Rapid Entry and ART Initiation in HIV Care: Implementation ... · N Engl J Med. 2015;373: 795-807; TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015; 373:808-22. Early ART led to

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Rapid Entry and ART Initiation in HIV Care: Implementation of a New Paradigm

Jonathan Colasanti, MD, MSPH

Assistant Professor of Medicine & Global Health, Emory University

Associate Medical Director, Infectious Disease Program, Grady Health System

Disclosures

• No Relevant Relationships

Objectives

Upon completion of the presentation, learners should be able to:

1. Describe the rationale and evidence for rapid entry into HIV Care

2. Compare models of rapid entry from around the globe

3. Identify challenges with implementation of rapid entry programs

2

Q1: In your clinics, on average, how long after patients enroll do they begin ART?

A. Same day

B. Within 2 weeks

C. Within 1 month

D. Greater than 1 month

Why Push for Earlier Antiretroviral Therapy?

• Shifting guidelines (DHHS & WHO)

• High attrition rates from positive test to ART initiation

• Delays in treatment associated with: – Increased mortality

– Diminished CD4 recovery

– Avoidable hospitalizations • Higher costs of treatment for opportunistic infections

– HIV transmission

• Improved drug tolerability and durability

• Lower risk for resistance with current regimens

Q2: Since what year have the DHHS Antiretroviral Guidelines recommended ART for all?

A. 2008

B. 2010

C. 2012

D. 2014

E. 2016

3

CD4+

Count,

cells/mm3

1998 2001 2006 2008 2009 2012

> 500 Offer if

VL > 20,000

Offer if VL

> 55,000

Consider if VL

≥ 100,000

Consider in certain groups

Consider Treat

350-500 Offer if

VL > 20,000

Consider if VL

> 55,000

Consider if VL

≥ 100,000

Consider in certain groups

Treat Treat

200-350 Offer if

VL > 20,000

Offer, but controversy

exists

Offer after discussion with patient

Treat Treat Treat

< 200 or symptomatic disease

Treat Treat Treat Treat Treat Treat

Department of Health and Human Services: Changing Criteria for Initiating ART

Adapted from Clinical Care Options.. Putting the DHHS HIV Treatment Guidelines Into Practice. January 2013.

The Big Three: 3 Studies Shifted the Guidelines

Final results in 2016 - Early ART 93% lower risk of transmission - Zero linked infections with VS index patient

Cohen et al. N Engl J Med 2016;375:830-9; Cohen et al. N Engl J Med 2011;365:493-505; INSIGHT START. N Engl J Med. 2015;373: 795-807; TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015; 373:808-22.

Early ART led to HR of 0.43 for death, AIDS related events or serious non-AIDS

related event

Earlier ART resulted in HR of 0.56 for death or severe HIV-related illness

Sax P. NEJM Journal Watch. May 27 2015.

4

The End of the AIDS Epidemic by 2030?

= 73% of PLWH VS

UNAIDS 2014

Case: Mr G

• 54 y.o. man with HTN, dx w/ HIV in 1997 and deferred

entry into care until 2002, as he was told CD4 was too

high to start meds

– 2002 - 2007: TDF/FTC/EFV (STR) VS

– 2007 - 2008: incarcerated in AL ART VS

– 2008: Auburn, AL on ART

• Picked up meds until Rx card ran out

• Out of care x 7 years

Case (cont.)

• Homeless, increasing use of alcohol, crack, marijuana,

oxycontin x 2 years.

• Visibly upset upon entering the clinic. Reports becoming

increasingly depressed since going off of ART.

• Wants to restart ART

NO DOCUMENTS

5

RAPID ART: THE EVIDENCE

South Africa, San Francisco, Haiti, Uganda

Rapid Initiation of Treatment (RapIT)

• Unblinded randomized controlled trial at two public sector HIV clinics in South Africa

• Single visit initiation of ART (HIV test or eligible CD4) • Inclusion: ≥ 18 yo, non-pregnant, ART eligible (CD4 ≤ 350) • Primary Outcome

– VS (≤ 400 c/mL) within 10 mo study enrollment

• Secondary Outcome – Initiation of ART by 90 days – Retention in care – Time to ART initiation – Feasibility and acceptability of intervention

Rosen S et al. PLoS Med 2016 .

