WHO Consolidated Guidelines on HIV Testing Services what

WHO Consolidated Guidelines on HIV Testing Services: what you need to know Dr. Rachel Baggaley & Cheryl Johnson WHO HIV Dept. Geneva , Key Populations & Innovative Prevention Unit 1 December 2015 ICASA Harare, Zimbabwe

600 M individuals (15+) received HTS across 122 low- and middle-income countries, from 2010 to 2014 Nearly half of all reported HTS delivered in the WHO African region. Source: GARPR (WHO, UNAIDS, UNICEF) 6 July 2015.

More than 150 million children and adults were reported to receive HIV testing services across 129 low- and middle-income countries in 2014. Source: GARPR (WHO, UNAIDS, UNICEF) 6 July 2015.

Women comprise nearly 70% of those tested in 2014 Majority of testing in ANC even in low and concentrated epidemics

In 2014, approximately 3 million children & adults tested HIV-positive in 81 LMIC reporting on HIV-positive tests Majority of the reported HIVpositive tests occur in the WHO African region Positivity Positives Rate Countries Tested 49, 242, 23 5 2, 580, 110 5. 2% Source: GARPR 6 July 2014; 81 low and middle-income countries reporting both adults and children who tested HIV-positive in 2014. Important to note this is not equivalent to new infections or HIV-prevalence as it includes re-testers and known positives. GARPR 6 July 2015 , select countries GARPR (WHO, UNAIDS; UNICEF); HIV prevalence estimates accessed 7 July 2015 UNAIDSinfo. org 30

Approximately 2 million people (15+) tested HIV-positive, in 2014 Outside of Africa, those who tested HIVpositive were more likely to be men in all regions Source: GARPR (WHO, UNAIDS, UNICEF) 6 July 2015. 65 countries reporting men and women tested HIV-positive and received their results, in 2014. Important to note this is not equivalent to new infections or HIV-prevalence as it

United Republic of Tanzania Estimated national HIV prevalence is 5%. Nearly 2. 5 million adult men and women received HIV testing services and 11% tested HIVpositive in 20142. Majority adults receiving HIV testing services were women— the proportion of adult men testing HIV-positive was 13% compared to 10% Women adult among Total Adults 15+ Men women 2. 935, 828 1, 533, 182 2, 469, 01 Total tested Tested HIVpositive 124, 606 155, 463 Source: GARPR 6 July 2015 , select countries GARPR (WHO, UNAIDS; UNICEF); HIV prevalence estimates accessed 7 July 2015 UNAIDSinfo. org 0 15, 990

Botswana Estimated national HIV prevalence is 22%. Over 300, 000 adult men and women received HIV testing services and nearly 7% tested HIV-positive in 20142. Adult men were 2 x less likely to receive HIV testing services than adult women—but the proportion of men testing HIV-positive was slightly higher Adults 15+ Men Wome Total 8% compared to 7% 2. n Total tested 107, 56 207, 622 315, 18 3 5 Tested HIV- 8, 132 13, 866 21, 998 positive Source: GARPR 6 July 2015 , select countries GARPR (WHO, UNAIDS; UNICEF); HIV prevalence estimates accessed 7 July 2015 UNAIDSinfo. org

Rational for HTS Guidelines The 1 st “ 90” is the most problematic Nearly half all people w/ HIV unaware of HIV status, globally • ↓ men, adolescents, key populations Suboptimal linkage post HTS to ART • People delay & still initiate ART late More focus and targeting • Balance between HTS approaches in low &

§ Critical Issues addressed in New HTS Guidelines Strategic choices § Making tough choices about mix of testing approaches, for better cost effectiveness, earlier diagnosis and linkage and impact - including ANC testing in different epidemic setting § Reinforcing appropriate testing in specific clinical settings & for indicator conditions § Increasing access by supporting community testing § Prioritizing index partner and family testing § New approaches §Trained lay providers testing (new recommendation) §Test for Triage (new testing strategy) §HIV self-testing (push for implementation and monitoring) § Preventing misdiagnosis §Focus on QA §Re-emphasise re-testing all +ve before ART initiation

