1. Adolescents and Adults Living with Perinatal HIV Cohort (AALPHI) Steering Committee Meeting 3 June 2013

2. Agenda 1.Welcome and introductions 2.Recruitment (Discussion) 3.Characteristic of cohort to date 4.Collaborations and funding 5.Sub-studies (Discussion) 6.AOB and date of next meeting

3. Recruitment

4. Inclusion criteria HIV-infected cases (PHIV+) n=400 13-21 years Previous paediatric HIV care In UK for >6 months Understand English Assent/consent HIV negative controls (HIV-) n=300 13-21 years HIV negative and aware of HIV in family/ household Living with case or sibling/ parent with HIV In UK for >6 months Understand English Assent/ consent

5. Participating clinics

6. Cumulative monthly recruitment (actual)

7. Cumulative monthly targets and actual recruitment

8. PHIV+ recruitment by clinic based on cumulative monthly targets

9. HIV- recruitment by clinic

10. How we have been improving recruitment since Jan Practical changes at sites following last SC: –Room all day at St Georges on 1 st and 2 nd Wed –Room at GOS –‘Recruitment facilitator’ at B&S Agreed with camp organisers and CHIVA exec for us to recruit at Camp in July Recruitment update e-mails Staffing changes ‘Recruitment Days’ & setting up Virtual Recruitment Group Widening HIV- eligibility

11. Recruitment update e-mails Every site to receive monthly up-date –First e-mail sent out at beginning of May. Included: Graph 1 Total recruited by all of the individual sites Graph 2 Cumulative accrual against targets Graph 3 Site specific information

12. Staffing changes Staffing changes: –Marthe’s maternity leave covered by Kate Sturgeon –Linda’s role currently being advertised Out of London research nurse (Katie Rowson) –Saves travel time –Access to potential new sites (Liverpool / Blue Sky Trust – Newcastle) –Katie has already established contacts

13. Staffing changes cont. In-house research nurses –At three main London sites –Allows more flexibility for interviews (where often high DNA rates) Implications of changes –Database changes (offline to web based) –Data quality and reliability –Pros and cons of using in-house CNSs as RNs –Training / handover

14. ‘Recruitment Days’ & setting up Virtual Recruitment Group Following SC discussion re: HIV- recruitment 2 pilot days –Positively UK (recruited 7 HIV-) –Faith in People (recruited 6 PHIV+ and 1 HIV-) Mixed half-days at PPC and B&S All during holidays or at weekend First e-mail sent to set up Virtual Recruitment Group –Organising teleconference to feedback on pilot days and to stimulate ideas and additional AALPHI days Further ‘AALPHI days’ –Currently 3 being planned for summer holidays –Excellent way of seeing large numbers in one day –Planned activates around day for YP

15. Widening HIV- eligibility Following discussions with other national cohorts at IWHOD, we will widen HIV- eligibility to include friends and partners We will monitor the characteristics of the group Aware may have small impact on science but believe benefits outweigh costs Additional data items to be collected: –If born outside UK, date came to UK –How they know the case and for how long –What city they live in

16. Other issues Two areas we will also be focusing on in next few months: –PHIV+ blood samples –PHIV+ casenote review PHIV+ blood samples: –not collected if seen in voluntary sector or not due bloods on day of interview –Need to catch up –RN will provide each clinic with a list

17. Other issues continued PHIV+ casenote review: Additional to CHIPS form Clinic staff need to: complete front page bring notes of PHIV+ already interviewed RN will send e-mail prior to visit with details of notes required

18. Discussion

19. Characteristics of cohort to date Based on 128 participants recruited up to 9 th May 2013

20. Ethnicity, sex and age (n=126/8) PHIV+HIV-Total Ethnicity, n (%) Black86 (83)16 (73)102 (81) Mixed12 (12)5 (23)17 (13) White3 (3)1 (5)4 (3) Other1 (1)0 (0)1 (1) Prefer not to say2 (2)0 (0)2 (2) Born abroad, n(%)64 (62)12 (55)76 (60) Sex, n (%) Male44 (42)6 (27)50 (39) Age Median (IQR) 17.0 (15.4, 18.8) 17.6 (15.1, 18.8) 17.2 (15.2, 18.8)

21. Marital status, children and current living situation (n=126) PHIV+HIV- Total Marital status, n (%) Single/never married103 (99)22 (100)125 (99) Co-habiting1 (1)0 (0)1 (1) Parent, n(%)1 (1)0 (0)1 (1) Lives with, n(%) Parents93 (89)19 (86)112 (89) Alone3 (3)1 (5)4 (3) Friends6 (6)2 (9)8 (6) Partner1 (1)0 (0)1 (1) Unknown2 (2)0 (0)2 (2) Parent died, n (%)39 (38)7 (32)46 (37)

22. Work/education status (n=115)

23. Drinking, smoking & drugs (n=125)

24. 45% of 11-15yr olds ever drunk alcohol * 5% of 11-15yr olds regular smokers * 38% of 16-24yr olds ever taken illegal drugs ** * Source: The Information Centre for Health and Social Care ** Source: Home Office

25. Sexual activity (n=124) PHIV+HIV- Total Ever had: Vaginal sex * 39 (38)8 (38)47 (38) Anal sex * 3 (3)2 (10)5 (4) Condom use (n=47) Always29 (74)3 (38)32 (68) Mostly5 (13)1 (13)6 (13) Sometimes3 (8)4 (50)7 (15) Never2 (5)0 (0)2 (4) * 6 participants chose not to answer these questions. Percentages are based on all 124 participants.