Standard v RAPID Arm

Rosen S et al. PLoS Med 2016 13(5): e1002015.

6

RapIT: Baseline Characteristics

Table 1. Baseline characteristics of study sample (n = 463).

Rosen S et al. PLoS Med 2016.

Variable Standard Arm N = 229

Rapid Arm N = 234

Age 35.8 (29.5-41.6) 34.2 (29 – 40.1)

Sex (% Female) 132 (58%) 129 (55%)

CD4 (cells/mm3) (median, IQR) 195 (103-322) 224 (128-327)

Purpose of Clinic Visit

Have HIV Test (dx today) 100 (44%) 90 (38%)

Provide blood for CD4 8 (4%) 10 (4%)

Receive CD4 Result 109 (47%) 112 (48%)

Other 11 (5%) 22 (105)

Reason for Treatment eligibility

CD4 count < 350 182 (79%) 183 (78%)

Clinical Stage 3 or 4 3 (1%) 4 (2%)

Excluded (not eligible) 44 (20%) 47 (20%)

RapIT: Time to ART Initiation


17 days

0 days

The Hope for Better Long Term Outcomes


7

Q3: Same day ART may increase rates of VS, but patients are reluctant to start quickly

A. TRUE

B. FALSE

San Francisco General Hospital RAPID Model

RAPID visit: ART start • Disclosure, counseling • Registration • Insurance • Housing/SU/MH • Labs • Counseling • Medical eval

PCP Visits • VL monitoring • ART management • Adherence • Retention

HIV+ Diagnosis • Disclosure • Referral • Scheduling

1st Clinic Visit • Registered • Insured • Housing/SU

/MH • Counseling • Labs

1st PCP Visit • Medical

evaluation • ART criteria

met

ART start • Pills taken

Viral load suppressed • VL

monitoring • Adherence • Retention

Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.

RAPID Demonstration Project July 2013-December 2014

• Overall feasibility of a health systems intervention for same-day outpatient ART for newly diagnosed HIV infection

– Initially - new patients with acute HIV infection

– Extended in 2014 to include active opportunistic infection or CD4<200

• Deployed in context of extensive existing services for navigation, linkage and retention


8

RAPID Intervention Components

• Facilitation of same day appointments

• Flexible scheduling for providers (on-call back-up)

• ART regimens pre-approved for use prior to genotyping or lab testing

• Available as 5 day starter packs

• Accelerated process for health insurance initiation

• Recommendation for 1st dose to be taken observed in the clinic


New SFGH patients, RAPID era: 2013-4 Indicator RAPID Cohort (n=39) Universal ART

(n=47) P-value

Sociodemographics

Age: mean(range) 32 (21-47) 35 (19-68) NS

Male: n (%) 39 100% 43 92% NS

Non-white ethnicity 23 59% 34 71% NS

Homeless 11 28% 13 25% NS

Uninsured 39 100% 47 100% NS

Illicit Substance use 18 46% 18 38% NS

Staging

Acute (Ab- <6m) 21/30 70% 8/31 26% 0.001

Log10VL 4.9 (2.8-6.6) 4.5 (1.6-6.1) NS

CD4 mean (range) 474 (3-1391) 417 (11-1194) NS


RAPID: Uptake of Same-day ART

Days after ART offer/clinician visit

% on ART

90% 95%

0 1 7 30 0

0

10

20

30

40

50

60

70

80

90

100

RAPID

Universal


9

RAPID

Time to Viral Suppression by ART Initiation Strategy: SFGH 2006-2014

RAPID vs. universal ART P<0.001

Universal ART

CD4-guided ART

Proportion <200 copies


56 days 126 days

RAPID Safety Data

• INSTI based regimen in 87% (NS difference b/w arms) – Most common initial regimen in RAPID: TDF/FTC + DTG (67%)

