TAP Program Mozambique DREAM, Treatment Acceleration Program Learning from the experiences gained and the challenges ahead November 30, 2006 TAP Program

TAP Program Mozambique TAP Program Mozambique DREAM, DREAM, Experience under the TAP:

ART regimen for PMTCT and PMTCT+

Treatment Acceleration ProgramTreatment Acceleration ProgramLearning from the experiences gained and the challenges Learning from the experiences gained and the challenges

aheadaheadNovember 30, 2006November 30, 2006

Leonardo Palombi and Maria Cristina Marazzi

The Central Question:Are optimal standards of care unsustainable?

816

2863

5037

6669

0

1000

2000

3000

4000

5000

6000

7000

2002 2003 2004 2005-2006*

Enrolled patients by year in MozambiqueTotal: 15,385

* March 2006

TAP Cohort

548

1592

26673062

0

500

1000

1500

2000

2500

3000

3500

2002 2003 2004 2005-2006*

Patients receiving HAART in Mozambique by year

TOTAL 7,869

* March 2006

TAP Cohort

DREAM FrameworkDREAM Framework

Nationwide Public Health program encouraging cooperation with Nationwide Public Health program encouraging cooperation with faith-based NGOs and local NGOs faith-based NGOs and local NGOs

Full package of care, free – of - charge: Full package of care, free – of - charge: Educational and social supportEducational and social support VCTVCT HAART (from late Feb 2002)HAART (from late Feb 2002) treatment of OI, STI, Malariatreatment of OI, STI, Malaria nutritional evaluation & supplementationnutritional evaluation & supplementation Mother & Child Prevention & Care (MCPC)Mother & Child Prevention & Care (MCPC) Overall Informatics ManagementOverall Informatics Management

run by Community of Sant’ Egidio, comprehensive agreement run by Community of Sant’ Egidio, comprehensive agreement with Ministry of Healthwith Ministry of Health

Training courses locally and internationally for M.D.s, Training courses locally and internationally for M.D.s, technicians, biologists, nurses, social workers, activiststechnicians, biologists, nurses, social workers, activists

The African patient profileThe African patient profile

•Malnourishment•TB•Malaria•Anemia•Parasitosis

•Poverty•Poor access to health centers

•HIV Clade C

People in sub-Saharan Africa on antiretroviral People in sub-Saharan Africa on antiretroviral treatment treatment

as percentage of those in need, 2002–2005as percentage of those in need, 2002–2005

20022003

2004

2005

7.2Source: WHO/UNAIDS (2005). Progress on global access to HIV antiretroviral therapy: An update on “3 by 5.”

Achieving AdherenceAchieving Adherence

Predisposing Cultural FactorsPredisposing Cultural Factors Increasing patient knowledge about the disease and treatment, etc. Increasing patient knowledge about the disease and treatment, etc.

Enabling – Organizational FactorsEnabling – Organizational Factors Free access to HAARTFree access to HAART and to OI treatment and to OI treatment

Reinforcing – Participative FactorsReinforcing – Participative Factors Employment of activists in the programmeEmployment of activists in the programme

Achieving AdherenceAchieving Adherence

77,4%

22,6%

<18,5>18,5

90,9%

9,1%

<18,5>18,5

Day Hospital of Machava (Matola, Mozambique)

BMI distribution patterns in 296 patients along 24 months

93,9%

6,1%

<18,5>18,5

18 months T1 BMI<18.5: 9.1%

6 months T2 BMI<18.5: 6.1%

Observation T0 BMI<18.5: 22.6%

70,3%

2,7%

27,0%

<88<10>10

91,2%

8,4%0,3%

<88 < 10>10


Hb levels in the same cohort

95,9%

4,1%0,0%

<88 < 10>10

HB<8: 2.7%HB<10: 27%

HB<8: 0.3%HB<10: 8.4%

HB<8: /HB<10: 4.1%

6,8%

93,2%

<400>400

< 400 copies/ml< 400 copies/ml >400 copies/ml>400 copies/ml

276276 2020


Viral load at the final observation

0

5

10

15

20

25

30

35

40

45

2002 2003 2004 2005 2006

TestEquipment

Cost of Viral Load (b-DNA) unit analysis by year

USD

Involving patients in the care process….

Mulheres para o dream

Major limitations of an Major limitations of an exclusively preventive approach exclusively preventive approach

- MTCT- MTCT High refusal and drop out High refusal and drop out

ratesrates Severe limitations Severe limitations

resulting from low access resulting from low access rate to health centersrate to health centers

Unsafe breastfeedingUnsafe breastfeeding Increased number of viral Increased number of viral

resistance mutationsresistance mutations No protection for mothersNo protection for mothers

23/704 (3.2%) 1 month after delivey

11/704 (1.5%) 1-6 months

after delivery

Refused: 83/999 (8.2%)

65/916 (7.1%)Before delivery

Refusal - Drop outRefusal - Drop out

Accomplished the protocol: 81.2%)

TRIPLE ANTIRETROVIRAL PROPHYLAXIS ADMINISTERED DURING PREGNANCY AND AFTER DELIVERY SIGNIFICANTLY REDUCES

BREASTMILK VIRAL LOAD -A STUDY WITHIN THE DREAM PROGRAM –

Marina Giuliano, MD,* Giovanni Guidotti, MD, Mauro Andreotti, B.Sc.,* Amerigo Assane, XX, + Maria F.

