HIV Pre- Exposure Prophylaxis

HIV Pre- Exposure Prophylaxis KNOWLEDGE AND ATTITUDES IN NORTH QUEENSLAND GENERAL PRACTITIONERS Principle Investigator: William Lane Co-Supervisor 1: Professor Clare Heal Co-Supervisor 2: Dr Jennifer Banks

HIV Pre-Exposure Prophylaxis (PrEP) Truvada = emtricitabine + tenofovir 4

Primary Care Physician Attitudes Regarding Human Immunodeficiency Virus Pre-Exposure Prophylaxis A Systematic Review Lane. W, Heal. C, Hargoven. S, Banks. J

Methodology Systematic review of data according to PRISMA guidelines Registered with PROSPERO Databases searched include: MEDLINE CIHNAL SCOPUS COCHRANE

Included Eligibility Screening Identification Records identified through database searching (n = 1148 ) Additional records identified through other sources (n = 0 ) Records after duplicates removed (n = 773 ) Records screened (n = 773 ) Records excluded (n = 731 ) Full-text articles assessed for eligibility (n = 42 ) Studies included in qualitative synthesis (n = 2 ) Studies included in quantitative synthesis (meta-analysis) (n = 5 ) Full-text articles excluded, with reasons (n = 35 ) - Participants not general practitioners or family physicians, or results not isolating specific profession results. n = 8 - Studies not assessing attitudes or perceptions n = 8 - Review articles, case commentaries and opinion pieces n = 6 - Guidelines to PrEP use n = 4 - Articles pertaining to HIV PEP and managing patients already infected with HIV n = 3 - Patient perspectives n = 2 - HIV risk factors n = 2 - HIV vaccination n = 1

Study Year, Location Type of Study Number of Participants Method Broad Themes Uncovered in Analysis Significant Risk Factors Arnold, 2012, United States of America (10) Qualitative study 22 Physicians In depth interviews in 3 cities in California Little consensus on PrEP target populations Most providers felt that PrEP be provided in primary care setting Providers expressed a need to build capacity to prescribe PrEP training, referrals and establishing reimbursement levels for care and drugs Concerns about monitoring adherence, side effects and toxicities, resistance and risk compensation among PrEP patients Providers believed in the public health benefits of PrEP Most agreed that serodiscordant couples were ideal candidates Low demand from their patients towards PrEP Identified cost as an issue No risk factors statistically established Krakower, 2017, United States of America (13) Qualitative study 31 Physicians Semi-structured qualitative interviews with 31 primary care physicians in Boston, Massachusetts Physician prescribing: risk stratification of patients important for prescribing and patient preferences Areas identified in uncertainty in prescribing PrEP - Report low risk behaviours and request PrEP - High risk for HIV and anticipated to have poor adherence Bacon, 2017, United States of America (11) Quantitative cross-sectional analysis 99 Physicians 20 item electronic structured questionnaire was emailed to PCPs -92% heard Do of not PrEP follow monitoring recommendations while using PrEP 26% prescribed PrEP Generalists 70% very or have somewhat limited confident knowledge to prescribe and experience PrEP of PrEP compared to HIV specialists 92% would prescribe to serodiscordant couples Physician concerns regarding PrEP: - Toxicity/side effects (75%) Caring for HIV infected patients results in increased willingness to prescribe PrEP (adjusted odds ratio 4.76, CI 95%: 1.43-15.76, P=0.01) - Resistance (60%) - Adherence (58%) - Drug cost (53%) - Increased sexual risk taking (41%) - Reimbursement/workload (19%) Training topics requested to cover: - HIV frequency testing (88%) - Contraindications to PrEP (86%) - Lab testing (86%) - PrEP eligibility (84%) - Adherence counselling (81%) - HIV testing type (69%) - Side effects/toxicity (69%) - Insurance (66%) - Sexual behaviour counselling (52%)

