going the full 360: linkage to care and treatment - hiv.eu · linkage to care after hiv diagnosis...

Beyond Undetectable: Going the full 360 is organised and funded by Gilead Sciences Europe Ltd.Date of preparation: June 2019Job code: 001/IHQ/19-02//1076s

Going the full 360: Linkage to care and treatmentLaura Waters FRCP MD

Consultant Physician GU/HIV MedicineCNWL, Mortimer Market Centre, London

UNAIDS target: 90% of diagnosed PLHIVto be virally suppressed by 2020

90%

PLHIV, people living with HIV; UNAIDS, The Joint United Nations Programme on HIV/AIDS.

Adapted from UNAIDS. 90-90-90: an ambitious treatment target to help end the AIDS epidemic 2014. Available at http://www.unaids.org/sites/default/files/media_asset/90-90-90_en.pdf [Accessed June2019].

90% 90%

Diagnosed On treatment Virally suppressed

90%v

Where are we now?

Progress toward achieving the 2nd 90:90% of those diagnosed on ART (N=39)

ART, antiretroviral therapy; ECDC, European Centre for Disease Prevention and Control.

Noori T. Presented at: ECDC 2nd Update on Clinical Topics in Antiretroviral Therapy workshop Barcelona 2019. Available at: https://www.hivclinicaltopics.com/wp-content/uploads/2019/06/7.-How-to-reduce-HIV-incidence-in-Europe_NOORI_HIVClinicalTopic2019_FLS-Science.pdf [Accessed June 2019].

Target reached Above regional average Below regional average

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Global target 90%

Overall percentage 64%

Progress toward achieving the 2nd 90:Significant sub-regional variation: West, Centre, East

Brown AE et al. Euro Surveill 2018;23(48):1800622.

Range68-100% Range

50-85%

Range30-95%

Time from diagnosis to linkage to careimpacts progress towards the 2nd 90

PLHIV, people living with HIV; WHO, World Health Organization.

ECDC. HIV/AIDS Surveillance in Europe 2018 – 2017 data. Available at: https://ecdc.europa.eu/en/publications-data/hivaids-surveillance-europe-2018-2017-data [Accessed June 2019].

Centre

East

West

WHO EuropeanRegion

EU/EEA

0 20 40 60 80 100Percentage

Linkage to care after HIV diagnosis in the EU/EEA, WHO European Region and West, Centre and East, 2017 (N=26,147)

0–4 days 5–14 days 15–28 days 29–91 days 92–365 days > 365 days

Most are linked to care within 100 days, and regions linking to care more quickly are closer to achieving the 2nd 90 target

ART initiation policies in European countries 2014 (N=49)

ART, antiretroviral therapy; CD4, cluster of differentiation 4; ECDC, European Centre for Disease Prevention and Control.

ECDC. Dublin Declaration monitoring 2018. Available at: https://www.ecdc.europa.eu/sites/portal/files/documents/HIV-continuum-of-care-monitoring-dublin-declaration-progress-report-2018.pdf [Accessed June 2019].

4

16

28

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2014 2015 2016 2018

200 cells/μL 350 cells/μL 500 cells/μL Initiation regardless of CD4 count

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ART initiation policies in European countries 2014 (N=49)

ART, antiretroviral therapy; CD4, cluster of differentiation 4; ECDC, European Centre for Disease Prevention and Control; WHO, World Health Organization; EACS, European AIDS Clinical Society.


WHO. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. 2015. Geneva. Available at: https://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/ [Accessed June 2019].

EACS Guidelines 8.0. 2015. Available at: http://www.eacsociety.org/files/guidelines_8.0-english-revised_20160610.pdf [Accessed June 2019].

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ART initiation policies in European countries 2014 (N=49), 2016 (N=47)





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ART initiation policies in European countries 2014 (N=49), 2016 (N=47), 2018 (N=54)





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Barriers to linkage & attendance

Factors associated with delayed or no linkage to care after diagnosis

*Systematic review and meta analysis of 7 studies reporting delayed (>3 months) or no linkage to care after HIV diagnosis in the WHO European region 2006 to 2017.

Image credit: Avert.org

STI, sexually transmitted infection; VL, viral load; WHO, World Health Organization.