26. Sexual activity (n=124) PHIV+HIV- Total Ever had: Vaginal sex * 39 (38)8 (38)47 (38) Anal sex * 3 (3)2 (10)5 (4) Condom use (n=47) Always29 (74)3 (38)32 (68) Mostly5 (13)1 (13)6 (13) Sometimes3 (8)4 (50)7 (15) Never2 (5)0 (0)2 (4) * 6 participants chose not to answer these questions. Percentages are based on all 124 participants. ** Source: Office for National Statistics 88% men, 70% women aged 16-24 years used condoms in last 12 months **

27. Neurocognitive testing (n=123) PHIV+HIV- median (IQR) WAIS IV coding (raw score)52 (44, 60) 53.5 (42.5, 69.5) Pegboard dominant hand (time m:ss)1:09 (1:00, 1:20) 1:15 (0:58, 1:19) Pegboard non-dominant hand (time m:ss)1:20 (1:10, 1:31) 1:11 (1:03, 1:19) Colour trails 1 (time, m:ss)0:43 (0:34, 0:55) 0:37 (0:29, 0:53) Colour trails 2 (time, m:ss)1:22 (1:03, 1:40) 1:08 (0:53, 1:48)

28. Cogstate (n=108) ↑↓ better? PHIV+HIV- mean (sd) Norms* Detection (log 10 (time))↓2.5 (0.1) 2.4 (0.1) Identification (log 10 (time))↓2.7 (0.1) 2.6 (0.1) One card learning (arcsine(correct))↑0.9 (0.1) 0.9 (0.2) One back memory (arcsine(correct))↑1.3 (0.2) 1.2 (0.1) Groton maze learning (total errors)↓57.0 (25.2)52.7 (13.3)- Shopping list (correct)↑24.4 (4.1)26.6 (3.2)- Delayed shopping list (correct)↑8.6 (2.1)9.3 (1.7)- * Source: Cogstate normative data for 25-30 year olds

29. HADS anxiety score (n=120) GroupnMeanStd. Dev. PHIV+996.43.9 HIV-216.04.4

30. HADS depression score (n=120) GroupnMeanStd. Dev. PHIV+993.93.1 HIV-213.22.8

31. Counselling and self-harm (n=120) PHIV+HIV- Total Self-harmed (n=121) 16 (16)8 (38)24 (20) Thought about killing themselves (n=51) 26 (26)6 (29)32 (26) Referred to mental health service (n=120) 6 (6)3 (14)9 (8) Referred to psychology or counselling (n=120) 27 (27)6 (29)33 (28)

32. Counselling and self-harm (n=120) PHIV+HIV- Total Self-harmed (n=121) 16 (16)8 (38)24 (20) Thought about killing themselves (n=51) 26 (26)6 (29)32 (26) Referred to mental health service (n=120) 6 (6)3 (14)9 (8) Referred to psychology or counselling (n=120) 27 (27)6 (29)33 (28) 19% in ALSPAC * 16% in ALSPAC * * Source: ALSPAC 2012

33. Self worth (n=121) Agree/ Disagree PHIV+HIV- Person of worth on equal plane Strongly agree or agree with statement 92%100% Number of good qualities94%95% Able to do things as well as others92%90% Positive attitude towards themselves87%81% Satisfied with themselves81%71% Inclined to feel they are a failure Strongly disagree or disagree with statement 85%90% Do not have much to be proud of75%86% Wish had more respect for themselves58%71% Feel useless at times51%62% Think they are no good at all59%76%

34. Disclosure and ART (PHIV+) (n=102) n (%) Recall age of disclosure 80 (78) Age in years, median (IQR) 12 (10, 14) Currently taking ART 93 (90) Took all doses in last 3 days 68 (73)

35. Viral loads by ART status (n=69)

36. CD4 by ART status (n=67)

37. CDC stage by ART status (n=65)

38. Relationship to case (HIV-) (n=18)

39. Collaborations and funding

40. Presentations Characteristics and risk behaviours of perinatally HIV-infected and HIV-uninfected young people recruited into a new adolescent cohort, UK. 5 th International Workshop on HIV Pediatrics, Kuala Lumpur, 2013 (forthcoming). Recruiting HIV negative siblings into research studies of perinatally HIV-infected young people: experiences from the first 9 months of the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort, UK. CHIVA Spring Conference, Leeds, 2013. Prize for best poster. Sex, drugs and mental health characteristics of perinatally HIV-infected young people recruited into the new Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort, UK. 17 th IWHOD, Cavtat, 2013.