Hakre, 2016, United States of America (12) Quantitative cross-sectional 404 Physicians 20 item MCQ and short answer survey 53% had high knowledge level 5% prescribed PrEP 62% rated PrEP knowledge as poor 76% had never prescribed PrEP or PEP Who should be prescribed HIV PrEP - Serodiscordant partner (90%) Ever prescribed PrEP associated with PrEP knowledge (adjusted odds ratio 2.37, CI 95%: 1.27-4.42, P=<0.0065 - HIV infected patients not on ART (85%) - HIV infected patients on ART (69%) - Men who have sex with men (49%) - Sexually transmitted infections (35%) - Multiple partners (31%) Mimiaga, 2014, United States of America (6) Quantitative Cross-Sectional Analysis 115 Physicians Cross-sectional survey analysis Awareness of iprex and CAPRISA studies was 60.5% HIV specialists had more knowledge of PrEP compared to physicians Factors associated with lower odds of prescribing PrEP (p 0.05) - Data demonstrating >80% efficacy - Beliefs that behavioural interventions are safer/more effective - Concerns regarding efficacy/safety Smith, 2016, United States of America (14) Series of cross-sectional cohort studies 2009 n= 1500 2010 n=1504 2012 n=1503 2013 n=1507 2014 n=1508 2015 n=1501 - Decrease in funds for other prevention modalities Cross-sectional survey analysis Heard of PrEP (48%) Willingness to prescribe Prep to: - PWID (62%) - MSM (68%) - Patient who has an STD (32% Previous experience with ART (adjusted OR 1.07, CI 95%: 1.06-1.09) - Patient who has frequent partner change (56%) - Serodiscordant couples (80%) White, 2012, United States of America (15) Pre- and post- intervention quantitative cross-sectional analysis Pre-iPrEx n=178 Post-iPrEx n=115 Cross-sectional survey analysis PrEP knowledge increased post iprex study (36% 83%) p <0.01 Willingness to prescribe to: - Serodisordant couples (60%) - Sex workers (26%) Barriers to uptake: - Side effects (88%) - Concerns regarding efficacy (72%) - Resistance (88%) - Increased sexual risk taking (33%) - Cost (21%) - Increased workload (23%) Formalised guidelines for HIV PrEP use recommended

Downs and Black (Quantitative Studies) Study 1 2 4 5 6 7 8 9 10 12 13 14 15 16 17 18 20 21 22 23 24 25 26 27 Grade 3 11 19 Bacon Y Y Y Y Y Y Y N Y Y Y Y Y UT N N N Y Y Y UT N N Y N FAIR (11) D N D Y Hakre N Y Y Y Y Y Y N Y Y Y N N N N Y Y Y Y N Y UT UT Y N FAIR (12) Y D D UT D White N Y Y Y Y Y Y N N Y Y N N N N UT Y Y Y Y N Y UT UT Y UT N FAIR (15) D D D D Mimiaga Y Y N Y N N N N N N Y Y N N N N N Y Y Y UT N UT Y Y N LOW (6) N D D Smith Y Y Y Y Y Y Y N Y Y Y Y Y UT N Y Y Y Y Y N N N Y Y FAIR (14) D Y N COREQ (Qualitative Studies) Study 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Krakower NA 297 NA 297 297 NA NA 298 298 NA 298 NA NA NA (13) 297 Arnold (10) 2 NA NA NA NA 2 NA NA 2 2 2 2 NA 2 NA 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 Grade 298 298 NA 298 298 298 NA 298 298 298 298 NA 299, 301, 302 302 Fair NA 300, 301, 302 302 2 2 3 3 2 2 3 3 3 3 3 NA 3, 4, 5 3, 4, 5, 3, 4, 5 5 Fair NA 6 6

Results - Attitude Attitudes were generally positive Varying confidence and comfort with prescription of PrEP Association with knowledge and PrEP and positive attitudes Literature suggested a passive approach of doctors to the PrEP intervention

Results Barriers to uptake Side effect profile and unknown characteristics of PrEP were major barriers Study N= Barriers to Uptake % Side Effects Limited Data of PrEP Clinical Efficacy Development of Resistance Increase in Risk Behaviours among PrEP Users Cost of Medication Unsure of indications without clear evidence Increased Workload White(15) 46 88% 72% 88% 33% 21% N/A 23% Hakre (12) 225 67% 51% 25% 23% 28% 60% N/A Bacon(11) 99 75% N/A 60% 41% 53% N/A 19%

