HIVAIDS in Thailand

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HIV/AIDS in Thailand

• Population of Thailand 65,444,371
• People died from HIV/AIDS 505,000
• People living with HIV/AIDS 570,000
• of adults living with HIV/AIDS 1.5
• Women living with HIV/AIDS 200,000
• Children living with HIV/AIDS 12,000
• Deaths due to AIDS per year 58,000
• Children who have lost their parents
• to AIDS 120,000

Source UNAIDS
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Development of Antiretroviral Treatment Services
in Thailand
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(No Transcript)
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ARV Therapeutic Options in Access to Care Program
( ATC 1) 2000-2001

• Patients must be naiive
• Limited quota
• ZDV/3TC NVP
• ZDV ddI NVP
• ZDV/3TC EFV
• d4T ddI EFV
• ZDV/3TC SQV RTV
• d4T ddI SQV RTV
• ZDV IND RTV
• d4T ddI IND RTV

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ARV Therapeutic Options in Access to Care Program
( ATC 2) 2002

• Patients must be naiive
• Limited quota
• ATC 1 ( limited cases)
• d4T 3TC NVP
• d4T 3TC EFV
• d4T 3TC IDV/R

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ARV Therapeutic Options in National Access to
Antiretroviral Program for PHA (NAPHA) 2004

• Opened Criteria for naive, alternative drugs for
  managing S/E, GPO-vir experienced
• No quota
• ATC 1 ( limited cases)
• d4T 3TC NVP
• d4T 3TC EFV
• d4T 3TC IDV/R
• AZT
• ddI

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Overall Case Uptake
SSO ARV
NAPHA
ATC 1
ATC 2
PMTCT
SSO Uptake Excluded Since 2004
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NAPHA data

• From 42,139 patients enrolled January 2000-March
  2005 (82.8 enrolled 2003-2004)
• 52.2 were male, and median age was 34.1 years
• At baseline, 49.3 had clinical AIDS, and median
  CD4 count was 46 cells/mm3
• Initial treatment included nevirapine- (90.2)
  and efavirenz-(8.1) based regimens
• At follow-up, 85.1 of patients remained on
  treatment (2.6 stopped ARVs, 5.4 were lost to
  follow-up, 6.2 died due to AIDS, 0.7 died not
  due to AIDS)

Courtesy from Sanchai Chasombat
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Services Coverage
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HIV/AIDS Laboratory Structures

• Anti-HIV every hospitals
• PCR- selected through
• medical sciences regional centers 12
• CD4 single platform / dual platform 102
• Viral Loads 27
• HIV Drug Resistance 7

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How do we define failure?

• Virologic failure
• Incomplete virologic response (VL gt400 copies/mL
  by 24 wks or gt50 copies/mL by 48 weeks)
• Virologic rebound (after suppression, recurrent
  viremia)
• Immunologic failure
• Failure to increase CD4 cell count by 25-50 over
  1st year
• Decrease to below baseline
• Clinical failure
• Occurrence/recurrence of HIV-related events
  (excluding immune reconstitution syndromes)

DHHS Guidelines, May 2006
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Correlation between VL and Duration of Treatment
P0.00, 95CI1.22-4.62
ODPC 7th Ubon
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Correlation between VL Response and Duration of
Treatment
NAPHA ODPC 7th Ubonratchathani Province 2005
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Correlation between Drug Resistance and Duration
of Treatment
Chi-square for linear trend 4.5 P0.03
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Mutations Selected by NNRTIs
103
181
188 190
Y
V
Multi-NNRTIResistance
106
188
L
M
Multi-NNRTIResistanceAccumulationof Mutations
L
V
Y
G
M
181
100
190
106
230
I
A
CI
SA
L
Y
K
Y
V
V
G
L
Nevirapine
100
103
106
108
181
190
188
I
AM
CI
A
CLH
I
N
Y
K
Y
P
Delavirdine
181
103
236
188
C
N
L
L
Y
K
Y
L
V
G
P
Efavirenz
100
103
108
181
190
188
225
L
N
I
CI
SA
I
H
Johnson A et al. Topics HIV Med
2003 www.iasusa.org
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Mutations Selected by NRTIs/ntRTIs (cont)
M
Zidovudine
NAMs
41
L
V
Stavudine
118
I
Didanosine
Zalcitabine
Abacavir
M184V
Lamivudine
Emtricitabine
K65R
Tenofovir
Johnson A et al. Topics HIV Med 2004
www.iasusa.org
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Multi-NRTI Resistance
Q151M
69i complex
Q
F
Multi-nRTIResistance 151 Complex
116
151
Y
M
Multi-nRTIResistance69 InsertionComplex
Multi-nRTIResistanceNAMs
Plus M184V whole class resistance
NAMs
41, 67, 70, 210, 215, 219, and 44,118
Johnson A et al. Topics HIV Med
2003 www.iasusa.org
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Mutations in HIV-1 RT Commonly Associated with
Resistance to NRTIs
Mark A. Wainberg Clin Care Option 2005
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Summary of Effects of Common Mutational Patterns
Mark A. Wainberg Clin Care Option 2005
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Duration of ARV and gt 3 NAM Mutation in NNRTI
Failure
RR 5.12 (95CI 1.035-25.316, p0.045) Courtesy
from Chetchotisakd P.
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Options for the Second Antiretroviral Regimen for
HIV-infected Patients Failing an Initial Regimen
of Fixed-dose Combination of Stavudine,
Lamivudine and Nevirapine