• ART modifications more frequent among RAPID Arm – 2 ART changes due to rash

– 10 ART changes for simplification (e.g. to ABC/3TC/DTG)

– No changes for VF

– No changes after genotype results returned

• Transmitted Drug Resistance (n = 75 w/ genotype results) – 82% in RAPID versus 92% in non-RAPID obtained genotype (NS)

– 35% w/ any major resistance mutation

– 24% with NNRTI resistance mutation


Same Day ART (SDART)

• Randomized controlled trial to compare same-day ART versus standard

– Inclusion: Adult, ART Naïve, WHO stage 1 or 2, CD4 ≤ 500

– Exclusion: CXR c/w TB or Pneumonia, failed ART readiness survey

• Primary Outcome: Retention in care with VL < 50 c/mL @ 12 months

• Secondary Outcomes

– ART Initiation

– Survival

Koenig S et al. International AIDS Conference 2016. Durban, South Africa. Abstract WEAE0206LB

10

Schedule of Visits & Randomization

• Standard group – Days 7, 14, and 21: Physician/social

worker visits

– Day 21: ART initiation

– Week 5: Physician/social worker visits

• Same-day ART group – Day 1: Counseling and ART initiation

– Days 3, 10, and 17: Physician/social worker visits

– Day 24: Physician visit

• Only difference was timing of ART initiation

• 762 enrolled/randomized – 51 transferred and excluded

• April 2016 DSMB recommended publication

• Analysis includes 564 enrolled by Feb 2015


Standard vs. Same-day ART

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Completed CD4count

Initiated ART Alive and in Care at12 months

Alive withundetectable VL

100%

92%

71%

50%

100% 100%

80%

61%

Standard (285)

Same Day (Test /Treat) (279)


• 20 Ugandan Ministry of Health clinics

– , randomized in groups of 5

• Groups randomized in order to receive intervention

• Intervention: START-ART (Streamlined ART Start)

– Opinion-leader led training on benefits of ART

– Point-of-care CD4 assay

– Biannual feedback to the sites

Amanyire et al. Lancet HIV. 2016

11

START-ART

31 Amanyire et al. Lancet HIV. 2016

START-ART Secondary Outcomes

Intervention Control RR

ART Initiation

Same day 71% 18% 3.87 (3.64-4.11)

30 day 85% 57% 1.49 (1.46-1.53)

90 day 90% 70% 1.27 (1.25-1.30)

Viral Suppression 66% (85%) 58% (75%) 1.13 (1.02 – 1.27)

Survival 2% 3% NS

Retention 84% 84% NS

Amanyire et al. Lancet HIV. 2016

Real World Experience From a Ryan White

Funded Program in the South

12

Grady IDP: Who do We Serve?

• 6,008 unique patients in 2016

• Primarily patients with a diagnosis of AIDS

• 73% Male, 26% Female, 0.5% Trans

• 82% Black/African American, 14% White, 4% Latino

• 13% < 24, 37% 25-44, 50% >45 years of age

• 61% < FPL, 90% < 2X FPL

• 46% uninsured, 22% Medicaid, 20% Medicare

• 48% Heterosexual, 47% MSM, 7.5% perinatal, 5% PWID

Potential Barriers to Starting ART

• Structural / System – HIV testing/diagnosis occurs off site

(referrals to clinic)

– Complex eligibility criteria for clinic (CD4, income, residence)

– How to access to medications without payer source

– Scheduling

• Provider attitudes / beliefs – “That’s how we’ve always done it”

– Preparatory labs results (Creatinine, hepatitis serology, genotype)

– TB screening (PPD at our clinic)

