State of the Sciences: Research Updates from the IAS Leadership Tuesday, December 8, 2015 Johns Hopkins Bloomberg School of Public Health

1. PrEP in adolescent girls
and young women:
Vulnerabilities and Opportunities.
Linda-Gail Bekker
The Desmond Tutu HIV Centre, UCT
International AIDS Society
Dec 2015

2. Antiretroviral therapy as Prevention

5. Who?

7. “Today’s
generation
of young
people is
the largest
in human
history”
UNFPA, 2013
©UNICEF/HQ00-0779/Donna Descare
10-24 year olds: ¼ of the
World’s population
10-24 year olds: ¼ of the
World’s population
1/3 of Africa’s population

9. Africa’s Youth Bulge….

10. Adolescent health –Lancet
• “Adolescence is a time in life that
harbours many risks and dangers, but
also one that presents great
opportunities for sustained health and
wellbeing through education and
preventive efforts.
• Never before was there such a
discrepancy between sexual and
psychosocial maturity.”
Sabine Kleinert, Lancet series.

11. An urgent and ongoing crisis:
2 500 infections every day : 1 new infection every 30 seconds
80% of new infections in SSA

12. New HIV Infections in Adolescents in 20
Countries with Highest Number of New HIV
Infections, 2012

13. HIV prevalence: 15-24 yr old
Young women Southern Africa
are 3-6x more likely HIV +
than males

14. Young and vulnerable
Age
Group
(Years)
KZN HIV
Prevalence
ANC
(N=1029)
CT HIV
Prevalence
General
Female
(N=600)
≤16 8.4% 12%
17-18 18.6% 17%
19-20 25.4% 30%
Incidence KZN (16-35 yo) : 9% and Cape Town (16-20) yo : 8%

15. Adolescence is a Developmental
Transition: Biological and behavioural
vulnerabilities
Pre-adolescence
10-13 years
Pre-adolescence
10-13 years
Middle Adolescence
14-16 years
Middle Adolescence
14-16 years
Late Adolescence
17-20 years
Late Adolescence
17-20 years
Emerging Adulthood
21-25 years
Emerging Adulthood
21-25 years

16. Adolescence is a Developmental
Transition: Biological and behavioural
vulnerabilities
Pre-adolescence
10-13 years
Pre-adolescence
10-13 years
Middle Adolescence
14-16 years
Middle Adolescence
14-16 years
Late Adolescence
17-20 years
Late Adolescence
17-20 years
Emerging Adulthood
21-25 years
Emerging Adulthood
21-25 years
• Greater Risk Taking
• Present Bias
• Poor knowledge and application of knowledge
• Lack of abstract thought
• Disregard for rules and establishment
• Poor health seeking behaviours
• Prejudicial and inadequate health services
• Lack of privacy

17. OK, at which point
exactly do I suggest
he puts on a condom
……or ask about HIV
status….. and
whether he is on
ART….. and whether
he is virally
suppressed????

18. For the first time
in my life, oral
Prep allows me to
own my sexuality
Sinazo Peters 22 yrs,
Former “Future Fighter”
Desmond Tutu HIV Foundation

19. HIV infections averted per
100 person years of PrEP
0.0
0.5
1.0
1.5
2.0
2.5
3.0
15-19 20-24 25-34 35-49 50+
Age group in which PrEP is provided
Female
PrEP
Male
PrEP
Johnson L, 2014

21. Frontal lobe re-modeling until 25 yrs
Blakemore S-J, http://brainposts.blogspot.com/2012/09/the-adolescent-brain-ted-talk-
by.html

22. Diffusion of Innovation favours :
• Still adapting and developing frontal lobe
– Executive function still developing
– Impulse control inadequate
– Long term decision making poor
• Better developed limbic lobe
– Emotional
– Impulsive
– Short term gratification
Science Illustrated Boness L,

23. Roger’s theory of dissemination
Beaudoin P et al. 2014
Adolescents are Early AdoptersAdolescents are Early Adopters
Girls >
boys
BOYS>
GIRLS
GIRLS>
BOYS

