1. Using HIV Surveillance Data to Evaluate
Outcomes of Site Randomized
Interventions in the TLC-Plus Study
Deborah Donnell*, Irene Hall, Y Jia, Angelique Griffin, Kathleen
Brady, Becky Grigg, Aaron Sayegh, Lucia Torian, Wafaa El Sadr
*Vaccine and Infectious Disease Division, Fred Hutchinson
Cancer Research Center, Seattle, WA
2011 National HIV Surveillance Conference: Atlanta, GA

2. The TLC-Plus Trial (HPTN 065)
• Feasibility study of implementing “Test and
Treat” for HIV Prevention in the US
• Five study components with feasibility
outcomes
• Two study components testing financial
incentives(FI) vs. Standard of care (SOC)
– Site randomized outcomes in two intervention
cities (Bronx NY, Washington DC)
(Session E07, Wednesday 8 am)

3. HPTN 065: Study Design
Expanded HIV Testing Linkage-to-Care:
• Social mobilization
Test Randomization of HIV Test Sites
• Universal offer of testing in ED/hospital
admission
FI to link to SOC to link to
care care
Linkage to Care
Prevention for Positives: Individual
randomization of HIV+
CARE plus SOC SOC alone
Provider & Patient Surveys Initiate Art per
current
• Knowledge and attitudes regarding ART
and FIs guidelines
Viral Suppression:
Randomization of HIV Care Sites
Viral
FI for viral SOC for viral
suppression suppression suppression

4. HPTN 065: Study Design
Expanded HIV Testing Linkage-to-Care:
• Social mobilization
Test
Randomization of HIV Test Sites
• Universal offer of testing in ED/hospital
admission
FI to link to SOC to link to
care care
Linkage to Care
Prevention for Positives: Individual
randomization of HIV+
CARE plus SOC SOC alone
Provider & Patient Surveys Initiate Art per
current
• Knowledge and attitudes regarding ART
and FIs guidelines
Viral Suppression:
Randomization of HIV Care Sites
Viral
FI for viral SOC for viral
suppression suppression suppression

5. Two site randomized components testing
efficacy of financial incentives
Linkage to Care Viral load suppression
• 20 testing sites in Bronx, NY and • 20 care sites in Bronx, NY and
Washington DC (40 total) Washington DC (40 total)
• 10 sites randomly selected to use • 10 sites randomly selected to use
FI coupons FI for achieving low VL
• Data from HIV Surveillance for • Data from HIV Surveillance for
linkage of newly tested HIV cases viral load of PHWH
– Number of newly tested cases in – Number of PLWH in care
the previous year – Among HIV-infected people in
– Among newly tested cases, care, proportion with last viral
proportion linked to care in 3 load < 400 copies/mL
months – Cannot assess whether on
antiretroviral therapy

6. HIV Surveillance used to assess site
aggregate data
• Baseline data
– Site selection
– Inform randomization (to achieve balance between arms)
– Conduct power calculations for site-randomized trial
• Follow-up data
– Study outcomes
– Monitoring of unintended effects (e.g. site migration)

7. HIV Surveillance Information Flow
TLC-Plus
People with HIV
CDC
Sources of Reports Local and/or State
Health Department
Hospital Practitioners
74,353
Private Practitioners
Public Clinics
Laboratories
Active
Case Finding
HPTN Statistical Center
Aggregate surveillance data
Also receives:
Aggregate testing data
Aggregate behavioral data

8. To assess site aggregate outcomes
HIV case identified as
accessing care within
jurisdiction
People with HIV
Testing/Care site
identified in
laboratory requisition
CDC
Sources of Reports Local and/or State
Health Department
Hospital Practitioners
74,353
Private Practitioners
Public Clinics
Laboratories
Active
Case Finding
Depends on
mandatory name Linkage of lab HPTN Statistical Center
based reporting of result to case Aggregate surveillance data
viral load and CD4
laboratory data Also receives:
Aggregate testing data
Aggregate behavioral data

9. Use of surveillance data for site
aggregate measures
• HIV Prevention Trials Network (HPTN) study
conducted using HIV surveillance data to measure
outcomes
• Only aggregate site data are released from DoH and
CDC as HPTN 065 data
– Study conducted under a waiver of informed consent
– Strict confidentiality laws for surveillance data

10. Issues in compiling aggregate data
• Health systems with multiple sites
– Not able to separate data unless lab requisitions can be
identified by location or provider
– Varied completeness of required information
• Completeness and consistency of lab data reporting
– Mandatory in New York City since 2005
• Mature QC systems between laboratories, state and city
– Electronic reporting in Washington DC began 2008
• QC process under development
• Data exchange with surrounding states under development
• Not all laboratory data reported electronically

11. Results: Site selection
• Site identification began in 2008, randomization
occurred in 2010/11
– Linkage to care – newly diagnosed cases
• Bronx NY: 2007 data for selection, 2008 for randomization
• Washington DC: 2008 data for selection, 2009 for
randomization
– Viral load suppression – most recent viral load at site
• Bronx: 2008 data for selection and randomization
• Washington DC: 2008 data for selection, 2009 for
randomization

