Grant R. и др. «HPTN 067/ADAPT methods and results from women in Cape Town» 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, 2015. MOSY0103.

1. HPTN 067/ADAPT
Background and Methods
and Cape Town Results:
Linda-Gail Bekker; James Hughes;
Rivet Amico; Surita Roux; Craig
Hendrix; Peter L. Anderson; Bonnie J.
Dye; Vanessa Elharrar; Michael J.
Stirratt; Robert M. Grant
Bekker et al, Poster 978LB, CROI Seattle 2015

2. Background
• Oral FTC/TDF PrEP is effective for preventing HIV acquisition.1
– Protection after rectal exposure is estimated to be:
• Near 100% with use of 4+ tabs/week.2
• 84% with use of 2 to 3 tabs/week,2
– Full protection after vaginal exposure requires more PrEP use.3
• Sex is often planned, and plans change over time.4
– PrEP provides benefit when used during seasons of risk.
– Such strategic PrEP use has been observed in MSM.2
– Measurement of adherence is challenging, especially when dynamic.5
• Recommending PrEP dosing before and after sex leads to effective use
among MSM taking on average 16 tablets per month.7
• Adapting PrEP regimens to match patterns of sex could increase strategic
PrEP use and minimize medication costs and side effects.
1. Grant NEJM 2010, Baeten NEJM 2012, Thigpen NEJM 2012, Choopanya Lancet 2013;
2. Grant Lancet Infec. Dis. 2014; 3. Cottrell (with Kashuba) R4P Cape Town, 2014;
4. van Griensven JIAS 2010; 5. Mutua PLoS One 2012, Kibengo PLoS One 2013;
6. Molina CROI Seattle 2015. Bekker IAS2015, Vancouver, 2015

3. HPTN 067 Design
Final
Study
Visit
Week 34
FTC/TDF
Sex coverage
RandomizedD
T
E
Daily- One tablet/day
Time driven- 1 tablet/2x week with a post sex boost
Event driven- 1 tablet pre-sex and 1 tablet post-sex
No more than 2 tablets daily or 7 tablets/week
Women
(incl. TGW)
& MSM
Key
informant
interviews
and focus
groups
Bekker IAS2015, Vancouver, 2015

4. Silom Community Clinic
178 HIV-uninfected at risk
MSM/TGW
Bangkok, Thailand
Completed March 2014
Emavundleni Prevention Centre
179 HIV-uninfected at risk WSM
Cape Town, South Africa
Completed June 2013
Harlem Prevention Center
179 HIV-uninfected at risk
MSM/TGW
NYC (Harlem), USA
Completed Dec 2014
Bekker IAS2015, Vancouver, 2015

5. Primary:
• Coverage of sex events
• Number of tablets (required and taken)
• Self-reported side effects
Secondary:
• Adherence
• Safety
• Acceptability
• HIV infections
Outcomes
Bekker IAS2015, Vancouver, 2015

6. Definition: Covered sex event
Coverage for all arms:
>1 pill taken in the 4 days before sex
>1 pill taken in the 24 hours after sex
>1 tablet >1 tablet
Bekker IAS2015, Vancouver, 2015

7. Review of results
from Cape Town
Bekker IAS2015, Vancouver, 2015

8. 294
screened
191
enrolled
103 not enrolled*
HIV + rapid 7/ 6.8%
Pregnant 3/ 2.9%
Lab abnormality 3/ 2.9%
Not Hep B immune 29/ 28.2%
Other medical/mental 12/ 11.7%
Low HIV risk 26/ 25.2%
Withdrew consent 1/ 1%
Not enrolled in window 14/ 13.6%
Other 10/ 9.7%
179
randomized
12 not randomized
HIV + rapid 2/ 16.7%
Relocated 3/ 25%
Pregnant 1/ 8.3%
Lost contact 2/ 16.7%
Other 4/ 33.3%
60
Daily
usage
59
Time-
driven
usage
60
Event-
driven
usage
DOT
Phase
Self-Administered Phase
Bekker IAS2015, Vancouver, 2015

9. • 100% Women
• Mostly young
– Age median 26
– Age range 18-52
• 80% never married
• 83% unemployed
• 99% black
• Residing in or near
Crossroads area of Cape
Town
Baseline Characteristics
Bekker IAS2015, Vancouver, 2015

10. Coverage of Sexual Intercourse:
Cape Town
75%
21%
1% 3%
56%
30%
9%
6%
52%
33%
8% 7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
% complete
coverage
% only
pre-sex dose
% only
post-sex dose
no
coverage
Daily
Time-driven
Event-driven
Sex event defined as vaginal or anal intercourse
Time vs Daily p = 0.0006, Event vs. Daily p < 0.0001, Time vs Event p = 0.46
Bekker IAS2015, Vancouver, 2015

