ritm anniv2011
TRANSCRIPT
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Rossana A. Ditangco, MD FPCP FPSMIDHead, AIDS Research Group Research Institute for Tropical Medicine
Alabang Muntinlupa City
Drug resistance monitoring amongFilipino HIV infected patients
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Number of HIV/AIDS Cases Reported in the Philippines by
Year, January 1984 to February 2011 ( N=6,326)
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Management of confirmed
HIV/AIDS
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GOALS:
prompt treatment of HIV relateddiseases
prevention of HIV related diseases
control of HIV infection
restoration of immune status
provision of psychosocial support
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Population-level effect of HIV on adult
mortality and early evidence of reversal
after introduction of antiretroviral therapy
in Malawi
Andreas Jahna et al
Reduction of AIDS related death decreased by 35%
Lancet . 2008 May 10; 371(9624): 1603±1611
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Universal access to AIDS treatment: targets and challenges
http://www.avert.org/universal-access.htm
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Benefit of early treatment
Protection from AIDS
related death
Lower risk of NON-
AIDS related death
Lower risk of
transmission
Potential benefit of early
treatment
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When to start treatment
WHO 2006
Clinical stage IV
Clinical stage 3
CD 4 not
available
CD4 T cell < 200
consider >200
and < 350 andclinical stage 3
WHO 2010
Clinical stage IV
Clinical stage 3
CD 4 notavailable
CD4 T cell < 350
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Limitations ART
Not curative
Short term and longterm toxicities
HIV drug resistance
Limitations ART
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Philippine scenario
0
200
400
600
800
1000
1200
1400
2006 2007 2008 2009 2010 2011
No of persons on ARV 2006- March 2011
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Requirements for safe and effective
use of ARV in roll out program
Supply
Infrastructure ± monitoring treatment
response and toxicity
Human resource ± training (ART,
adherence counseling)
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Real scenario in roll out program
Need to start ART
Training/experience
Need to start ART
Training/experience
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Strategy for safe and effective use of
ARV in roll out program
- local guideline
simple regimen
bulk purchase ± lower cost
less training needed
preserve limited 2nd
line
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1st line Unit cost Cost per day Cost per month Cost per year
3tc150mg/AZT
300mg
8.00 16.00 480
Nevirapine200mg 3.00 6.00 180
Total per months 660 7920
Tenofovir200mg 17.00 17.00 510
3tc 150mg 3.00 6.00 180
Efavirenz600mg 7 7.00 270
Total per month 960 11520
Cost of 1st line cART
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2nd line Unit cost Cost per day Cost per month Cost per year
3tc150mg/AZT
300mg
8.00 16.00 480
Lopinavir/rit 18.00 72.00 2160
Total per months
2640 31680
Tenofovir200m
g
17.00 17.00 510
3tc 150mg 3.00 6.00 180
Lopinavir/rit 18,00 72.00 2160
Total per month 2850 34200
Cost of 2nd line cART
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Adherence Impacts HIVAdherence Impacts HIV--RelatedRelated
Mortality and AIDS ProgressionMortality and AIDS Progression*1*1
*Prospective, observational study of 950 ART-naive patients treated with triple-
combination therapy; adherence was estimated by prescriptions dispensed.
1. Hogg et al. 7th CR OI 2000. Abstract 73.
For every 10%
decrease in
adherence
1.17 times higher likelihood
of progression
to AIDS
and/or death
5
16% increase in
HIV-related mortality
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FIRST LINE FOREVER!!!
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Philippine scenario
HIV drug resistance
HIVDR program
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Prevention of HIV drug resistance through
enhanced adherence and treatment
monitoring program - target: physicians and patients
- launched February 2010
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The goal of this project is to establish a MECHA NISM for
enhancing and monitoring adherence and for monitoringHIVDR within an ART scale up program.
objectives:
to enhance adherence among patients enrolled in the
treatment program to develop a mechanism on patient enrolment and
monitoring of treatment adherence
to develop a mechanism for monitoring virologic failure andemergence of HIVDR among patient enrolled in the ARV
treatment program
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Specific activities:
training of healthcare workers on treatment guideline
and adherence counseling
development and distribution of physician guide on
adherence counseling
development and distribution of IEC materials on
ARV for patients establish mechanism for timely pick up of ARVs
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Specific activities:
utilization of patient enrollment forms
utilization of adherence evaluation form
SOPs on patient enrolment (especially for patients to bemanaged by attending physicians outside of the treatmenthubs) and how to access ARVs from the treatment hubs
regular CD4 and viral load testing based on established localguideline
HIVDR testing among patients with virologic failure
development and utilization of database of enrolled patients
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Philippine scenario
Treatment hubs
ARV
-Trained (ART, adherence)
-NGO
-CD4 (5)
-VL (2)
-HIVDR (1)
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Treatment Hub
LUZON VISAYAS
San Lazaro Hospital (SLH) Bicol Regional Training
and Teaching Hospital
(BRTTH)
Vicente Sotto Sr .
