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Design Issues and Implications for a Domestic Research Agenda Sten Vermund, Wafaa El-Sadr, Kenneth Mayer on behalf of the HPTN. HPTN Test and Treat (TNT). Outline of Presentation. Conceptual framework for TNT Unique features of US HIV epidemic US testing initiatives

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Hptn test and treat tnt

Design Issues and Implications for a Domestic Research Agenda

Sten Vermund, Wafaa El-Sadr, Kenneth Mayer

on behalf of the HPTN

HPTN Test and Treat (TNT)


Outline of presentation

Outline of Presentation

  • Conceptual framework for TNT

  • Unique features of US HIV epidemic

  • US testing initiatives

    • The Bronx Knows Initiative

    • Washington DC Initiative

    • Layering research on public health programs

  • Experimental Designs: Current Studies

    • BROTHERS and ISIS

    • Interventions in BROTHERS-II and ISIS-Plus

  • Key Research Questions

    • Study Designs and study outcomes

    • Next Steps  your questions and views


Hptn test and treat tnt

Model assumes…

Generalized epidemic

High prevalence & incidence

High population coverage with repeated testing and universal treatment

Earlier treatment than current SOC

Lancet 2009; 373:48-57


Test and treat hypothesis

Test and Treat Hypothesis

Test

Adoption of safer risk behaviors by HIV+ persons

Treat with ART

+

Adherence

Maintain viral suppression

+

Decrease in HIV Transmission


Conceptual framework and obstacles for a tnt strategy

In US = Localized into geographic and population hotspots

No definitive evidence yet of risk/benefits of early ART

For treatment: START; HPTN052/ACTG5245

For prevention: HPTN 052/ ACTG5245

Challenges in bridging to care and in long-term maintenance

ART adherence and HIV suppression

Conceptual Framework █ and obstacles █ for a TNT Strategy

Identify HIV (+) persons unaware of their HIV status

Risk reduction among persons testing HIV (+)

Bridge to care for ART

Eligibility from current guidelines, or

ART for all with HIV infection

Maintenance of high ART adherence rates for maximal RNA suppression

Decrease in HIV transmission from virally suppressed persons


Epidemiology of hiv aids in the us

Epidemiology of HIV/AIDS in the US

  • Disparities

    • in race/ethnicity

    • in geography

    • in sexual exposure


Estimated number of new hiv infections by transmission category 1977 2006

Estimated number of new HIV infections by transmission category, 1977-2006

*50 States and District of Columbia

MSM

IDU

HET


Estimated rates of new hiv infections by race ethnicity 2006

Estimated rates of new HIV Infections, by race/ethnicity, 2006*

Total Male: 34.3 per 100,000

Total female: 11.9 per 100,000

Courtesy of Kevin Fenton, CDC

*50 States and District of Columbia


Hptn test and treat tnt

White, not Hispanic

Black, not Hispanic

Hispanic

Asian/Pacific Islander

American Indian/Alaska Native

Estimated AIDS Cases among Adult and Adolescent MSM, by Region and Race/Ethnicity, 2006—50 States and DC

3,500

3,000

2,500

2,000

No. of cases

1,500

1,000

500

0

West

Northeast

Midwest

South

n=3,765

n=3,220

n=2,150

n=6,939

Note. The data have been adjusted for reporting delay and cases without risk factor information were proportionally redistributed.


Hptn test and treat tnt

Estimated HIV/AIDS Cases among MSM, Aged 13–24 years, by Race/Ethnicity, 2001–2006—33 States

2,000

1,600

1,200

Black, not Hispanic

No. of cases

800

White, not Hispanic

Hispanic

400

Asian/Pacific Islander

American Indian/Alaska Native

0

2001

2002

2003

2004

2005

2006

Year of diagnosis

Note. The data have been adjusted for reporting delay and cases without risk factor information were proportionally redistributed.


Hptn test and treat tnt

HIV Prevalence Among 1,767 MSM, by Age Group and Race/Ethnicity—Baltimore, LA, Miami, NYC, San Francisco

Age Group (yrs)

18-24410 57(14)45(79)

25-29303 53(17)37(70)

30-39585171(29)83(49)

40-49367137(37)41(30)

≥ 50102 32(31)11(34)

Unrecognized HIV Infection

No. %

HIV

Prevalence

No. %

Total

Tested

Race/Ethnicity

White616127(21)23(18)

Black444206(46)139(67)

Hispanic466 80(17)38(48)

Multiracial 86 16(19) 8(50)

Other139 18(13) 9(50)

Total1,767450(25)217(48)

MMWR June 24, 2005


Us national health interview survey nhis

US National Health Interview Survey (NHIS)

Annual, cross-sectional U.S. household probability sample conducted by NCHS/CDC (excludes institutionalized individuals)

Provides estimates for a broad range of health measures for the U.S. population, including HIV testing

Testing Efforts in the US


Hiv testing in nhis 2006

HIV Testing in NHIS: 2006

U.S. adults estimated to have been tested for HIV

40% (71.5 million) at least once

10.4% (17.8 million) in the preceding 12 months

REF: Duran et al, MMWR, Aug. 2008


Persons are being tested in clinical settings

Persons are being tested in clinical settings

- 2006 National Health Interview Survey


National testing initiative 2007

National Testing Initiative 2007

Goal: To increase HIV testing opportunities for populations disproportionately affected by HIV