1. Croxford S et al. PLoS ONE 2018;13(2):e0192403. Image credit: Avert.org

Factors associated with delayed or no linkage to care after HIV diagnosis in the WHO European region1*

Being diagnosed in Central or Eastern Europe

Heterosexual transmission

Injection drug useYounger age at diagnosis/test

Lower educational levelLack of convenient access to a clinic

Lack of symptoms at diagnosis

Undetectable VL at diagnosis

Migrant statusDiagnosis outside STI clinic

No health insurance

In 2018, which countries provided access to ART for undocumented migrants?

ART, antiretroviral therapy.

1. Noori T. Update on clinical topics in antiretroviral therapy workshop. 30-31 May 2019. Barcelona, Spain; 2. Deblonde J et al. BMC Public Health. 2015;15:1228.

Yes No No response

Does immediate ART improve retention?

Intervention

Treat all PLHIVregardless of CD4 count

and clinical stage

Control

Treat all PLHIVaccording to South African guidelines

(≤350 CD4, WHO stage 3 or 4 until Dec 2014, ≤500 since Jan 2015)

TasP study with universal test and treatin South Africa

Objective: to evaluate impact of early ART on HIV incidence in general population in 22 cluster-randomised communities*

*The primary endpoint was HIV incidence, defined by seroconversion between repeated dried blood spot samples collected with this the population cohort every 6 months until 58 cluster years of follow up.

ART, antiretroviral therapy; TasP, treatment as prevention; WHO, World Health Organization.

Adapted from Iwuji CC et al. Lancet HIV 2018;5(3):PE116-E125.

6-monthly rounds of home-based HIV-testing

Phase 1

20142012 2016

Phase 2

ANRS 12249

No difference in population HIV incidence! Why?

Poor linkage and retention in care led to disappointing outcomes: 30% linked within 6 months

UNAIDS target1

UNAIDS, The Joint United Nations Programme on HIV/AIDS.

1. Adapted from UNAIDS. 90-90-90: an ambitious treatment target to help end the AIDS epidemic 2014. Available at http://www.unaids.org/sites/default/files/media_asset/90-90-90_en.pdf [Accessed June2019]; 2. Iwuji CC et al. Lancet HIV 2018;5(3):PE116-E125; 3. Iwuji C et al. Lancet HIV 2018;5(3):PE116-E125 Supplementary material [online]. Available at: https://www.thelancet.com/cms/10.1016/S2352-3018(17)30205-9/attachment/8e32a355-bf74-4e1c-bf9f-69fc6c5adde5/mmc1.pdf [Accessed June 2019].

ANRS 12249 estimated cascades2,3

=72.9%

Diagnosed

=44.4%Control 91.8%

=46.2%Intervention

Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence

91.1%

90%

On treatment

57.5%

58.5%

90%

Virally suppressed

84.1%

86.6%

90%

Universal test and treat programme with additional support for linkage to care

Community randomised trial in Zambia and South Africa (N=52,500)

ART, antiretroviral therapy; PopART, Population Effects of Antiretroviral Therapy to Reduce HIV Transmission.

Hayes RJ et al. Presented at 26th CROI. 4-7 March 2019. Seattle, USA. Available at: http://www.croiwebcasts.org/console/player/41195?mediaType=slideVideo&&crd_fl=1&ssmsrq=1560412392031&ctms=5000&csmsrq=3148 [Accessed June 2019].

Arm A

Arm B

Arm C

Full PopART interventionincluding

Immediate ART irrespective of CD4 count

PopART interventionexcept

initiation according to current national guidelines

Standard of care atcurrent service provision levels, including ART initiation according

to current national guidelines

2,500 random sample of each community

(aged 18–44);Followed up annually for

36 months

Community HIV-care providers supported

linkage to care, ART adherence and other

HIV services

Enhanced linkage to care support achieved90% diagnosed PLHIV on treatment

Viral suppression was achieved in all arms:

• 72%, 68% & 60% at 24 months in arm A, B, C, respectively (p=ns)

ART, antiretroviral therapy; ns, not significant; PLHIV, people living with HIV; PopART, Population Effects of Antiretroviral Therapy to Reduce HIV Transmission.