12. HPTN 065: Test Site Selection
Bronx NY Washington D.C.
Total number of test sites Total number of test sites
identified by DOH: 27 identified by DOH: 31
Number of sites approached: Number of sites approached:
27 28
2 Not seeing HIV-infected
3 Did not respond
3 Declined
3 Did not respond
Number of sites that signed Number of sites that signed
LoI: 19 LoI: 25
1 Combined 2 Combined
4 Test volume too low
Number of sites selected for Number of sites selected for
study participation: 18 study participation: 19
Randomized Randomized Randomized Randomized
to FI: 9 to SOC: 9 to FI: 10 to SOC: 9

13. HPTN 065: Care Site Selection
Bronx NY Washington D.C.
Total number of care sites Total number of care sites
identified by DOH: 36 identified by DOH: 32
Number of sites approached: Number of sites approached:
36 27
2 Not seeing HIV-infected
1 Declined
3 Declined
3 Did not respond
4 Did not respond
2 Other reason
Number of sites that signed Number of sites that signed
LoI: 25 LoI: 23
2 Combined 3 Combined
3 Low volume of patients 1 Declined
Number of sites selected for Number of sites selected for
study participation: 20 study participation: 19
Randomized Randomized Randomized Randomized
to FI: 10 to SOC: 10 to FI: 10 to SOC: 9

14. Calculating power for a site randomized study
Linkage to Care Viral suppression
(Outcome: Newly tested linked (Outcome: VL <400 copies/mL)
w/i 3 months)
• Total number of sites • Total number of sites
• Mean number of HIV • Mean number of cases in
positive cases per site care per site
• Baseline probability of • Baseline proportion of viral
linkage to care suppression
• Intracluster correlation • Intracluster correlation
coefficient for linkage coefficient for low viral load
Variability in Variability in VL <
linkage probability 400 copies/mL
across sites across sites

15. Study design: Linkage to Care
Bronx Bronx Washington Washington
(2007) (2008) DC (2008) DC (2009)
Number newly diagnosed cases
Median 13 13 24 20
(Q1, Q3) (9-41) (3-44) (13-60) (3-44)
Mean 22 28 40 38
Proportion linked to care in 3 months
Median 75% 69% 77% 54%
(Q1, Q3) (49%-86%) (50%-86%) (57%-87%) (33%-71%)
ICC* 0.27 0.42 0.31 0.64
*Intracluster correlation coefficient

16. Study design: Viral load < 400 copies/mL
Bronx Bronx Washington Washington
(2008) (2008) DC (2008) DC (2009)
Number of cases assessed at care site
Median 174 251 100 153
(Q1, Q3) (121-310) (130-806) (48-229) (50-348)
Mean 692 625 245 311
Proportion with HIV viral load suppression
Median 57% 57% 37% 64%
(Q1, Q3) (39%-60%) (54%-61%) (27%-50%) (56%-72%)
ICC* 0.07 0.04 0.11 0.18
*Intracluster correlation coefficient

17. Power of site randomized studies
Linkage to Care Viral suppression
• 40 sites (37 sites) • 40 sites (39 sites)
• 54 linkage cases per • 180 cases in care per
site (mean 33 per year) site (mean 481 per site)
• ICC of 0.27 • ICC of 0.11
• 80% power to detect • 80% power to detect
increase from 67% to increase from 60% to
80% linkage to care 66% VL <400 copies/mL

18. Randomization Strategy
• Restricted randomization
– Small number of sites
– Protect against imbalance in factors predicting
outcome
– Volume of site; baseline outcome measure
• Randomization index:
– Sites divided into R1, R2
t statistic for t statistic for
difference in difference in
site volume baseline outcomes

19. Data for randomization
Baseline linkage to care Viral load suppression
160 6000
140
5000
Number of new diagnoses
120
Number of patients
4000
100
80 3000
60
2000
40
1000
20
0
0
0% 20% 40% 60% 80% 100%
0% 20% 40% 60% 80% 100% 120%
Proportion linked to care in 3 mos. Proportion with VL < 400 cp/mL

20. Issues in conducting randomization
• Test sites could not start until care sites had initiated
study
• Additional restriction added to ensure balance for
highest volume sites
• Randomization of sites after IRB approvals required
different start times – added blocks
– Washington DC
• Test: two blocks (Feb and March 2011)
• Care: three blocks (October 2010, Jan and March 2011)
– Bronx
• Test: one block (Feb 2011)
• Care: one block (Jan 2011)

21. Summary
• HIV surveillance data were aggregated in selected
sites to inform study design and randomization for
HPTN 065 (TLC-Plus)
• Linkage to care at baseline
– Levels of linkage to care were similar in Bronx, NY and
Washington DC.
– More cases were being identified in Washington DC.
• Suppressed VL at baseline
– Levels of viral suppression were modest and similar in
Bronx and Washington DC
– Includes patients not on ART.
– More PLWH were in care in the Bronx

22. Implications
• HIV surveillance data has the potential to provide
information for assessment of site level outcomes –
an opportunity for conducting rigorous
implementation science
• Additional resources provided at DoH to facilitate
obtaining timely information – especially needed for
site identification
• Upload of complete lab data (CD4 and viral load) into
eHARs facilitates uniform assessment of outcomes
across jurisdictions

23. Acknowledgments
• Special thanks to HIV surveillance staff in New York City, Washington DC.
• HPTN 065 is sponsored by the NIAID and NIMH under Cooperative
Agreement #UM1 AI068619 and #UM1 AI068617, by the CDC, National
Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, via an
interagency agreement.
• The findings and conclusions in this report are those of the authors and do
not necessarily represent the official position of the Centers for Disease
Control and Prevention.