Memorial Medical Center
(VSSMMC)
Research Institute for Tropical
Medicine (RITM)
Jose B. Lingad Memorial
Medical Center
(JBLMMC)
Western Visayas Medical
Center (WVMC)
Philippine General Hospital
(PGH)
Cagayan Valley Medical
Center (CVMC)
Corazon Locsin
Montelibano Memorial
Regional Hospital
(CLMMRH)
MINDANAO
Ilocos Training ang Regional
Medical Center (ITRMC)
Davao Medical Center
Baguio General Hospital and
Medical Center (BGHMC)
Zamboanga City Medical
Center
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Current ARV MedicationsNR TI
Abacavir (AB
C) Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (AZT,
ZDV)
NNR TI
Delavirdine (DLV)
Efavirenz (EFV)
Etravirine (ETV)
Nevirapine ( NVP)
PI
Atazanavir (ATV) Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)rit
Nelfinavir ( NFV)
Ritonavir (RTV)
Saquinavir (SQV)
Tipranavir (TPV)
Fusion Inhibitor
Enfuvirtide (E NF, T-20)
CCR5 Antagonist
Maraviroc (MVC)
Integrase Inhibitor
Raltegravir (RAL)
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Recommended regimen
First line regimen: NNRTI- based (2 NRTI + 1 NNRTI)
First line NRTIs : Zidovudine (AZT) + Lamivudine
(3TC)
Alternative first line NRTI :
a. Tenofovir (TDF) + Lamivudine (3TC)
b. Stavudine (d4T) + Lamivudine (3TC) - when TDF and
AZT are contraindicated
First line NNRTI: Nevirapine ( NVP)
Alternative first line NNRTI :
Efavirenz (EFV) - for patients with hypersensitivity to
nevirapine and/or taking rifampicin. EFV is contraindicated
in pregnant patients.
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Recommended regimen
S econd line regimen: 2 NRTIs + Lopinavir/ritonavir
(LPV/r )- AZT + 3TC + LPV/r if previously on TDF
- TDF + 3TC + LPV/r if previously on AZT or d4T
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HIV drug resistance testing Genotyping*
Phenotype
HIV DR databases ± IAS, Stanford,WHO
- subtypeB
, non subtypeB
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How are we doing so far?
Is the recommended first line effective?
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TREAT ASIA STUDIES TO EVALUATE
DRUG RESISAT NCE (TASER )
208 patients enrolled (April 2008)
-202 treatment naïve
-6 treatment experienced
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TREAT ASIA STUDIES TO EVALUATE
DRUG RESISAT NCE (TASER )
208 patients enrolled (April 2008)
-202 treatment naïve
- 192 with available baseline VL
median 202,915 (<46-6,099,010)R NA
copies/ml plasma
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TREAT ASIA STUDIES TO EVALUATE
DRUG RESISAT NCE (TASER )
208 patients enrolled (April 2008)
-202 treatment naïve
144 on 12th month follow-up
117 VL results available
113 (97%) <10,000
110 (94%) <1.000109 (93%) <400
85 (73%) undetectable
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TREAT ASIA STUDIES TO EVALUATE
DRUG RESISAT NCE (TASER )
208 patients enrolled (April 2008)
-202 treatment naïve
58 patients on 24th month follow-up
41 with viral load results
34 (83%) undetectable
37 (90%) < 400
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TREAT ASIA STUDIES TO EVALUATE
DRUG RESISAT NCE (TASER )
208 patients enrolled (April 2008)
-6 treatment experienced
baseline VL
5,822-471,483 R NA copies6 patients on 12th month follow-up
VL available 5 patients
3 undetectable
2 <4004 patients on 24th month- VL available 2 patients
2 patients VL < 400 coipies
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HIV drug resistance results
- based onWHO list of RAMTreatment naïve at baseline (amplified)
12/103 (12%) ±at least 1 HIV RAM
PIs- 7/79 (9%) ± at least 1 PI RAM
6/79 (6%) ± one mutation
1/79 (1%) ± 3 mutations
D30 N, L90M (2), I84V (2), M46I (3), F52Y
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HIV drug resistance results
- based onWHO list of RAMTreatment naïve at baseline (amplified)
12/103 (12%) ±at least 1 HIV RAM
NRT1 5/103 (5%) at least 1 RAM
3/103 (3%) w/ 1 RAM
1/103 (1%) w/3 RAM , 1/103 (1%) with 4
RAMT215Y, M41L(2), D67 N (2), M184V (2),
K219 N, K 65R, L210 N
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HIV drug resistance results
- based onWHO list of RAMTreatment naïve at baseline (amplified)
12/103 (12%) ±at least 1 HIV RAM
NNRT1 2/100 (2%) w/ 2 RAM
Y181C, G190A
K101P, G190A
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patient pi major nrti nnrti
R03-066 None M184V, L210W, T215Y K103N
R04-020 None L74I, M184V, L210W,
T215Y
Y181C,
R04-AMB None M41L, L74V, M184V,
L210W, T215Y
Y181C
R06-RBP None K65R, M184V Y181C
R09-STA None D67N, K70E L74I
M184V
V106M, Y181C,
G190A,
Treatment experienced (6/7)
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Future directions:
Patient adherence-counseling, monitoring
HCW- training, monitoring
Stigma and discrimination-self -isolation, familycounseling, communityeducation, health facilities,workplace
Local data- HIVDR,affordable monitoring toolsand algorithms
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Maraming Salamat Po at
INGAT LAGI!
(first line forever)