Overview Consolidated HTS Guidelines Summary 1. Introduction & Key issues 2. Methodology 3. Pre and post-test services 4. Service delivery approaches 5. Priority groups • Infants & Children; Adolescents; Pregnant women; Couples & partners; Men; Key Populations; and Vulnerable/other populations 6. Strategic planning for HTS 7. Diagnostics for HIV diagnosis 8. Quality assurance of HIV testing 9. HIV testing in the context pf surveillance Background work • Review lay providers testing services • Test for Triage • Review of community based HTS for general populations • Review of community based HTS for KP • Costing of different HTS approaches • Cost-effectiveness of PITC in ANC in different prevalence settings • Misdiagnosis of HIV status report • Lit review of V&P around HIVST among KP

Lay providers— any person who performs functions related to health-care delivery and has been trained to deliver specific services but has received no formal professional or a paraprofessional certificate or tertiary education degree. Source: WHO 2013, WHO 2015

Lay provider HIV testing services Many country policies already permit lay provider HIV testing and pre-and post-test counselling; however task sharing can be expanded. Total Policies, 48 Countries Source: Flynn et al ; WHO 2015 WHO African Region, 25 Countries

New Recommendation Should trained lay providers perform HIV testing services using HIV rapid diagnostic tests? Studies identified: 1 RCT, 4 observational studies & 6 studies on values & preferences Increased Uptake • Uptake among ED patients was 57% (1, 382/2, 446) in the lay provider arm compared with 27% in the healthcare provider arm (643/2, 409; RR: 2. 12, 95% CI: 1. 96 to 2. 28) Quality & Accuracy equivalent to health workers with longer training • • 3 observational studies report lay provider and laboratory staff test results were concordant in nearly all cases 2 observational studies comparing lay provider and laboratory staff test results, sensitivity was calculated as 98. 0% (95% CI: 96. 3 - 98. 9%) and 99. 6%, and specificity was calculated as 99. 6% (95% CI: 99. 4 -99. 7%) and 100. 0%. Values & Preferences • General support for lay providers conducting HTS, particularly in RCT & other study measuring preferences among people who had actually undergone HTS with a lay provider. Cost • Cost of trained lay providers vary but are generally lower than cost of health providers with Trained lay providers can safely and effectively perform HIV longer training. testing services using rapid diagnostic tests. (strong recommendation, moderate quality evidence)

Considerations for success • Choose wisely –select and train lay providers wellmatched to clientele • Ongoing training, mentoring and support is key— having a quality assurance system is place is essential • Adequate remuneration – trained lay providers should receive adequate compensation • National policies need to establish a role for trained lay providers to perform HTS • Policies should permit trained lay providers to collect specimens, perform HIV RDTs, interpret test results, issue an HIV status to clients give pre-test information and post-test counselling, and support linkages to prevention, care and

Test for Triage • A single rapid diagnostic test in community-based HIV testing • Not a definitive test for those who test +ve • Emphasis on HIV diagnosis at health facility (start at A 1) • Triage – prioritize linkage following testing as appropriate Perform test for triage A 0 + Link to HIV testing for diagnosis, care & treatment A 0 – Report HIVRecommend repeat testing as needed

HTS Quality / Misdiagnosis National Testing Policies in Line with WHO Recommendations 48 Countries Review identified reports of misclassification range from 2. 6% to 10. 5%1, 2 Source: 1. Shanks PLo. S One 2013; 2. Klarkowski PLo. S One 2009; WHO 2015 Studies (N=44) Identified in a Literature Review, Reporting Factors Related to Misdiagnosis Category Clerical/technical errors (e. g. mis-labelling, poor recordkeeping, clerical mistakes) User error (e. g. errors performing RDT or interpreting results, misapplication of buffer, inaccurate reading time and other human errors) Cross-reactivity (e. g. antibodies from intercurrent infection, environmental exposure to test components, HIV subtype, or late-stage AIDS) Incorrect / suboptimal testing strategy or algorithm (e. g. tiebreaker testing strategy) Poor management and supervision (work load stress, staff shortages, lack of training, poor adherence to testing strategy or testing algorithm, substandard operating procedures, testing in window period) # 14 % 32% 11 48% 8 18% 22 50% 20 45%

WHO Retesting Recommendations infection 1. Retesting HIV-negative people at on-going risk for HIV • • • people from key populations people with a known HIV-positive partner people with known recent HIV exposure pregnant and breastfeeding women in high incidence/prevalence settings individuals seen for a diagnosis or treatment of STIs TB patients with a possible recent HIV exposure or who are at higher risk for HIV exposure • outpatients with clinical conditions indicative of HIV infection It is important to note that in low prevalence settings retesting of pregnant women is not recommended, unless they are from a key population group or is known to have an HIV-positive partner. 2. Retesting people with HIV-inconclusive test results after 14 days; and 3. Retest to verify an HIV-positive diagnosis before initiating care and/or ART. • Retesting people who are already on ART is not recommended.