Hayes RJ et al. Presented at 26th CROI. 4-7 March 2019. Seattle, USA. Available at: http://www.croiwebcasts.org/console/player/41195?mediaType=slideVideo&&crd_fl=1&ssmsrq=1560412392031&ctms=5000&csmsrq=3148 [Accessed June 2019].

PopART w/ rapid ART vs standard care (arm A vs C):

PopART w/ standard ART start vs standard care (arm B vs C):

7% reduction in new HIV (p=0.51)

30% reduction in new HIV (p=0.006)

…but immediate ART initiation achieved unexpected results for arm A:

Achieved the first two 90s in arms A and B within 3 years

Community wide universal testing + efforts to link to care + immediate start ART offers progress in high burden areas

Rapid ART initiation can improveclinical outcomes

*ART start within 14 days of diagnosis.

ART, antiretroviral therapy; CI, confidence interval; RR, relative risk; LTFU, lost to follow up.

Adapted from Ford N et al. AIDS 2018;32(1):17–23.

Study Relative risk (95% CI)

Remaining in care

Koenig 1.11 (1.02, 1.21)

Amanyire 1.01 (0.94, 1.08)

Rosen 1.27 (1.12, 1.44)

Subtotal 1.11 (0.99, 1.26)

Outcomes from randomized trials comparing same day ART start vs standard of care at 12 months

ART start on the same day showed improvement in retention in care at 12 months (RR 1.11, 95% CI 0.99–1.26)

Study Relative risk (95% CI)

LTFU

Rosen 0.47 (0.23, 0.92)

Koenig 0.77 (0.57, 1.04)

Subtotal 0.66 (0.42, 1.04)

0.2 1 2 3

Standard care Same day ART0.2 1 2 3

Standard care Same day ART

…what about engagement and retention in care?

San Francisco RAPID ART initiationhas some inspiring results, but…

86 patients were treated on either a RAPID protocol (n=39), or non-rapid (n=47)

• Transfer to another HIV clinic: ⎼ Rapid: 20.5% (n=8)

⎼ Non-rapid: 23.4% (n=11)

• Loss to follow-up (p=0.52):⎼ Rapid: 10.3% (n=4)

⎼ Non-rapid: 14.9% (n=7)

ART, antiretroviral therapy.

Pilcher CD et al. J Acquir Immune Defic Syndr 2017;74(1):44–51.

Other mechanisms to improve retention

Barriers to linkage

Lessons learned from ANRS 12449 & POPART: low linkage at 1 year

Linkage & ART initiation within 12 months

• 53% in POPART, 58% in ANRS 12449

Identified barriers

• Inconvenient hours, overcrowded clinics, health providers’ poor attitude, stigma, shame

Lessons learned from a South African cohort (n=1482): impact of mental health• Depression 33% & anxiety 9% (by PHQ-9 and GAD-7)

• Delayed presentation (linkage >90 days after first positive HIV result:

Severe depression vs no depression: 3.6 greater odds (95% CI, 1.2-10.2) of delayed presentation

Generalised anxiety vs no anxiety: 2.3 greater odds (95% CI, 1.3-4.2) of delayed presentation

Rane MS et al. Clin Infect Dis. 2018 Oct 15;67(9):1411-1418.; Ayieko J et al. J Acquir Immune Defic Syndr. 2019;80(4):414–422.

SEARCH: Accelerated linkage to carein rural Uganda and Kenya

VL, viral load.

Adapted from Ayieko J et al. J Acquir Immune Defic Syndr. 2019;80(4):414–422.

Adult residents in intervention communities (n=88,627)

HIV negative (n=64,497)

HIV positive (n=6,811)

In care (n=4,760)Clinical records=4,435

VL<500=325

HIV positive not in care (n=2,051)

Not linked at one year (n=548)

Linked at one year (n=1,503)

Linked after tracking (n=607)

Linked spontaneously (n=896)

Tracking if linkage appointment was missed

Transport reimbursement

Appointment reminder phone call

Telephone “hot-line” for enquiries

Introduction to clinic staff after testing

Accelerated linkage to care interventions:

Tested for HIV (n=71,308)

Structured phone call within 1 hour of HIV test improved linkage to care

PLHIV, people living with HIV; RCT, randomised controlled trial.

Adapted from Ayieko J et al. Open Forum Infect Dis 2018;5(6):ofy126.