Pirillo, B.Sc.,* Paola Villani, B.Sc.,° Giuseppe Liotta, MD, § Maria Cristina Marazzi, XX, # Maria Grazia Mancini, B. Sc.,* Maria Cusato, Pharm D., ° Paola

Germano, XX, ^ Sandra Loureiro, MD, & Susanna Ceffa, B. Sc., @, Mario Regazzi, Pharm D., ° Stefano

Vella, MD,* Leonardo Palombi, MD,§

In press

0

10

20

30

40

50

60

70

80

%

plasma breast milk plasma breast milk

T0 (delivery) T7 (7 days postpartum)

Risk of having a detectable viral load in milk in Non-HAART Group

Delivery: OR = 4.8, [CI] : 1.7-13.6 1° Week:OR = 11.7, [CI] = 3.9-34.1

Non-HAART Group B

HAART Group A

1,7

2,7

3,7

4,7

me

dia

n H

IV R

NA

log

/ml

plasma whole milk milk lipid layer skim milk

T0 (delivery)

1,7

2,7

3,7

4,7

me

dia

n H

IV R

NA

log

/ml

plasma whole milk milk lipid layer skim milk

T7 (7 days postpartum)

Viral load in breast milk: comparison of HAART (A) and non-HAART (B) Groups at delivery and after 1 week

Non-HAART Group B

HAART Group A

Breastfeeding vs FormulaBreastfeeding vs Formula

Evaluation at first monthEvaluation at first month

HIV+HIV+

N.(%)N.(%)

HIV-HIV-

N.(%)N.(%)

TotalTotal

BreastfeedingBreastfeeding 2 (0.6)2 (0.6) 339 (99.6)339 (99.6) 341341

FormulaFormula 7 (0.9)7 (0.9) 802(99.1)802(99.1) 809809

A new approach – Month 1

Breastfeeding vs FormulaBreastfeeding vs Formula

Evaluation at sixth monthEvaluation at sixth month

HIV+HIV+

N.(%)N.(%)

HIV-HIV-

N.(%)N.(%)

BreastfeedingBreastfeeding 0(/)0(/) 78(100)78(100) 7878

FormulaFormula 15(1,8)15(1,8) 794 (98,2)794 (98,2) 809809

A new approach – Month 6

HIV status by parity at 1 HIV status by parity at 1 monthmonth

ParityParity

TotalTotal P1P1 P2P2 P3 P3

HIV+HIV+ 22 00 00

22

HIV-HIV- 286286 5050 33

339339

TotalTotal

288288 5050 33

341341

Malnourished and anemic children in the Malnourished and anemic children in the breastfed cohortbreastfed cohort

0

1020

3040

5060

7080

90100

YES NO

MalnourishedAnemic

NVP Toxicity in the DREAM CohortNVP Toxicity in the DREAM Cohort

NN IncidenceIncidence

Hepatic Hepatic reaction reaction

38/606*38/606* 6,3%6,3%

SJSSJS 8/7788/778 1.1%1.1%

Skin RushesSkin Rushes 17/77817/778 2.2%2.2%

NVP Toxicity in the DREAM CohortNVP Toxicity in the DREAM Cohort

* Women with at least 2 ALT/AST results available

ResistancesResistances

42 unselected women that completed the protocol were assessed for genotypic resistance, in a time period of between 2-6 months after therapy was interrupted:

All carried a subtype C strain (more prone to resistance to Nevirapine compared to subtype A and B)

37 (88.1%) showed no mutations associated with resistance

5 (11.9%) carried mutations associated with resistance to Nevirapine

3 : K103N

2 : G190S

Resistance to 3TC and AZT-D4T was not detectableCROI, Boston 2005

Distribution by HAART lineDistribution by HAART line

First line: First line: 4,855 (87,08%)4,855 (87,08%) First line Tox.mod:First line Tox.mod: 316 (5,66%) 316 (5,66%) Second line:Second line: 405 (7,26%) 405 (7,26%)

92,74% of patients are still in first line 92,74% of patients are still in first line with a median time of more than 2 with a median time of more than 2 yearsyears

DREAM costsDREAM costs

Total program: 4,350,000 USD

Cost per patient per year: 540 USD

DREAM costsDREAM costsHAART Population last update 2006HAART Population last update 2006

Cost distributionCost distribution::

ItemsItems TotTotPer Per paxpax Perc.Perc.

