hptn 067/adapt methods and results from women in cape town

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


Primary:• Coverage of sex events • Number of tablets (required and

taken)• Self-reported side effects

Secondary:• Adherence• Safety• Acceptability• HIV infections

Outcomes


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


Review of results from Cape Town


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


• 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


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


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


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


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


Self-reported Neurological side effects by arm during follow-up


Self-reported GI side effects by arm during follow-up


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


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)


hptn 067/adapt methods and results from women in cape town

Healthcare