PLHIV were randomised to receive a structured phone call or no phone call within 1 hour of post-test counselling

SEARCH: Kenyan substudy

Among 130 PLHIV, those randomised to the structured phone call were significantly more likely to link to care by 7 and 30 days (P = 0.04)

208 participants

Randomisation

130 participants

Intervention 68 participants

Standard62 participants

40 not linked (59%) 15 linked (24%)28 linked (41%) 47 not linked (76%)

78 ineligible(linked before RCT or out

of care for <6 months)

REACH: A UK mixed methods study to investigate retention in outpatient HIV care

• Cross-sectional survey and interviews of PLHIV attending 7 London HIV clinics (May 2014 to August 2015)

Patients’ suggestions to improve engagement in HIV care included:

Promoting engagement in care (UK)

DNA, did not attend; PLHIV, people living with HIV.

Adapted from Howarth A et al. Health Serv Deliv Res 2017;5(13).

Pay transport in advance

Social support and advice in clinic

Text reminders and phone calls; pre-agreed action if DNA

Education to reduce stigma

Home visits/video consultations

‘Non-scolding’ reception staff

Information to signpost facilities

Dosette boxes as standard

Flexible opening hours and locations

The REACH study (UK) includeda very low-cost intervention

REACH: A UK mixed methods study to investigate retention in outpatient HIV care

*All costs are in 2015/16 GBP; Cost of the low-cost, clinic-wide intervention is a one-off cost per patient; The other costs are mean costs per patient over a 6-month period.

MDT, multidisciplinary team; NHS, National Health Service.

Adapted from Howarth A et al. Health Serv Deliv Res 2017;5(13).

Intervention Cost per patients (£)*

Structured peer involvement Six one-to-one sessions with peer worker

538

‘One stop’ weekly MDT clinic Incl. consultant, nurse specialist, psychologist, social worker, peer caseworker

398

Clinic in non-NHS/alternative NHS setting e.g. library, GP surgery or pharmacy

302

Low-cost clinic wide intervention 2

ALL STAFF reminding patientswhy it is important to attend

What we do locally

DNA, did not attend.Author’s experience.

Evening clinics

Phone and email clinic

Proactive DNA policy

Peer support

• Counselling patients

• Drivers of poor adherence

• How to improve adherence

• Future directions

Adherence

“But we’re good at predicting adherence!”

Signals

• Low-level viremia3

• Missed appointments/refills2

• Not running out of ART when expected2

ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis; TDM, therapeutic drug monitoring.

1. Boretzski J et al. Patient Prefer Adherence 2017;11:1897–1906; 2. Holtzman CW et al. Drugs 2015;75(5):445–454; 3. Maggiolo F et al. Pragmat Obs Res 2017;8:91–97.

No, we’re not!

Self-report may not be reliable1

• We’ve learned a lot from PrEP trials and from hair TDM

Acceptance

• Patient acceptance and understanding of ART informs adherence to treatment2

✓

Estimating adherence is a challenge

Concordance of physicians’ adherence assessment and patients’ self-reports

Adapted from Boretzski J et al. Patient Prefer Adherence 2017;11:1897–1906.

Physicians’ adherence assessment n (% of whole study group)

Patients’ self-reports, n (% of whole study group) N=214 Good Unstable/poor

No dose missed during the last week 145 (67.8) 25 (11.7)

One or more doses missed during the last week 17 (7.9) 27 (12.6)

Total 162 (75.7)a 52 (24.3)Note: aOne patient’s data was missing

80% concordance between physician assessment and patient-self report

Many reasons for suboptimal adherence in PLHIV

Cross-sectional, noninterventional, multicentre study in Germany to identify current reasons for nonadherence to ART. PLHIV were categorised by physicians as: good (n=162), unstable (n=36), and poor adherence (n=17)

*Reported significantly more often by people with unstable or poor vs. good adherence.

ART, antiretroviral therapy; PLHIV, people living with HIV.

Adapted from Boretzki J et al. Patient Prefer Adherence 2017;11:1897–1906.

Most frequently reported reasons for nonadherence (all groups):

Forgot

Reminder of disease*

Skipping meds when feeling bad or stressed*

Toxicity beliefs regarding alcohol or party drugs/going out*

Different daily routine

Afraid of being seen*

People with unstable or poor adherence also reported “financial constraints” and “no need for ART any more” as reasons for nonadherence

Reasons for poor adherence and possible solutions

ART, antiretroviral therapy; LA ART, long-acting ART.