ARV TreatmentARV Treatment$1,999,6$1,999,6

8080 250250 46%46%

ARV Treatment 1° lineARV Treatment 1° line$1,540,7$1,540,7

2525 $204.5$204.5

ARV Treatment 2° lineARV Treatment 2° line $458,955$458,955 $987$987

ReagentsReagents $684,800$684,800 $86$86 16%16%

PersonnelPersonnel $662,200$662,200 $83$83 15%15%

FoodFood $400,000$400,000 $50$50 9%9%

Fixed costsFixed costs $245,000$245,000 $31$31 6%6%

Expatriate personnelExpatriate personnel $120,000$120,000 $15$15 3%3%

Training of personnelTraining of personnel $80,000$80,000 $10$10 2%2%

Administrative and logistical costsAdministrative and logistical costs $75,000$75,000 $9$9 2%2%

Testing ActivitiesTesting Activities $48,000$48,000 $6$6 1%1%

$4,314,6$4,314,6

8080 $539$539

Cost-effectiveness of PMTCT Cost-effectiveness of PMTCT programprogram

Premise:Premise:

Data gathered at the DREAM centre for PMTCT of Matola in MozambiqueDuration of program: 3 yearsWomen tested: 6175HIV-positive women: 1862 (30%)Women who joined the program: 1594Protocol followed: HAART from 25° week to six months after deliveryAll costs are considered, including ARV treatment just for the period from initiation of therapy to six months after deliveryUNAIDS indications for cost-effective analysis were followed

Results:Results:Total cost of 3 year programTotal cost of 3 year program $333,774,48$333,774,48

Reduction of riskReduction of risk 71.89%71.89%

Cost per infection avertedCost per infection averted $486,19$486,19

Cost per DALY savedCost per DALY saved $17,83$17,83

Public sector perspectivePublic sector perspective

Total cost of 3 year programTotal cost of 3 year program $58,593,46$58,593,46




Results:Results:Total cost of 3 year programTotal cost of 3 year program $333,774,48$333,774,48

Reduction of riskReduction of risk 71.89%71.89%



Public sector perspectivePublic sector perspective

Total cost of 3 year programTotal cost of 3 year program $58,593,46$58,593,46




Variables considered in the model

Sensitivity analysis


Independent variables inserted in the Independent variables inserted in the modelmodel

Life expectancy without AIDS in MozambiqueLife expectancy without AIDS in Mozambique 52.652.6

Discount rate on future benefits (DALY saved)Discount rate on future benefits (DALY saved) 3%3%

Discount rate on future costsDiscount rate on future costs 3%3%

Postnatal transmission rate of HIV without Postnatal transmission rate of HIV without interventionintervention 0.3590.359

DREAM transmission rate at one monthDREAM transmission rate at one month 0.0380.038

Discount on costs due to further benefits of VCT*Discount on costs due to further benefits of VCT* 30%30%

* VCT has benefits that go beyond the birth of children without HIV. Consequently costs sustained that do not influence the results being assessed should be deducted from program costs in the calculation of indicators examined.

Sensitivity analysis:Sensitivity analysis:


BaseBaseRate discount Rate discount DALY 0%-6%DALY 0%-6%

Rate discount Rate discount costs 0%-6%costs 0%-6%

Rate discount VCT Rate discount VCT 15%-45%15%-45%

Cost per infection Cost per infection avertedaverted $486,19$486,19 $486,19$486,19 $486,19$486,19 $500,63$500,63 $472,83$472,83 $590,38$590,38

$382,0$382,011

Cost per DALYCost per DALY $17,83$17,83 $9,72$9,72 $28,22$28,22 $18,36$18,36 $17,34$17,34 $21,65$21,65 $14,01$14,01

Savings sick Savings sick children public children public sectorsector

Cost per infection Cost per infection avertedaverted $123,51$123,51 $123,51$123,51 $123,51$123,51 $138,14$138,14 $109,98$109,98 $229,05$229,05 $17,98$17,98

Cost per DALYCost per DALY $4,53$4,53 $2,47$2,47 $7,17$7,17 $5,07$5,07 $4,03$4,03 $8,40$8,40 $0,66$0,66

HAART in pregnancy...HAART in pregnancy...

Is effective and the results are Is effective and the results are independent from the setting of independent from the setting of deliverydelivery

Makes possible the breastfeadingMakes possible the breastfeading Present a very limited life-Present a very limited life-

threatening risk and the hepatic threatening risk and the hepatic toxicity seems, in a large cohort, to toxicity seems, in a large cohort, to be limitedbe limited

HAART in pregnancy...HAART in pregnancy... Is well accepted by the patients: Is well accepted by the patients:

80% of the invited women 80% of the invited women completed the protocolcompleted the protocol

Is associated with a decreased rate Is associated with a decreased rate of viral resistance compared with of viral resistance compared with single dose nevirapinesingle dose nevirapine

Is cost-effectiveIs cost-effective

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TAP Program Mozambique DREAM, Treatment Acceleration Program Learning from the experiences gained and the challenges ahead November 30, 2006 TAP Program