12 Quality System Essentials To assure the quality of HIV testing services it is critical that all sites follow 12 QSEs—regardless of whether HTS takes place in laboratories, facilities or in community-based

Focused HTS • Strategic use of PITC in low and concentrated epidemics • Where to stop testing and reprioritize • Focusing on diagnosing the undiagnosed, underserved & those with ongoing risk • Strategies to reach men • Overcome reluctance to provide partner testing /index partner testing • Legitimize lay provider/peer testing for outreach, esp. for KP Effective Focused PITC Generalized epidemics PITC in every health contact Low and Conc epidemics PITC in select services (TB, STI, Key pops) Couples and Partner Testing Generalized epidemics - offer to all Low and Conc epidemics - offer to partners of +ves Community Approaches Generalized epidemics - outreach for key pops, consider door to door, workplace, schools augmented Low and Conc epidemics - outreach to key pops

Community-Based HTS ✔ Highly Acceptable • Home based 82% (#18) • Index partner 93% (#6) • Mobile/outreach 93% (#9) • Earlier Workplace 59% (#4) Linkage to Care • Highly variable and problematic Source : Suthar 2914; WHO 2014 ? ✔ Diagnosis • 11 studies (3190 participants) CD 4 >350 cells- pooled 59%. Positivity Rate ? • Home based • Campaigns • KP outreach • Index partner ✔ Missing Populations • Men • Key Populations • Young women (not pregnant) Unit Cost • ? But cost effectiveness may be acceptable especially for KP

Cost per case detected & proportion HIV-positive LMIC settings (US$ 2013) Source: WHO 2015

Cost-effectiveness of Universal HTS For Pregnant Women (per 1 000 pregnant women) Source: WHO 2015; Ishikawa et al 2015

Why talk about HIVST? UNAIDS “ 90 -90 -90”

urrent WHO guidance on HIVST Many models, priorities and policy issues, and evidence gaps Outlines the issues & technical considerations for HIVST & encourages countries to conduct demonstration projects Normative guidance on HIVST is planned for 2016 Most current information available on HIVST. org WHO 2015 GL: http: //apps. who. int/iris/bitstream/10665/179870/1/9789241508926_eng. pdf? ua=1&ua=1

What is self-testing? Collects Perform Interpret s s

What is HIV Self-Testing (HIVST)? Reactive results need confirmation by health provider

Available Formally …& Informally Credits: David Stanton, Vincent Wong, Cheryl Johnson, Matthew Rosenthal

Current Policy Environment Policies & Product(s) Approved for HIVST Policies Explicitly Allowing HIVST Policies Under Development HIVST Available Informally USA 2012 Australia South Africa* China UK 2015 Kenya Zimbabwe Namibia France 2015 Hong Kong SAR Zambia South Africa Macau SAR Peru Russian Federation Malawi Thailand United Republic of Tanzania Rwanda Namibia Nigeria Source: UNITAID 2015 Brazil Ukraine

Products with regulatory approvals Product (supplier) Specimen Business Objectives Regulator y Status Other RDTs from Manufacturer Autotest VIH (AAZ, France)+ Whole Blood Sell in France, other EU countries, & Africa CE marked • Sure. Check HIV-1/2 Biosure HIV Self Test (Biosure, UK) Whole Blood Sell in UK, & Europe, international roll out planned CE marked • Sure. Check HIV-1/2 Ora. Quick In. Oral Fluid Sell in USA, Home HIV Test Europe, Latin (Ora. Sure America, Africa Technologies, Only 3 RDTs for HIVST are approved by a USA) FDA • Ora. Quick ADVANCE HIV -1/2 • Ora. Quick HIV ½ Rapid test regulatory authority, test • Ora. Quick HCV Rapid stringent but none WHO prequalified —work is underway provide clear guidance on steps to be taken. Many RDTs for HIVST are under development— 15 different manufacturers identified. 2015 Source: UNITAID