41. Authorship guidelines Named authorship: “Firstperson A, Secondperson B, Thirdperson C, etc…., on behalf of the Adolescents and Adults Living with Perinatal HIV (AALPHI) Steering Committee” Authorship based on uniform requirements Full acknowledgements lists of all participating sites + funders 10 day lead time for abstracts, talks, posters; 15 for papers Reviewed by AALPHI project team and circulated to SC for information (members may be invited to provide comments)

42. US PHACS AMP Growth & puberty; CVD; bone; neurologic, neurodevelopment; language, hearing; behavioural function; STIs 451 cases: 7-15 yrs, PHIV+ (median age 12) 228 controls: 7-15 yrs, PHEU (median age 10) Annual visits up to 18 years Re-consent all participants at age 18 years –Face-to-face interviews at 18 and 21 years –Web-based interviews at 19 and 20 years Several papers published and in press

43. French “Coverte” Transition to adulthood schooling, jobs, sexual and reproductive health morbidity and mortality, adverse events indicators of premature ageing (CVD, metabolic, immunology) 400 cases: 18-25 yrs, diagnosed <13 years 75 controls: 18-25 yrs, HIV- (sibling/ relative) Baseline and month 36 assessments

44. 18-25 y HIV diagnosis before the age of 13 N=400 expected +/- PHYSIOPATHOLOGICAL MODULE (J0 & M36) Self-administered Q (nutritional habits) OGTT CT-scan and DXA-scan Cardiovascular: IMT, pulse wave velocity COMMON MODULE Clinical examination Self-administered Q « living conditions & behaviour » Blood sampling Biobank ANRS CO19 Coverte Sample of 200 HIV+ Healthy adult controls 18-25 y HIV- (siblings and other relatives) N=75 expected J0 & M36 : Common module & physiopathological module

45. 18-25 y HIV diagnosis before the age of 13 N=400 expected +/- PHYSIOPATHOLOGICAL MODULE (J0 & M36) Self-administered Q (nutritional habits) OGTT CT-scan and DXA-scan Cardiovascular: IMT, pulse wave velocity COMMON MODULE Clinical examination Self-administered Q « living conditions & behaviour » Blood sampling Biobank ANRS CO19 Coverte Sample of 200 HIV+ Healthy adult controls 18-25 y HIV- (siblings and other relatives) N=75 expected J0 & M36 : Common module & physiopathological module Recruitment since June 2010: 234 HIV+ 5 HIV-

46. Timelines 2013 onwards 201320142015 JJASONDJFMAMJJASONDJFMAMJJASO 1 st year 2 nd year 3 rd year D’load Analysis MT ends Funding started September 2011 Year 1 interviews started July 2012

47. Planning for Year 2 Face-to-face Web-based software to facilitate downloading/ syncing from multiple sources Comprehensive review of data quality and initial findings Contact key experts to discuss year 2 content Review papers from PHACS

48. Retention Explore access to internet –Do you have a mobile phone? –Can you access the internet on it? –Do you normally have credit for your phone? –Do you have private internet access apart from on your phone? If so where? –Would you be happy to fill out Alfie questions without the research nurse: on your phone; on your computer where you have private access; in the HIV clinic/NGO?

49. Current funding Monument Trust –£200,000 per year for 3 years –Funding commenced in Sept 2011 so runs to Aug 2014 EuroCoord (EU FP7) –€10K per year for 5 years

50. Future funding ideas Key objectives of AALPHI: –Neurocognitive and psychosocial outcomes –Short-term and long-term morbidity Wellcome Trust Strategic Award or Fellowship –Immunology basic science – t cell repertoires –Cardiovascular markers – clinical PhD –Bone biochemistry – DEXAs and portable scanners NIHR Programme Grant for applied research –What are the problems/ what services needed/ what cost Co-funding from Monument Trust

51. Sub-studies

52. Substudies - current No new studies since previous SC meeting Cardiovascular (Julia Kenny) planned for yr 2 –Wellcome or BHIVA funding for PWV and biomarkers HPV vaccination uptake (Rachel Sacks) –Questions integrated into yr 1 and proceeding as planned Mixed methods adherence (Marthe) –MRC CTU funded PhD exploring factors affecting long-term adherence to ART in perinatally-infected young people

55. Funding – way forward Two potential strategies for The Monument Trust: 1: Intensify funding for 18 months following current end to allow us to apply for new funding once year 1 complete 2: Continue funding AALPHI core (neurocog/ psychosocial); team to seek additional funding now from 2+ sources for add on studies

56. US PHACS AMP – key findings Metabolic –15% PHIV+ had insulin resistance, associated with obesity –BMI & total body fat  in PHIV+ v HEU, but PHIV+ had  trunk to extremity fat ratio –TB & LS BMD z scores  in PHIV+ –Fracture incidence low and similar in PHIV+ v HEU

57. US PHACS AMP – key findings Growth –Pubertal onset 0.5-1 year later in PHIV+ and associated with high VL and low CD4, & was earlier with more ART Cardiac –Total & HDL chol & trig inflammation markers  in PHIV+ Mental health –Prevalence of mental health problems higher than national norms, and  in HEU- than PHIV+ –Cognitive and adaptive functioning  in PHIV+ with CDC C