• Patient attitudes / beliefs

• Patient social situation / comorbidities – Unstable housing

– Food insecurity

– Mental illness

– Substance use

NO

Waiting Area

YES Financial Counselor

Grady/RW Requirement ID, Residency, Income

NO

YES

Waiting Area Nurse Assessment

Verify CD4

> 200 OR None

< 200 (or other criteria)

PPD Status

Symptom Screen

CXR & Attdg Review

Thursday: Return

PPD Placed (M, T, W, F) None

PPD Read Waiting Area NEG

48 hrs

Education

List of required

docs

Refer to Health Dept

List of required

docs

POS

Patient arrival & check-in

PAR document

check

PAR: Give Appt

Date

NEG

Return for

Reading

Enrollment Process IDP July 2015

13

December 1, 2015: Phase I of Strategy to End AIDS in Fulton County

Objective #32: Increase proportion of

diagnosed persons linked to care within 3 days to

85%

Rapid Entry into HIV Care: May 16, 2016

• Changed eligibility criteria • CD4 criteria expanded • All patients from Grady system

• Softened document requirements for

RW and Grady • ID, Proof of income, Proof of residence

• Implemented Peer Counselor

• Removed PPD as hard stop

• Active tuberculosis screening • Continue to require PPD

• Revised provider templates

• Improved communication with

finance/pharmacy

Goals: (1) Facilitate appt within 72 hours of first step in clinic

(2) Decrease time to viral suppression

NO

Waiting Area

YES / NO Financial

Counselor

Grady/RW Requirement ID, Residency, Income

YES/NO Nurse Assessment

Symptom Screen

CXR & Attdg Review

PPD Read Waiting Area NEG Education

POS

Patient arrival & check-in

PAR document

check

PAR: Give Appt

Date

NEG

Enrollment Process IDP May 2016

Peer Navigator

14

Mr G Case Continued…

• Initial: CD4 25, VL 267,000 cml of HIV RNA

• Initiated ART on day of enrollment

• Virologically suppressed 21 days after enrollment

• Remains in care 9 months later • VS, CD 225

• No substance use for 8 months

• Engaged in care with Mental Health

• Housing through the Living Room

Rapid Enrollees May 16 – July 15, 2016 N = 100

Characteristic Number

Age, Median (IQR) 39 (27, 49)

≤ 24 yo 17

Gender

Male 78

Female 21

Trans (MtoF) 1

Insurance Status

Uninsured (RW) 59

Medicaid 20

Medicare 17

Private 4

Characteristic Number

Immunologic CD4 < 200 56 CD4 200 - 350 17 CD4 350 - 499 4 CD4 >= 500 20

New Enrollees and Days to Provider Visit

11 14

10

12 5 3 3 1

0

5

10

15

20

25

30

35

40

45

50

0

5

10

15

20

25

30

35

40

45

50

January February March April May(1st - 15th)

May(16th - 31st)

June July(1st - 15th)

Day

s

Enro

llees

New Enrollee Average days to provider visit

CD4 criteria loosened Expanded eligibility to partners of patients RAPID Entry

15

ART Initiation

• 8 excluded as transfers on ART

• 5 excluded because started in hospital

• 11 never made first visit

• 7 not started

– Research study, complex social situations, side effects to TMP/SMZ

69 Patients Prescribed ART @ IDP

ART Regimens: 74 Initiated

Drug Count % TDF 38 51% ABC 24 32% TAF 12 16%

Backbone Anchor Drug Count %

DTG 47 62% EVG 17 22% DRV 5 7% RPV 3 4% RAL 2 3% EFV 2 3%

87% INSTI

Time to ART Initiation (N=69)

Prescribed on initial visit 51 (74%)

Median Time to Rx (days) 1 (1,1)

Mean Time to Rx (days) 3.5 (SD 6)

Median Time to start (days) 1

Mean Time to start (days) 4.3 (SD 7)

1 = same day

Patient-Provider Decision

16

Time to Viral Suppression (VL < 1000)

2010 Enrollees

• 177 patients (VS at first recheck)

• Median starting VL 36,850 c/mL

Median Time to VS: 73 days

(IQR 55, 102)