11. FTC/TDF Tablets Required and
Tablets Taken by Arm
Required tablets: p<0.0001 for all comparisons (D/T, D/E, and T/E)
Tablets actually taken: p<0.0001 for all comparisons (D/T, D/E, and T/E)
9758
3629
2205
7441
2859
2002
Daily Time-driven Event-driven
Numberoftablets
Required tablets
Tablets reported taken
Bekker IAS2015, Vancouver, 2015

12. Adherence to the Prescribed Regimen:
Cape Town
Time vs. Daily p = 0.002, Event vs. Daily p < 0.0001, Time vs. Event p < 0.0001.
Bekker IAS2015, Vancouver, 2015

13. HIV Incidence Outcomes
• 2 seroconversions during 6-week pre-randomization weekly DOT
study phase one tablet one time per week.
– Occurred at weeks 4 and 5.
– Incidence 8.9 / 100PY (2 / 22.6)
– No detectable drug in plasma at visits preceding seroconversion
for either participant.
• 5 seroconversions during 24-week self administered PrEP phase
– 2 in Time-Driven, 2 in Event-Driven, 1 in Daily
– Incidence 5.4 / 100PY (5 / 92.3)
– 3 had negligible drug levels at or before seroconversion
• 2 had detectable but low drug levels
Bekker IAS2015, Vancouver, 2015

14. Neuro and GI symptoms /
side effects
Side Effect reported Daily Time Event p-value
% PPTs who experienced
any Neurologic side effect 47% 14% 19% 0.07
% PPTs who experienced
any GI side effect 38% 31% 20% 0.08
Bekker IAS2015, Vancouver, 2015

15. Self-reported Neurological side
effects by arm during follow-up
Bekker IAS2015, Vancouver, 2015

16. Self-reported GI side effects by
arm during follow-up
Bekker IAS2015, Vancouver, 2015

17. TFV-DF in PBMCs:
% with TFV-DP > 9.1 fmol/M PBMC*
Time period Study
Regimen
Daily (D)
Study
Regimen
Time (T)
Study
Regimen
Event (E)
Week 10
(with sex in the past 7 days)
81%
(33/41)
52%
(12/23)
54%
(20/37)
Week 30
(with sex in the past 7 days)
66%
(19/29)
46%
(11/24)
32%
(10/31)
*Indicative of at least 2 tablets per week.
Time vs Daily p = 0.01, Event vs Daily p = 0.002, Time vs Event p=0.63
Bekker IAS2015, Vancouver, 2015

18. • Thresholds of adherence and drug concentrations required
for full protection after vaginal exposure are not yet known.
• Recent PK/PD modeling suggests that full protection from
vaginal exposure to HIV requires daily or near daily use.1
• The ADAPT trial participants were informed that daily oral
PrEP was effective but that non-daily dosing was unproven.
– Could have undermined adherence in the non-daily arms.
– Belief in efficacy is a strong facilitator of adherence.2
• Weekly telephone contact may have served as reminders.
Limitations
1. Cottrell OA22.06. R4P Cape Town 2014;
2. Chemnasiri WELBPE23 IAS Vancouver 2015. Bekker IAS2015, Vancouver, 2015

19. • The majority of young, predominately single, South African
women took oral PrEP when made available in an open label
study.
• Recommending daily dosing resulted in higher coverage of
sex events, higher drug concentrations, and higher
adherence.
• Daily dosing fosters habit formation, provides the most
forgiveness for occasional missed doses and does not require
planning for sex.
• These findings, and PK findings from vaginal tissues, support
current recommendations for daily use of oral FTC/TDF PrEP
in women.
Conclusions
Bekker IAS2015, Vancouver, 2015

20. The HIV Prevention Trials Network is sponsored by the
National Institute of Allergy and Infectious Diseases,
the National Institute of Mental Health, and the National
Institute on Drug Abuse, all components of the
U.S. National Institutes of Health.
ACKNOWLEDGEMENTS
The HPTN 067 Cape Town Study Team acknowledges key support and
contributions of the following:
HPTN 067 Participants and the African women they represent
Linda-Gail Bekker, Surita Ruoux, Elaine Sebastian and the Ema staff and CAB
HPTN 067 Protocol Team (including those at LC, LOC, SDMC and DAIDS)
Bekker IAS2015, Vancouver, 2015