aidsrelief: optimizing the durability of first line treatment

UMSOM-IHVDivision of Clinical Care & Research

International Programs1

AIDSRelief: Optimizing the Durability of First line Treatment

Robb Sheneberger, MDMartine Etienne-Mesubi, PhDMian B. Hossain, PhDRobert R. Redfield, MD

University of Maryland School of MedicineInstitute of Human Virology

July 25, 2012

The AIDSRelief Consortium

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AIDSReliefOver the eight years of the program

Supported 276 mostly rural treatment facilities in ten countries

Delivered HIV care and treatment to 706,593 clients Initiated 395,088 patients on ART, including 268,631

currently on treatment at transition quarter

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Durability of the Initial Regimen is the Key to Sustainability, Scalability and Long Term ARV Access to Global HIV Treatment Programs

Durability of Initial Regimen: Key Factors

Regimen Choice

Treatment Strategy

Care Delivery System

Durability of the Initial Regimen Systematic implementation of:

Regimen Choice Treatment Strategy Care Delivery Systems

Lack of durability shifts resources from these key areas reducing the ability to progressively improve outcomes

Continued improvement of treatment outcomes to the initial regimen remains a critical area

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We used national guidelines but moved to greater durability as we were able to work with National governments to transition to more effective NRTIs

(i.e. TDF based regimens)

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What we learned about: Regimen Choice

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0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

0 3 6 9 12 15 18 21 24 27 30 33 36Months

D4T/3TC/NVP D4T/3TC/EFV AZT/3TC/NVPAZT/3TC/EFV TRUVADA/NVP TRUVADA/EFV

PLO AIDSRelief: 2008Time to Switch to 2nd line Regimen

D4T/3TC/EFV

Truvada/NVP or EFV

N= 5199

What we learned about:Regimen Choice

With increased use of TDF based regimens an in-depth review showed:

On treatment analysis TDF/XTC/EFV had significantly higher odds of viral suppression than AZT/3TC/NVP (p<0.03) or TDF/XTC/NVP (p<0.01)

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XTC=3TC or FTC

Amoroso, A, et al Treatment Outcomes of Recommended First-Line Antiretroviral Regimens in Resource-Limited Clinics JAIDS 1 July 2012 - Volume 60 - Issue 3 - p 314–320

N= 3862

What we learned about:Regimen Choice

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Missed Appointments and Initial Regimen

Fewer people missed appointments on TDF compared to the other regimensN=7,513 p<0.004

What we learned about:Treatment Strategy

We used national guidelines but moved to greater durability as we were able to work with National governments to treat earlier

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Baseline CD4 and viral suppression rates

Higher the initial CD4, greater the chances of increasing durability

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What we learned about:Treatment Strategy

p<0.001

N=7,513

What we learned about:Treatment Strategy

WHO Stage at ART Initiation of Active Patients

WHO Stage at ART initiation of Care-ended Patients

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N=1,762N=9,747

Mean Baseline CD4 over time, by cohort

140

50

100

150

200

250

300

350

400

450

Ken2006 Zam2006 Uga2006 Ken2007 Nig2007 Zam2007 Ken2008 Nig2008 Tan2008 Uga2008 Zam2008 Nig2009 Rwa2011 Nig2011

N=13,135

mean baseline CD4 c/mm3= 229

On Treatment Viral Suppression in Randomly Selected Patients 2006-2011

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93.1

80

88.1

94.9

86.7

91.2 91.5

84 83.4

89 89.2 90.588.7

90.6

81.5

70

75

80

85

90

95

100

Avg=88.2

N=13,770

What we learned about: Care Delivery System

We had greater flexibility with the care delivery system and found that patients achieved greater durability in clinical settings that provided comprehensive treatment support, follow up and treatment education

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What we learned about: Care Delivery Structure

Year 1- initial start up Year 5- follow up

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n=27 sites; n= 13,391 persons

4.3% 4.1%

2.2%

0%1%2%3%4%5%6%7%8%9%

10%

Percent loss to

follow up

Tier I (

n=0)

Tier II

(n=20)

Tier III

(n=3

1)

Tier IV

(n=9

2)

n=143 sitesSites with fewer support systems had greater loss to follow up

Etienne, M et. al. Situational analysis of varying models of adherence support and loss to follow up rates; findings from 27 treatment facilities in eight resource limited countries; Trop Med Int Health. 2010 Jun;15 Suppl 1:76-81.

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With consistent and systematic implementation of: Regimen Choice

TDF favored over D4T or AZT EFV favored over NVP

Treatment Strategy - starting early = better outcomes Care Delivery Systems - community based support

Durable viral suppression in the most rural settings is possible

Final Lessons Learned

Final Lessons We Are Learning The care delivery structure is profoundly critical

Overall loss to follow up rates have been increasing as funding as been decreasing

Insufficient investment made to support health care delivery structures to sustain optimal outcomes

The number of deaths, loss to follow up, and dropped out of care may hit critical levels where many of our gains will be lost, and care and treatment will become more complex and costly

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Thank you!

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