using hiv surveillance data to evaluate outcomes of site randomized interventions in the tlc-plus...

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

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)

Test

Linkage to Care

Initiate Art per current

guidelines

Viral suppression

Viral Suppression: Randomization of HIV Care Sites

FI for viral suppression

SOC for viral suppression

Prevention for Positives: Individual randomization of HIV+

CARE plus SOC SOC alone

HPTN 065: Study Design Linkage-to-Care:

Randomization of HIV Test Sites

FI to link to care

SOC to link to care

Expanded HIV Testing • Social mobilization • Universal offer of testing in ED/hospital

admission

Provider & Patient Surveys

• Knowledge and attitudes regarding ART and FIs

Test

Linkage to Care

Initiate Art per current

guidelines

Viral suppression

Viral Suppression: Randomization of HIV Care Sites

FI for viral suppression

SOC for viral suppression

Prevention for Positives: Individual randomization of HIV+

CARE plus SOC SOC alone

HPTN 065: Study Design Linkage-to-Care:

Randomization of HIV Test Sites

FI to link to care

SOC to link to care

Expanded HIV Testing • Social mobilization • Universal offer of testing in ED/hospital

admission

Provider & Patient Surveys

• Knowledge and attitudes regarding ART and FIs

Two site randomized components testing efficacy of financial incentives

Linkage to Care • 20 testing sites in Bronx, NY and

Washington DC (40 total)

• 10 sites randomly selected to use FI coupons

• Data from HIV Surveillance for linkage of newly tested HIV cases – Number of newly tested cases in

the previous year

– Among newly tested cases, proportion linked to care in 3 months

Viral load suppression • 20 care sites in Bronx, NY and

Washington DC (40 total)

• 10 sites randomly selected to use FI for achieving low VL

• Data from HIV Surveillance for viral load of PHWH – Number of PLWH in care

– Among HIV-infected people in care, proportion with last viral load < 400 copies/mL

– Cannot assess whether on antiretroviral therapy

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)

HIV Surveillance Information Flow TLC-Plus

Sources of Reports

Hospital Practitioners Private Practitioners Public Clinics Laboratories

CDC

74,353

HPTN Statistical Center Aggregate surveillance data Also receives: Aggregate testing data Aggregate behavioral data

Active Case Finding

Local and/or State Health Department

People with HIV

To assess site aggregate outcomes

Sources of Reports

Hospital Practitioners Private Practitioners Public Clinics Laboratories

CDC

74,353

HPTN Statistical Center Aggregate surveillance data Also receives: Aggregate testing data Aggregate behavioral data

Active Case Finding

Local and/or State Health Department

People with HIV

Depends on mandatory name based reporting of viral load and CD4 laboratory data

HIV case identified as accessing care within

jurisdiction

Testing/Care site identified in laboratory requisition

Linkage of lab result to case

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

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

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

HPTN 065: Test Site Selection

1 Combined

3 Did not respond

Total number of test sites identified by DOH: 27

Number of sites approached: 27

Number of sites that signed LoI: 19

Number of sites selected for study participation: 18

Randomized to FI: 9

Randomized to SOC: 9

Total number of test sites identified by DOH: 31

Number of sites that signed LoI: 25

Number of sites selected for study participation: 19

Randomized to FI: 10

Randomized to SOC: 9

Number of sites approached: 28

2 Not seeing HIV-infected 3 Declined 3 Did not respond

2 Combined 4 Test volume too low

Bronx NY Washington D.C.

HPTN 065: Care Site Selection

2 Combined 3 Low volume of patients

1 Declined 3 Did not respond

Total number of care sites identified by DOH: 36

Number of sites approached: 36

Number of sites that signed LoI: 25

Number of sites selected for study participation: 20

Randomized to FI: 10

Randomized to SOC: 10

Total number of care sites identified by DOH: 32

Number of sites that signed LoI: 23

Number of sites selected for study participation: 19

Randomized to FI: 10

Randomized to SOC: 9

Number of sites approached: 27

2 Not seeing HIV-infected 3 Declined 4 Did not respond 2 Other reason

3 Combined 1 Declined

Bronx NY Washington D.C.

Calculating power for a site randomized study

Linkage to Care (Outcome: Newly tested linked

w/i 3 months)

• Total number of sites

• Mean number of HIV positive cases per site

• Baseline probability of linkage to care

• Intracluster correlation coefficient for linkage

Viral suppression (Outcome: VL <400 copies/mL)

• Total number of sites

• Mean number of cases in care per site

• Baseline proportion of viral suppression

• Intracluster correlation coefficient for low viral load

Variability in

linkage probability across sites

Variability in VL < 400 copies/mL

across sites

Study design: Linkage to Care

Bronx (2007)

Bronx (2008)

Washington DC (2008)

Washington 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

Study design: Viral load < 400 copies/mL

Bronx (2008)

Bronx (2008)

Washington DC (2008)

Washington 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

Power of site randomized studies

Linkage to Care

• 40 sites (37 sites)

• 54 linkage cases per site (mean 33 per year)

• ICC of 0.27

• 80% power to detect increase from 67% to 80% linkage to care

Viral suppression

• 40 sites (39 sites)

• 180 cases in care per site (mean 481 per site)

• ICC of 0.11

• 80% power to detect increase from 60% to 66% VL <400 copies/mL

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 difference in site volume

t statistic for difference in

baseline outcomes

Data for randomization

0

20

40

60

80

100

120

140

160

0% 20% 40% 60% 80% 100% 120%

Num

ber o

f new

dia

gnos

es

Proportion linked to care in 3 mos.

Baseline linkage to care

0

1000

2000

3000

4000

5000

6000

0% 20% 40% 60% 80% 100%

Num

ber o

f pat

ient

s

Proportion with VL < 400 cp/mL

Viral load suppression

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)

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

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

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.