Focus on Black Americans unaware of their status

Funding: $35 million awarded Sept. 2007 to 23 jurisdictions with the highest number of AIDS cases among Black Americans

Increased to 25 jurisdiction in 2008


Hiv testing in nyc

HIV Testing in NYC


Hiv testing in nyc1

HIV Testing in NYC

FY ’07FY ’08

City-Sponsored Tests: 143,719209,194

(Internal & External Programs)

% Rapid Tests 98.0%98.7%

Positive Tests 1,660 2,868

% Seropositive 1.2% 1.4%

From: Blayne Cutler, MD PhD, NYC Dept of Health & Mental Hygiene

NYC DOHMH BHIV Testing Unit, data reported as of 12/31/08


Nyc internal testing programs

NYC Internal Testing Programs

Routinely offered:

STD clinics

TB clinics

NYC jails

Field Services Unit

Field testing of partners of the newly diagnosed began Feb. 2008

From: Blayne Cutler, MD PhD, NYC Dept of Health & Mental Hygiene


Hptn test and treat tnt

21 Hospitals/Clinics/CBOs via DOHMH

37 Hospitals/Clinics/CBOs via RW funds

21 CBOs funded by NY City Council

limited testing: only 4,453 tests in FY’08

6 CBOs: social network-based testing

NYC External Testing Programs

From: Blayne Cutler, MD PhD, NYC Dept of Health & Mental Hygiene


Hptn test and treat tnt

“The Bronx Knows” Initiative

  • Test every Bronx resident who has never been tested (focus on 18-64 y.o)

  • Identify all undiagnosed HIV-positive persons in the Bronx

  • Link all persons who test HIV+ to high quality care and supportive services


Hptn test and treat tnt

Why the Bronx?

Epidemiology In 2006-

Almost 25% of all NYC diagnoses in Bronx residents

Over 25% of Bronx residents concurrently diagnosed with HIV and with AIDS

Nearly 1/3 of AIDS-related deaths in Bronx residents


Hptn test and treat tnt

How many need to be tested?

Est. Population of the Bronx, 2006: 1.36 M.

Bronx Population, age 18–64 years: 821,000

PLWHA, ages 18–64 yrs: 20,218

No. Adults Eligible for HIV Testing: 800,750

30.7% Never Tested for HIV, Bronx

No. Adults To Be Tested for HIV, Bronx: 245,830

Minimum Estimate


Hiv testing in washington dc

HIV Testing in Washington, DC

From: Shannon Hader, MD, Washington DC Dept of Health

  • 15,120 persons reported living with HIV/AIDS in the District as of 12/31/07

  • 7,432 new HIV/AIDS cases reported between 2003-2007

  • One-third to one-half of people (locally) may be unaware of their HIV status (Source: NHBS data)

Population Prevalence

0.0 - 0.6

0.7 - 1.2

1.3 - 1.8

1.9 - 2.4

2.5 - 3.0

2009

PREVIEW


Dc hiv aids prevalence rates by race ethnicity and sex 2007

DC HIV/AIDS Prevalence Rates by Race/Ethnicity and Sex, 2007

6.5

%

1.0

%

3.0

Overall DC Prevalence

White

Females

0.2%

Hispanic

Females

0.7%

Black

Females

2.6%

White

Males

2.6%

Hispanic

Males

3.0%

Black

Males

6.5%

24

2009

PREVIEW

Proportion of DC Residents Diagnosed and Living with HIV/AIDS


Hiv rapid testing expansion in dc

HIV Rapid Testing Expansion in DC

N=43,271

N=72,864

68.4% increase in number of tests done

97% of new HIV positives were identified in clinical settings

94% of new HIV positives were identified in clinical settings

2009

PREVIEW

25


Time from hiv diagnosis to care entry

Time from HIV Diagnosis to Care Entry*

1,340

1,827

1,635

1,502

1,342

1,510

50%

2009

PREVIEW

26


Key research questions in this field

Key Research Questions in this Field

  • Does an HIV+ person who is treated aggressively transmit less to an HIV(-) sexual partner? HPTN 052

  • Does expanded HIV testing reduce HIV transmission in a given community? HPTN 043

  • Can we engage hard-to-reach populations? HPTN 061 (BROTHERS) and HPTN 064 (ISIS)

  • Should HIV therapy be started earlier than currently recommended? HPTN 052/ACTG 5245 & INSIGHT START

  • Can a combination of expanded testing and bridging to good HIV/AIDS care reduce HIV incidence? “TNT”


What might we test in tnt

What might we test in TNT?

  • Any or all of these to make an impact on community-level HIV incidence:

    • Expanded testing and bridging to care

      • Peer navigators

    • Improved adherence counseling and mnemonics within care

      • Treatment “buddies”

    • Positive prevention messages for persons in care

    • Social marketing of prevention messages


In whom would we measure outcome

In whom would we measure outcome?