• 98 patients, mean ( SD) age of 35.2 6.3 years
• 63 of patients were males.
• Median (IQR) duration of ART prior to virological
  failure was 20 (13-28) months.
• Median CD4 cell count at the time of virological
  failure was 159 (105-248) cells/mm3.
• Median HIV RNA at the time of virological failure
  was 13,100 (5,090-54,700) copies/mL or 4.1
  (3.7-4.7) log copies/mL. .

Sungkanuparph, et al. CID 2007 44(3)447-52
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patients with 1 major mutation conferring drug
resistance to NRTIs, NNRTIs and PIs were 96,
95, and 0.
Sungkanuparph, et al. CID 2007 44(3)447-52
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The distribution of the frequency for each TAM
Sungkanuparph, et al. CID 2007 44(3)447-52
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The distribution of NNRTI-resistance mutations
Sungkanuparph, et al. CID 2007 44(3)447-52
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Drug-resistant mutations of patients with HIV RNA
lt4 (n44) vs. gt4 log (n54) at failure
P 0.041
P 0.763
P 0.105
P 0.008
P 0.031
P 1.000
Sungkanuparph, et al. CID 2007 44(3)447-52
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• Number of TAMs and HIV RNA Levels at Failure
  Detection.
• there was a trend toward higher HIV RNA level in
  patients who had 4 TAMs compared to that in
  patients without TAMs (p0.077).

P 0.418
P 0.661
P 0.743
P 0.077
Sungkanuparph, et al. CID 2007 44(3)447-52
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Factors associated with the occurrence of K65R
(multivariate analysis)
Sungkanuparph, et al. CID 2007 44(3)447-52
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Factors associated with the occurrence of Q151M
(multivariate analysis)
Sungkanuparph, et al. CID 2007 44(3)447-52
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ART Failure in UC

• Almost patients have 3TC and NNRTI resistance
  after failing an initial fixed-dose combination
  of d4T/3TC/NVP.
• TAMs, K65R and Q151M are frequently associated
  with high HIV RNA (gt4 log copies/mL) at
  virological failure. Therefore, when we detect
  virologic failure too late we would confront with
  more resistances.
• The mount of HIV-infected patients receiving ART
  is more than 80,000.
• How we monitor them for ART failure with the
  limiting resources.
• What are the second line for ART.
• Same problems with ART Failure in SSO more than
  33,000 receiving ART.

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Virologic Failure Treatment Options
DHHS Guidelines Oct 2006

• 2 NRTIs (based on resistance testing) PI (with
  or without low-dose ritonavir) (AII)

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NNRTI-based failure Early failureSecond-line
Treatment Regimens for Adults

• All drugs should be replaced

Cost Issue !! ??
Early failure
lt3NAMs M184V
TDF or ABC ddI LPV/r or SQV/r or ATV/r
d4T or ZDV 3TC NVP or EFZ
Change to
Modified from the Draft Scaling-Up
Antiretroviral Therapy in Resource-Limited
Settings, 2003
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NNRTI-based failure long-term failure !
Second-line Treatment Regimens for Adults

• All drugs should be replaced but it is not that
  simple !!

Cost, pills Issue !!
Long-term failure
gt3NAMs M184V
TDF or ABC ddI LPV/r/SQV or LPV/r/IDV
d4T or ZDV 3TC NVP or EFZ
Change to
Need further study
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Present Issues in HIV/AIDS Treatment and Care

• Early switching VS late switching of drug
  regimens
• Investment for the future or facing future
  bankruptcy?
• Second line treatment of ART
• Single-boosted PI plus recycle NRTIs VS Double
  Boosted PI.

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Present Issues in HIV/AIDS Treatment and Care

• Supporting infrastructures readiness
• Supporting technical networking
• Training to HIV professionals
• Clinical Research Networks
• Laboratory CD4, VL, Genotype, TDM
• Availability and external quality assurance
• Burnt out of existing HIV professionals
• Expanding supply, changing management approaches

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Increasing Primary Drug Resistance CDC Survey
1. Bennett D, et al. CROI 2002. Abstract 372 2.
Bennett D, et al. CROI 2005. Abstract 674
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Summary

• How many are resistant cases out there at
  present?
• Can we early detect with the existing system we
  have now?
• What are the appropriated second line regimens?
• What are the quality assurance for HIV/AIDS care?