What we know? HIVST. org

Acceptability & Willingness Source: 1 www. hivst. org , Evidence Map, accessed 1 July 2015 – 42 reporting studies

Uptake Amongst All Residents in Malawi Since HIVST Made Available Highest uptake among adolescents Year 1 Year 2 Women Men • 76% in months 1 -12 • 74% in months 13 -24 • 44% first-time testers • ~90% returned kits with self-completed questionnaire Months 16 -19 Source: Choko et al forthcoming 2015 20 -29 30 -39 40 -49 Age Group (years) 50+

Increased Frequency of Testing among MSM In Brazil, MSM who were less frequent testers and considered testing but failed to test were more likely to prefer HIVST. In Australia 2/3 HIV-negative MSM said they’d test more frequently if HIVST was available. Models suggest increases in frequency using HIVST among MSM, especially in settings with low testing coverage, could have a public health impact. Source: Lippman 2011; Gray 2013; Venetuneac 2009; Katz 2015 HIVST increased frequency of HTS among MSM in USA

Accuracy can be good, but not As high as 98. 8% sensitivity and 100% specificity, always but depends on RDT used, IFUs, populations and settings

Linkage Evidence is limited, but promising 1, 2 • Especially when coupled with a proactive approach (e. g. home-based ART initiation) Higher ART among Home Self-test Clusters than Facility-based Mac. Pherson 2014 (Malawi) Parent Trial Participants • 80 -100% of MSM report they would link to further testing and care, if they had a reactive self-test result 3 Home-Based Test Facility-Based Test Home Group or Home Option (8, 194) Facility Group or Facility-Based (8, 466) 181 Participants initiating ART 8, 013 Participants not initiating ART Source: 1 Mac. Pherson 2014; 2 Choko 2014; 3. Figueroa et al. 2015 63 Participants initiating ART 8, 403 Participants not initiating ART

Adverse Events No serious adverse events as a result of self-testing for multiple diseases and conditions, including HIV, reported in published literature 1. Monitoring and reporting systems are few, important to develop and implement such systems. Some potential issues identified so far: • Couples report that discordant self-test result can be challenging 5, 6 and though few emerging reports of IPV— but primarily among couples with a history of IPV 4. • In Blantyre, ~3% of people felt coerced/persuaded— however nearly all said they would recommend HIVST to others 4, 5, 6. Source: 1 Brown et al 2014; 2 Carballo-Dieguez 2012: 3 Katz 2012; 4 Desmond 2014: 5. Kumwenda 2014; 6 Choko 2015

PSI/UNITAID STAR Project Catalysing HIVST in Southern Africa Implementation-research Partnership Tackling Market Barriers by: • Multiple sites, models, & populations • Normalizing HIVST in Southern Africa • Providing evidence for scale-up • Developing WHO Guidelines • Encouraging policy change • Enabling the regulatory environment • Shaping market to reduce barriers & increase entry of lowcost HIVST products available for purchase & on recommended diagnostic commodities list Source: WHO, 2015 http: //www. who. int/hiv/mediacentre/news/unitaid_hiv-self-testing/en/

Conclusions Current HIV testing services are not enough to get to 90. Strategic approaches are needed in combination to expand HTS, including increasing scope of work of lay providers, community-based HTS, outreach to key populations, and testing for couples/partners Public health response lags behind public demand—and we need to catch up. Self-testing is not new. But it is an additional tool to create demand for, not substitute, HIV testing services. WHO guidance on HIVST on the way, and implementation research underway Get going & Think big! We need visionaries & champions; we need to stimulate technological advances, better tests & innovations in implementation

Acknowledgements Slides prepared with special thanks to: Carmen Figueroa, Theresa Babovic, Michel Beusenberg, Daniel Low-Beer, Anita Sands, Irena Prat (WHO HIV Dept), Frank Lule, Buhle Ncube, Fabiran Ndenzako (WHO AFRO), Elizabeth Marum (CDC), Vincent Wong (USAID), Augustine Choko and Elizabeth Corbett (MLW, LSHTM) Special thanks to everyone who assisted with developing the guidelines: Steering Committee, Guideline Development Group, 120+ peer reviewers, all contributors of case examples, editors, designers, administrative, communications and technical support teams. Funding of the guidelines provided by PEPFAR (USAID & CDC) and UBRAF, as well as additional support on HIVST by UNITAID and BMGF.