Results Future Recommendations Willing to undertake further training Formalised guidelines would increase confidence with PrEP prescription Study % Participants wanting further training Topics for Training (%) HIV Testing Frequency Contraindications to PrEP Use Laboratory Monitoring PrEP Eligibility Adherence Counselling Side Effects Sexual Behaviour Counselling Bacon (11) 67% 88% 86% 86% 84% 84% 74% 55% Smith (14) 83% 73% N/A 59% 73% 53% 59% 57%

Discussion Low exposure rates might account for lack of knowledge Overall positive attitudes towards intervention Education to improve the uptake of PrEP by primary care physicians No guidelines present for its prescription at the time of these studies formalised guidelines to improve confidence and prescription

HIV PrEP: Knowledge and attitudes in North Queensland General Practitioners PRINCIPLE INVESTIGATOR: WILLIAM LANE CO-INVESTIGATOR: PROFESSOR CLARE HEAL CO-INVESTIGATOR: DR JENNIFER BANKS

Assess emergency HIV PEP accuracy through retrospective chart analysis and prospective analysis post intervention Quantitative Research Assess knowledge and attitudes of GPs toward HIV PrEP through questionnaire Assess knowledge and attitudes of Emergency Department Staff toward HIV PEP through questionnaire

Knowledge of general practitioners towards PrEP Qualitative Research Nature of prescribing HIV PrEP Attitudes of General Practitioners towards PrEP

Assess emergency HIV PEP accuracy through retrospective chart analysis and prospective analysis post intervention Quantitative Research Assess knowledge and attitudes of GPs toward HIV PrEP through questionnaire Assess knowledge and attitudes of Emergency Department Staff toward HIV PEP through questionnaire

Quantitative Assess knowledge and attitudes of GPs toward HIV PrEP through questionnaire Qualitative Assess knowledge and attitudes of GPs toward HIV PrEP through individual in-depth interviews

QUANTITATIVE Database creation: 109 GPs Questionnaire Content validity assured Pilot study completed QUALITATIVE Iterative process Snowball sampling Multi-question semi-structured individual indepth interviews

Submitted to the QLD health HREC committee Low Negligence Risk Reference number: HREC/17/QTHS/16 Approval on the 16 th May 2017

QUANTITATIVE SPSS for windows release 24 Generate descriptive statistics Generate frequency tabulations QUALITATIVE Iterative process NVIVO version 11 for windows Identify underlying themes and issues

Demographics 41.1% response rate Median age of 44 Interquartile range 22 Median of 10 years experience in general practitioners Interquartile range 25

AWARENESS OF PREP 33.3% (15/45) never heard of PrEP 51.1% (23/45) knew little about PrEP 6.7% (3/45) had read studies 2.2% (1/45) had previously prescribed PrEP CONFIDENCE WITH PRESCRIBING PREP 71.4% (30/42) - not at all confident prescribing PrEP 19% (8/42)- slightly confident 7.1% (3/42) - neutral 2.4% (1/42) - confident

KNOWLEDGE OF PREP Method of use 24.4% correct PrEP efficacy 37.8% correct HIV PREVENTION DISCUSSIONS 74.5% (32/43) agree or strongly agree 4.7% (2/43)- disagree or strongly disagree 21% (9/43) - neutral stance

