hptn 067/adapt methods and results from women in cape town
TRANSCRIPT
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
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
HPTN 067 Design
Final Study Visit
Week 34
6 weeksDOT
period
24 weeks self-administered
dosing
4 weeks
off drug
FTC/TDF
Sex coverage Random
ized
D
T
E
Daily- One tablet/dayTime driven- 1 tablet/2x week with a post sex boostEvent 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
Silom Community Clinic178 HIV-uninfected at riskMSM/TGWBangkok, ThailandCompleted March 2014
Emavundleni Prevention Centre179 HIV-uninfected at risk WSMCape Town, South AfricaCompleted June 2013
Harlem Prevention Center179 HIV-uninfected at risk MSM/TGWNYC (Harlem), USA Completed Dec 2014
Bekker IAS2015, Vancouver, 2015
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
Definition: Covered sex eventCoverage 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
294screened
191enrolled
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%
60Daily usage
59Time-driven usage
60Event-driven usage
DOTPhase
Self-Administered Phase
Bekker IAS2015, Vancouver, 2015
• 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
Coverage of Sexual Intercourse:Cape Town
% completecoverage
% only pre-sex dose
% only post-sex dose
no coverage
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
75%
21%
1% 3%
56%
30%
9%6%
52%
33%
8% 7%
Daily
Time-driven
Event-driven
Sex event defined as vaginal or anal intercourseTime vs Daily p = 0.0006, Event vs. Daily p < 0.0001, Time vs Event p = 0.46
Bekker IAS2015, Vancouver, 2015
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)
Daily Time-driven Event-driven
9758
3629
2205
7441
28592002
Required tabletsTablets reported taken
Nu
mb
er
of t
ab
lets
Bekker IAS2015, Vancouver, 2015
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
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
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
TFV-DF in PBMCs: % with TFV-DP > 9.1 fmol/M PBMC*
Time period Study RegimenDaily (D)
Study RegimenTime (T)
Study RegimenEvent (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=0.63Bekker IAS2015, Vancouver, 2015
• 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
• 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
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 representLinda-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