1
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
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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.
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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
Rosen S et al. PLoS Med 2016.
17 days
0 days
The Hope for Better Long Term Outcomes
Rosen S et al. PLoS Med 2016.
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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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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
Pilcher CD. et al. J Acquir Immune Defic Syndr 2016.
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
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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
Koenig S et al. International AIDS Conference 2016. Durban, South Africa. Abstract WEAE0206LB
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)
Koenig S et al. International AIDS Conference 2016. Durban, South Africa. Abstract WEAE0206LB
• 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
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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
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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
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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
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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
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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
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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.
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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