1. Iacob SA et al. Front Pharmacol 2017;8:831; 2. Howarth A et al. Health Serv Deliv Res 2017;5(13); 3. Kardas et al. Front Pharmacol 2013;4:91; 4. DHHS guidelines 2018. Available at: https://aidsinfo.nih.gov/guidelines [Accessed June 2019].

BeliefsSide effects

Stigma/privacy

Accessing careDrug supply³Acute illness⁴

Forgetting

INTENTIONAL

UNINTENTIONAL

Education: clear, regular, accessible, peers,Detailed history, switch, reassurance

Simple ART, forgiveness, top tips (peers)²

SOLUTIONS?

Flexible appointments, transport assistance⁴Appropriate funding & infrastructure¹,⁴

Education, appropriate routeReminders, dosette², top tips (peers)², LA ART

SOLUTIONS?

DHHS: Linking patients to counselling to overcome stigma, substance use, or depression⁴

Guidance on considering adherence when starting ART

ART, antiretroviral therapy; DHHS, United States Department of Health & Human Services; DRV, darunavir; DTG, dolutegravir; EACS, European AIDS Clinical Society; INSTI, Integrase strand transfer inhibitors; PI, protease inhibitor; PLHIV, people living with HIV.

1. EACS Society. Guidelines 2018. Available at: http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdf [Accessed June 2019]; 2. DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV 2018. Available at: https://aidsinfo.nih.gov/guidelines [Accessed June 2019].

EACS:1 INSTI is preferred third agent for PLHIV starting ART; however, other classes (e.g boosted PI) might be indicated in people with risk of poor adherence

DHHS:2

• An individual’s barriers to adherence to ART and appointments should be assessed before initiation of ART and regularly thereafter

• People with ART adherence problems should be placed on regimens with high genetic barriers to resistance (e.g. DTG or boosted DRV)

• Side effects, convenience, and patient preferences also need to be considered

POORLY ADHERENT

A change of terminology

POORLY MANAGED

A change of terminology

Future directions

New technologies could improve diagnosis and linkage to care

McCracken KE and Yoon JY. Anal Methods 2016;8:6591-601. Published by The Royal Society of Chemistry.

New technologies could improve diagnosis and linkage to care

eDiagnostics

• Enables a move from point-of-care testing to eHealth diagnostic devices to connect patient with healthcare professionals and services

1. McCracken KE and Yoon JY. Anal Methods 2016;8:6591-601; 2. Cho S et al. Biosens Bioelectron 2015;15(74):601-11; 3. Dionysios CC et al. ACS Cent Sci 2018;4:1600−1616.

✓

Simple method of reaching PLHIV

PLHIV, people living with HIV.

Adapted from WorldoMeters U.N. data, GSMA Intelligence. Available at: https://www.bankmycell.com/blog/how-many-phones-are-in-the-world [Accessed June 2019].

66.72%of

own a cell phoneWORLDthe

Simple method of reaching PLHIV

PLHIV, people living with HIV.

Adapted from WorldoMeters U.N. data, GSMA Intelligence. Available at: https://www.bankmycell.com/blog/how-many-phones-are-in-the-world [Accessed June 2019].

66.72%of

own a cell phoneWORLDthe

82.2% in UAE 5.4% in Bangladesh

Smartphone Penetration % <14 14–28 28–42 42–56 >56

Linkage to care and treatment:Conclusions

ART, antiretroviral therapy; PLHIV, people living with HIV; TasP, treatment as prevention; UNAIDS, The Joint United Nations Programme on HIV/AIDS.

Author’s personal opinion.

Significant progress has been made towards achieving UNAIDS 90-90-90, but more can be done to ensure PLHIV start and stay on effective treatment

Rapid initiation of ART and TasP programmes must be underpinned by interventions to facilitate access and retention in care

Barriers to adherence should be assessed before initiating treatment and regularly thereafter

New smartphone-based technologies show promise for improving diagnosis and linkage to care

Thank you!

[email protected]

@drlaurajwaters

mailto:[email protected]

Thank you

going the full 360: linkage to care and treatment - hiv.eu · linkage to care after hiv diagnosis...

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