Not at all concerned Slightly concerned Neutral Moderately concerned Very Concerned Prescription of PrEP 9/45 20% 3/45 6.7% 12/45 26.7% 11/45 24.4% 10/45 22.2% Lack of guidelines 2/45 4.4% 8/45 17.8% 6/45 13.3% 14/45 31.1% 15/45 33.3% Increase risky behaviour 12/45 26.7% 7/45 15.6% 18/45 40% 4/45 8.9% 4/45 8.9% Resistance 6/45 13.3% 14/45 31.1% 16/45 35.6% 6.45 13.3% 3/45 6.7% Lack of PrEP trials * 7/44 15.6% 4/44 8.9% 24/44 53.3% 7/44 15.6% 2/44 2.5% Cost 9/45 15.6% 4/45 8.9% 21/45 46.7% 3 6.7% 5/45 11.1% Patient accessibility 7/45 15.6% 9/45 20% 15/45 33.3% 9/45 20% 2 4.4% Side effects 6/45 13.3% 9/45 20% 18/45 40% 6/45 13.3% 3/45 6.7% Inexperience prescribing antiretroviral 4/45 8.9% 4/45 8.9% 6/45 13.3% 13/45 28.9% 16/45 35.6% Daily dosing 3/45 6.7% 10/45 22.2% 20/45 44.4% 5/45 11.1% 5/45 11.1%

Highly unlikely Unlikely Neutral Likely Very likely MSM sex condomless 0/45 0% 3/45 6.7% 5/45 11.1% 13/45 28.9% 22/45 48.9% MSM sex with condom 1/45 2.2% 4/45 8.9% 17/45 37.8% 10/45 22.2% 11/45 24.4% Multiple partners (>10/year) 3/45 6.7% 13/45 31.1% 18/45 40% 7/45 15.6% 3/45 6.7% Injecting drug user 0/45 0% 9/45 20% 17/45 37.8% 10/45 22.2% 9/45 20% Serodiscordant couple 0/45 0% 1/45 2.2% 9/45 20% 12/45 26.7% 23/45 51.1%

Not at all important Low importance Neutral Moderately important Very important Evidence of efficacy 3/45 6.7% 1/45 2.2% 6/45 13.3% 14/45 31.1% 19/45 42.2% Evidence of patient acceptability 2/45 4.4% 1/45 2.2% 16/45 35.6% 17/45 37.8% 9/45 20% Foreign guidelines 1/45 2.2% 3/45 6.7% 12/45 26.7% 20/45 44.4% 9/45 20% Cost information 1/45 2.2% 1/45 2.2% 9/45 20% 17/45 37.8% 17/45 37.8% National guidelines 0/45 0% 1/45 2.2% 2/45 4.4% 15/45 33.3% 27/45 60% Cost analysis 0/45 0% 3/45 8% 8/45 17.8% 17/45 37.8% 17/45 37.8%

Association between younger age and accurate knowledge of PrEP prescription Trending towards significance Newer general practitioners more likely to have increased knowledge No or slightly confidence prescribing PREP: 100% importance on national guidelines Age affecting concerns <55yo 53.8% concern with lack of guidelines >55yo 23.1% concern with lack of guidelines P=0.233

10 GPs were interviewed 15-20 minute individual interviews From Mackay region

Theme Positivity I think it s very exciting that you have a way to prevent the spread of HIV prevention is always better than a cure it makes sense from a population health point of view this is about patients, not about me It s not going to increase their promiscuity, you d just rather have them safe then not I don t think it will make them any more or less silly with risk taking behaviour

Men who have sex with men major underlying theme Prescription to sero-discordant couples minority

Theme Discomfort Uncomfortable to bring up PrEP with patients Would not want to bring it up with patients, but rather facilitate discussion after patient initiation Majority would prefer to refer to sexual health clinics

Lack of knowledge caused the most discomfort Able to identify PrEP was antiretroviral that was taken by patients at high risk a short course of antiviral treatment prior to I guess high risk sexual uh sexual intercourse with the idea being that you would sort of prevent HIV transmission

I m not someone that, wants to promote promiscuity it s not really something I really particularly want to encourage I m not going be advertising it. I certainly don t want my practice full of people that want it. I don t want those people in my practice

It wouldn t be a barrier to me talking and prescribing it to people, but for some people I can see it being a barrier to them filling my script. Guidelines Hard copies

GPs have limited knowledge of HIV PrEP Which is also their largest concern and barrier for prescription Discordance regarding societal appropriateness to prescribe PrEP GPs would like education to increase confidence Education sessions, hard copies and access to information