24. Annual number of voluntary medical
male circumcisions, 2009–2012
24
Number of male
circumcisions
UNAIDS Global Report 2013
1 800 000
1 600 000
1 400 000
1 200 000
1 000 000
800 000
600 000
400 000
200 000
0
2009 2012
2/3 of MSM
volunteering for
SIBANYE PrEP
demo in CT are 18-24 years

25. To get to 50 million people….
• Radio : 38 years
• Phone: 20 years
• TV: 13 years
• Facebook : 3.6 yrs
• Twitter: 1.5 yrs
• Google plus: 88
days

26. Cashing in on evolving
capacities
“Invention is the talent of youth, as judgement is of age”
Jonathan Swift

27. At the end of 2013, there were 1.2
billion Facebook users in the world
and 82% of them were between the
ages 18 and 35 years.
The Associated Press. Number of active users at Facebook over the years: How Facebook has grown:

28. At the end of 2013, there were 1.2
billion Facebook users in the world
and 82% of them were between the
ages 18 and 35 years.
The Associated Press. Number of active users at Facebook over the years: How Facebook has grown:

29. • 222 participants (69,4% female) between the
ages of 16 – 25 yrs.
• Conclusion:
– HIV self-testing device can be used accurately and
is acceptable to a young population.
– Participants reported high usability and
acceptability ratings, with younger participants and
new testers giving higher acceptability scores.
Atomo rapid HIV
testing device

30. Accessible
Efficient
Friendly
Tailored
Funky
Comprehensive
One STOP Shopping
Contraception
HIV, STI, Preg screening
Mental health screens
Basic primary care
CD4, VL
ART, BMI, Blood sugar
CV writing, ID books
Hairbraiding,
manicures
Music
WIFI
Contraception
HIV, STI, Preg screening
Mental health screens
Basic primary care
CD4, VL
ART, BMI, Blood sugar
CV writing, ID books
Hairbraiding,
manicures
Music
WIFI
Philip, Elzette

31. Youth messaging….Youth messaging….
Youth marketing….Youth marketing….

32. Studies in the field
(Specifically targeting adolescents)
• MTN 023 : Dapivirine Gel : 16-17yo (96) USA
Safety, acceptability F
• ATN 113: TDF/FTC PrEP: 15-17yo (79) USA
Safety, acceptability, adherence. 79 MSM
• ATN 110: TDF/FTC PrEP: 18-24 yo (200)
• Kenyan MP3 : TDF/FTC PrEP: 15-24 yo (40) F
Kenya 1 Site. Safety, feasibility, adherence
• CHAMPS-Pluspills : TDF/FTC PrEP : 15-19 yo
M+F. Safety, adherence, use. 2 sites (150)

33. ADHERENCE EFFICACY
Partners PrEP
BK IDU
TDF2
iPrEx
CAPRISA 004
FEMPREP
VOICE
AGE
<25 years
>25 years
If we offer it- will they take it “well
enough”
RCTs of
pre-
exposure
prophylaxis
with antiviral
agents in
HIV
negative
RCTs of
pre-
exposure
prophylaxis
with antiviral
agents in
HIV
negative

35. SO WE DEFINETLY KEEP TRYING TO
GET CONTRACEPTION RIGHT….

36. ADAPT/HPTN 067 in Cape
Town
A comparison of daily and nondaily PrEP
dosing in African women.

37. Overall Purpose:
A Behavioral study to evaluate the
feasibility of non daily PrEP regimens.
Recommendations for intermittent usage,
compared with daily usage, to provide
comparable coverage of risk exposures
with pre- and post-exposure dosing,
decreased pill requirements, and
decreased symptoms.

