Title: Practical AntiRetroviral Therapy in Vietnam and Access to Care
1Practical 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
2Outline
- 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
3Why antiretroviral (ARV) therapy?
4Causes 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
5Benefits 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
6Antiretroviral 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
7WHO 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
830
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
9Choosing 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
10- Other clinical issues in Vietnam
- Hot climate
- Volume depletion conducive to nephrolithiasis
with Indinavir - Unreliable cold chain?
- PIs Ritonavir (r), Lopinavir/r, Saquinavir
1116 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
12 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)
13Recommended 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
14Safe Storage and Handling of ARVs
- Given great demand, risk of black market
- Need national guidelines on
- Safe storage
- Accountability of clinicians
15Adherence 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
16Adherence 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
17Adherence
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.
18Access to ARV Treatment
- Patient selection criteria
- ARV drug procurement
19Patient 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
20Patient 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)
21Identifying 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
22Patient 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
23ARV 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.
24ARV 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?
25ARV 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
26Outline
- 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