RAPID Enrollees (2016)

• 25 patients with adequate follow-up

• Median starting VL 114,989 c/mL

(IQR 29,000 – 300,000)

Median Time to VS: 21 Days

(IQR 17, 34)

The Expanding

Toolkit

↓ Time to VS

&

↑ Retention and Continuous

VS

Patient Navigators

Rapid Entry

ARTAS

Reminder Calls

Substance use and mental

health services

Health Information

Exchange

Inpatient ART Start

Peer Counselors

Specialty (mail order) Pharmacy

Q4: Same day ART decreases time to viral suppression, but has no impact on mortality

A. TRUE

B. FALSE

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Conclusions

• Guidelines recommend ART for all – Morbidity and mortality benefits

– Decrease risk of transmission

• Starting ART as early as same day of diagnosis is safe and efficacious – Decrease time to viral suppression

– Improve retention in care (at 10 and 12 months)

– Decreases Mortality

• Creating systems for rapid entry into clinic is feasible in a Ryan White Funded setting

Acknowledgements

• Patients • Clinic Staff

– PARs – Nursing – Clinic Assistants – Providers – Phlebotomy – CWB – Dental

• Pharmacy – Techs – Pharmacists – PAAs

• Administration

• Carlos del Rio, MD • Wendy S Armstrong, MD • Jeri Sumitani, PA-C • Education / Enrollment Staff

– PARs – Financial department – Nursing – Peer Educators – Client Trackers – ARTAS team

P30AI050409

References

• CCO. Putting the DHHS HIV Treatment Guidelines Into Practice. January 2013. Available at https://www.clinicaloptions.com/HIV/Treatment%20Updates/DHHS%20Guidelines/Module/DHHS_Guidelines/Pages/Page%201.aspx. Accessed on 17 March 2017.

• Sax P. START is STOPPED: Study Confirms HIV Treatment Is Beneficial for All, Even Those with High CD4 Cell Counts. HIV and ID Observations: NEJM Journal Watch. May 27 2015.

• Cohen et al. Antiretroviral therapy for the prevention of HIV-1 Transmission. N Engl J Med 2016;375:830-9

• Cohen et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505

• INSIGHT START. Initiation of Antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373: 795-807

• TEMPRANO ANRS 12136 Study Group. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015; 373:808-22.

https://www.clinicaloptions.com/HIV/Treatment Updates/DHHS Guidelines/Module/DHHS_Guidelines/Pages/Page 1.aspx

https://www.clinicaloptions.com/HIV/Treatment Updates/DHHS Guidelines/Module/DHHS_Guidelines/Pages/Page 1.aspx

18

References (cont.)

• Rosen S, Maskew M, Fox MP, Nyoni C, Mongwenyana C, et al. (2016) Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial. PLoS Med 13(5): e1002015. doi:10.1371/journal.pmed.1002015 http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1002015

• Pilcher CD, Ospina-Norvell C, Dasgupta A, Jones D, Hartogensis W, Torres S, et al. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a U.S. Public Health Setting. J Acquir Immune Defic Syndr 2016.

• Koenig S, Dorvil N, Severe P, Riviere C, Faustin M, Perodin C, Paul C, Apollon A, Saintil G, Duverger L, Dumont E, Hedt-Gauthier B, Hennessey K, Rivera V, Devieux J, Pape JW. Same-day HIV testing and antiretroviral therapy initiation results in higher rates of treatment initiation and retention in care. 21st International AIDS Conference. Durban South Africa, 2016. Abstract WEAE0206LB.

• Amanyire G, Semitala FC, Namusobya J et al. Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomized trial. Lancet HIV 2016: 3: e539-48

http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1002015

Rapid Entry and ART Initiation in HIV Care: Implementation ... · N Engl J Med. 2015;373: 795-807; TEMPRANO ANRS 12136 Study Group. N Engl J Med. 2015; 373:808-22. Early ART led to

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