ritm anniv2011

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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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- 192 with available baseline VL

median 202,915 (<46-6,099,010)R NA

copies/ml plasma

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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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58 patients on 24th month follow-up

41 with viral load results

34 (83%) undetectable

37 (90%) < 400

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-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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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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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)

Documents

ritm anniv2011