38. Overall PI: Robert Grant
Silom Community Clinic
178 HIV-uninfected at
risk
MSM/TGW
Bangkok, Thailand
March 2014
Emavundleni Prevention
Centre
179 HIV-uninfected at risk
WSM
Cape Town, South Africa
June 2013
Harlem Prevention
Centre
179 HIV-uninfected at
risk
MSM/TGW
NYC (Harlem), USA
Dec 2014

39. CRS leader: Surita Roux
Study Coordinator: Elaine Sebastian
CLO: Ntando Yola

40. Cross Roads: 500 000

41. Final
Study
Visit
Randomized
D
T
E
HPTN 067 Design
Screening
Enrollment
TDF/FTC
1 dose Weekly
for 4 weeks
PK steady
State
Sex coverage
Daily- Once daily dosing
Time driven- 2 doses/week with post coital boost
Event driven- pre and post coital dosing
No more than 1 dose daily and 7 doses/week
Wk 0 Wk 34
191
Qualitative :
Staff
60 Participants
IDIs and FGs

42. Methods
• Coverage for all arms was defined as >1 pill
taken in the 4 days before and >1 pill taken in
the 24 hours after sexual intercourse
• Adherence was defined as the percentage of
recommended pills taken for each regimen
• Plasma and PBMC were collected and
analyzed for tenofovir (TFV) and
Emtracitabine (FTC) and their active
metabolites at 10 and 30 weeks

43. Sexual Coverage and
Adherence
• Pills were dispensed from
an electronic dispensing
Wisepill device that
recorded each opening.
• Weekly wisepill reports sent
to site for each participant.
• Participants were contacted
weekly by phone or in
person to review Wisepill
data and sex events.

44. Median age 26 (18-52) ; 80% Unmarried; 83% unemployed
Baseline Characteristics

45. Side effects were uncommon
Side effects

46. Plasma TFV (consistent with >1 pill in prior week) and PBMC
TFV diphosphate (consistent with >2 pills in prior week) were
detected in more women in D compared with T and E.
Plasma and PBMC drug levels

47. Conclusions
• The majority of women in this study took oral
PrEP when made available in an open label study.
• Daily dosing resulted in better coverage of sex
acts and adherence, and higher drug levels.
• Daily dosing may foster better habit formation
and provide the most forgiveness for missed
doses at observed adherence levels.
• These findings support current
recommendations for daily use of oral FTC/TDF
PrEP in women.

48. Adherence and Risk Ratios

49. “PrEP Champions….”
RIP: Aphiwe
Naphakade 2014

50. Results Dissemination:
Cape Town 2015…..
• "PrEP should be easily accessible for
teenagers be it over the counter in clinics and
schools and should be for free".
• "Women should stand up and demand PrEP"
• "Participant should be ambassadors to
encourage community".
• "There should be mass campaigns, go back to
'Imbizo' and talk about these issues".
• "For us young women HIV prevention is
negotiating- and for men it is a choice, so
PrEP will help us".

51. : Cape Town

52. Youth in ADAPT

53. ADAPT
Number with detectable plasma
levels
Weeks on study Age (yrs) Daily arm
10 <25 87.0
30 <25 81.3
10 >25 100
30 >25 76.9
>40 ng/ml in plasma means a tablet was taken in last 24 hours
22% 18-20yrs ; 27 % 21-25yrs

54. African 13
USA : 8
Other: 9
Women: 5
Discordant couples: 2
MSM: 13
Sex Workers: 6
Men: 2
Youth All pops <18 : 5
Youth Women <18 : 3
African 13
USA : 8
Other: 9
Women: 5
Discordant couples: 2
MSM: 13
Sex Workers: 6
Men: 2
Youth All pops <18 : 5
Youth Women <18 : 3

55. Pluspills Study
• A Demonstration Open Label Study to
Assess the Acceptability, Safety and Use
of Truvada Pre-exposure Prophylaxis in
Healthy, HIV-Uninfected Adolescents, 15-
19 Years of Age.
• (under IND)

