• Options for obtaining ARVs
• Importation of inexpensive generics with WHO QA
• Cipla, Ranbaxy 350 - 400 / patient/ year
• Best option for rapid start of pilot ARV
  treatment programs
• Compulsory licensing for domestic production as
  per TRIPS
• Takes time to produce quality assured product
• Negotiate low price with brand-name manufactures
  under threat of compulsory licensing (Brazil)
• Still quite expensive

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Outline

• Why antiretroviral (ARV) therapy?
• Antiretroviral treatment guidelines
• Choosing an ARV regimen for Vietnam
• Clinical issues specific to Vietnam
• Safe storage and handling of ARVs
• Adherence to ARV regimens
• Access to ARVs
• Patient selection criteria
• ARV procurement