  • Seroincidence from sentinel sites

    • STD clinics? People come for symptoms

    • ANC? People come to have babies

    • Discard syphilis tests? Mix of routine tests and assessment of risks or symptoms

  • Seroincidence from population-based samples

    • General? MSM? IDU? High risk women?

    • National surveys like NHBS as complements to targeted testing


How would we measure outcome

How would we measure outcome?

  • BED-CEIA to screen

    • Avidity in BED (+)

      • Modeling to adjust for ART, VL, CD4

  • Acute infection surveillance

  • Modeling from changes in seroprevalence among new IDUs and/or adolescents

  • Complemented by behavioral surveillance, process/output measures


Current hptn studies

Current HPTN Studies

Experimental Designs

Potential Future Studies


Current hptn efforts feasibility studies hptn061 and 064

Current HPTN EffortsFeasibility Studies: HPTN061 and 064

BROTHERS: Community-Based, Multi-component

HIV Prevention Intervention for Black MSM

ISISHIV Seroincidence Study in Women


Hptn feasibility studies

HPTN Feasibility Studies

Brothers

ISIS

Accurate estimation of HIV incidence in US women at risk for HIV

Feasibility of follow-up of cohort of at risk women

Feasibility of HIV as the primary outcome for prevention study in US women

  • Feasibility of recruitment of Black MSM

  • Feasibility of recruitment of their sexual/social networks

  • Feasibility of HIV testing of index cases and network members

  • Feasibility of peer navigation for prevention and care


Research design options

Research Design Options

Community-level RCT

Stepped wedge

Factorial

Quasi-experiment

Pseudo-randomized

Before-After

Note: Process indicators would accompany any design


Proposed design of brothers ii

Proposed Design of BROTHERS-II

Community-level randomization

(12 to 30 cities for full RCT)

Intervention cities

Intervention delivered over 1-2 years

Control cities

Venue-based time-space sampling of Black MSM

  • Package of Interventions

  • Testing

  • Referral and Linkage

  • Suppression of viral load

HIV incidence estimates


Hptn test and treat tnt

ISIS-Plus: Two Level Factorial Design

WI = women’s intervention group, WC = women’s control group

CI = Community Intervention group, CC = Community control group,


Quasi experimental design

Quasi-experimental design


Process output variables will be measured regardless of design

Process/Output Variables will be measured regardless of design


Modeling

Modeling

Build models based on US HIV epidemic

Assess effectiveness of various interventions over time

Identify interventions most likely to be effective based on various assumptions

Model cost effectiveness

Variables would include: all program costs, population

proportion tested, treated, suppressed, breaking through, living longer, behaviors as changing over time


Next steps

Next Steps

  • Establish partnership with CDC, NYC DOH, DC DOH, and others to:

    • Determine methods to utilize routinely collected data to determine effect of HIV testing and other public health initiatives

    • Assess various programmatic components

  • Continue efforts to determine feasibility of enrollment of prevention cohorts in the US

  • Design definitive TNT trial, preparing for anticipated USG investments

  • Utilize modeling to assist in choice of interventions and anticipate their effect


Your critical comments are most welcome

Your CRITICAL comments are most welcome!!

  • Wafaa, Ken, and Sten acknowledge…

    • Protocol chairs and investigators

      • ISIS and BROTHERS

      • HPTN 043 and 052

    • Tom Coates, Jessica Justman, Bernie Branson, Shannon Hader, Blayne Cutler,


Extra slides

Extra Slides


Routinely collected data dohmh funded testing programs

Routinely Collected Data(DOHMH-Funded Testing Programs)

Routinely-collected data for all persons tested (+/-)

Tests conducted and tests results

Whether previously tested for HIV

Self-reported HIV status prior to testing

Demographics of persons tested

Age and Sex (including transgender)

Race, Ethnicity, Zip code

Additional Data for HIV(+) Persons

Risk Factors

CD4+ cells and VL

All results for each individual

Concurrent AIDS diagnosis, if any

STAHRS-based seroincidence estimates from WBs

Available Aggregate Data

Index of “community VL”

Median, mean, range CD4+ cells

% linked to care within 3 months

% with concurrent AIDS diagnosis

% of new diagnoses that are recent infections


Community level rcts

Community-level RCTs


Stepped wedge community level rcts

Stepped-wedge Community-level RCTs


Two level factorial community rct study design one example

Two Level Factorial Community RCT Study Design: One example


Factorial community level rct

Factorial Community-level RCT


Hptn test and treat tnt

Epidemiology of HIV in US: Ethnic and racial disparities


Hptn test and treat tnt

Epidemiology of HIV in US:Geographic Disparities


New aids cases and late testers

New AIDS Cases and “Late Testers”

Persons newly diagnosed with AIDS, and

proportion first diagnosed with HIV within 12 months, 2001-2006 (N=4,640)

992

842

780

668

692

54.0%

666

30.3%

646

32.3%

37.1%

43.3%

37.8%

33.9%

69.7%

67.7%

46.0%

62.9%

62.2%

56.7%

66.1%

51

51

2009

PREVIEW


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