56. The DTHF Youth Centre, Kommetjie

57. PrEP : ready, steady, GO!
AS LONG AS YOU TAKE A PILL A DAY- THE VIRUS WILL STAY AWAY!!!

58. 150 Healthy 15-19yo, Sexually active
40:60 M:F Masiphumelele and Soweto
150 Healthy 15-19yo, Sexually active
40:60 M:F Masiphumelele and Soweto
Screen, enroll. Package +
PrEP
Screen, enroll. Package +
PrEP
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
CHOICE : package +/-PrEP
Acceptability
Reasons for choice
DBS + real time FB vs
none
0 Mo
3 Mo
6 Mo
9 Mo
Basic
Package:
HCT, MMC,
PEP,
condoms
Female
condoms
Basic
Package:
HCT, MMC,
PEP,
condoms
Female
condoms
12 Mo
Screen, enroll. Package +
PrEP
Screen, enroll. Package +
PrEP
Screen, enroll. Package +
PrEP
Screen, enroll. Package +
PrEP
2 Mo
1 Mo
DBS + real time FB vs
none
DBS + real time FB vs
none
DBS + real time FB vs
none
DBS + real time FB vs
none
Final VisitFinal Visit
DBS + real time FB vs
none
Choice of
daily,
weekly or
no SMSs
Choice of
daily,
weekly or
no SMSs
Adherence
clubs/Buddi
es
Adherence
clubs/Buddi
es

59. Drug detection levels
1/3 enrolled 25 M and 59 F1/3 enrolled 25 M and 59 F

60. Risk group
Soweto : 16 ( 2F; 14 M) enrolled
Cape Town: 48 (36F; 12 M) enrolled
Parental consent in <18 yo
No safety issues
Screening STI rates in AG

61. Sub-Studies: EASE
• Home testing- feasibility/accuracy
complete
• “Risk rater”- prototype being validated
• Dried Blood Spot + Plasma (real time)
• SMS messaging to enhance adherence
• Virtual adherence clubs using SMS texting
platform- “Khulumi”

62. 3 Ps for Prevention : Partners,
PrEP and Payment.
Formative
work on risk,
partners,
narratives
Formative
work on risk,
partners,
narratives
Behaviour
centred
ethnographic
work
Behaviour
centred
ethnographic
work
PrEP + SOP+CCTPrEP + SOP+CCT
PrEP + SOPPrEP + SOP
Best
message
Approach 1000
selected women
16-26 years
Approach 1000
selected women
16-26 years
Enrol,randomise
100 women
to PrEP +/- CCT
Enrol,randomise
100 women
to PrEP +/- CCT
CCT contingent on
Adequate drug levels monthly
For first 3 months.
CCT contingent on
Adequate drug levels monthly
For first 3 months.
12 months follow up
Generalcommunityof20000

63. HPTN 082
• To assess the proportion and
characteristics of young HIV-uninfected
women who accept versus decline PrEP
at enrollment.
– In the randomized cohort, to compare the
proportion of young women who are adherent
(by drug levels) to PrEP at Weeks 13 and 26,
in the enhanced versus standard arms.

64. Target Enrollment
• Uninfected women, 16-25,
southern Africa
• 400 women who accept
PrEP at enrollment
• Up to 200 women who
decline PrEP at enrollment
Follow-up duration: 12
months
Evaluation of daily oral PrEP as a
primary prevention strategy for
young African women:
A Vanguard Study
HPTN 082
PrEP = Daily oral
FTC/TDF
Enroll
Decline
Accept
Provide PrEP,
adherence
support, SOC
(400 women)
SOC and offer
PrEP
(up to 200
women)
Primary objective: Assess PrEP initiation, adherence, acceptability,
and continuation
among young women in three sites in southern Africa offered open
label oral PrEP.
Cellum C

65. HPTN 082
Decline
Accept
N = 400
Provide PrEP,
adherence
support, SOC
SOC and offer
PrEP
In-depth interviews exploring barriers/facilitators to PrEP initiation &
adherence in a subset of participants
Assess drug levels: Weeks 4, 8: provide results to participants at
next visit (Weeks 8 & 13) Weeks 13, 26 and 52:
retrospective analysis
When ~ 50% of participants who initiate PrEP at enrollment reach Week 13,
an interim assessment of drug levels from the 13 week visit will be performed.
If < 60% of the participants have detectable TFV at Week 13, follow-up will
end early at that site (at the next study visit or after Week 26)
Enroll
Daily oral
FTC/TDF
PrEP
N = up to 200

66. Dreams : Bridge to scale up!
• DREAMS is a partnership to reduce HIV
infections among adolescent girls and young
women in 10 sub-Saharan African countries.
• The goal of DREAMS is to help girls develop into
Determined, Resilient, Empowered, AIDS-free,
Mentored, and Safe women.
• Kenya, Lesotho, Malawi, Mozambique, South
Africa, Swaziland, Tanzania, Uganda, Zambia,
and Zimbabwe.
• 4-5 of 10 have included PrEP in their country
plan. PEPFAR, BMGF, NIKE

69. Issues and conjectures Responses and facts
Voice/ FemPrEP show PrEP won’t
work in African women
Voice/FEMPrEP show that women didn’t use a
study product in a placebo controlled trial
Oral PrEP isnt effective in women Daily oral PrEP prevents HIV acquisition among
women when taken with sufficient adherence.
Exposure in PP was low In a subset of PP with high exposure- PE exactly
the same as overall
STDs were lower in PP In subset of PP with STDs, efficacy is exactly the
same as overall
Surreptitious use of ART in PP Surreptitious use of ART would be balanced
across the arms = no bias.
Women shared PrEP in PP This would create real bias- PP checked for this
and none found.
PK data suggests PrEP wont work
in women
PK data suggest adherence has to be good, that’s
not the same as may not work. The PK/PD in vitro
data and the monkey data were very supportive of
PrEP.
VOICE/FEMPrEP show PrEP wont
work in clade C areas
Truvada works as well in clade C HIV +
We must wait for other options Demonstration and open label studies show that
women will step up and adhere with infection
saving outcomes.

70. Research Gaps: Oral PrEP
• What will motivate Pill uptake ?
• Barriers and facilitators to persistence?
• What can help adherence?
• Dosing? Forgiveness?
• When to stop? How to restart?
• Testing frequency and self testing
• How to monitor?
• Safety issues?

71. Youth at the centre of multiple epidemics
They can’t afford to wait -and neither can we….
in all scenarios and groups.

72. Conclusions
• YKP globally and YWAG in SSA are extraordinarily at risk for
HIV
• An unprecedented youth BULGE is occurring in Africa
exacerbating urgency.
• HIV treatment outcomes for youth are poor leading to
unacceptable morbidity and mortality
• Our options for HIV interventions are limited.
• Oral PrEP is a recent user dependent intervention to add to tool
kits
• Tailored, adolescent friendly, acceptable and feasible
prevention packages for YKPs and YWAG are URGENTLY
needed and SHOULD be tested in this population.
• We should consider ALL new interventions for their potential
to make a dent in the adolescent epidemic.

73. Follow us on face book:
http://www.facebook.com/home.php#!/pages/
The-Desmond-Tutu-HIV-Foundation-Youth-Centre/

74. Coming your way…. See Dazon Dixon Diallo

75. Thanks
Robin Wood and the DTHF/DTHC Family
HPTN and HVTN support over many years
Connie and Jared
Kai Jones
IDM: Val Mizrahi and team
DTHF PLUSPILLS TEAM–
Katherine Gill, Thola Bennie, Cleo Jaars, Francis Kayamba and whole team
PHRU Adolescent Division: Glenda, Janan Diedrichs, Fatima Laher, Sabelo
Mobile services: Philip Smith,Tutu Teen Truck and Tester Teams
Drs. Jo-ann Passmore, Heather Jaspan, Shaun Barnabas
(Wish studies. )
Dr. Leigh Johnson, School of Public Health, UCT
HAVEG: Cathy Slack and Ann Strode
DTHF Youth Centre and DTF YC Staff: Dante Robbertze, Jen, staff and Youth interns
Future Fighters (Youth CAB, DTHF)
Unicef Technical Reports: Craig McClure, Dr. Susan Kasedde (UNICEF)
CAPRISA- Slim and Quarraisha Karim
WHRI- Sinead and Helen.
ATOMO – Byron Darroch
Funders: NIH (MP3 network), ViiV Healthcare, IAVI, CDC, HVTN, PAWC, EDCTP, Chevron, UKAID, BMGF
Rotary, HVTN, HPTN, ALERE,
Adolescents and their Families