Transcript The Evidence * PrEP Effectiveness

The Evidence –
PrEP Effectiveness
Module 1(b)
The Evidence in Detail
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Session Overview
• Seroconversion rates
• PrEP Studies: MSM, transgender population, women, discordant
couples
• Benefits of PrEP
• Barriers to PrEP services
• Barriers and quality of care
• Bone mass density
• ART, universal test and treat
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Seroconversion rates in clinical studies of
TDF/FTC for PrEP
HIV-1 seroconversion rates for participants on TDF/FTC for PrEP are variable in
clinical studies (0.5 to 4.7 per 100 person-years exposure)
MSM
MSM,
TGW
Discord
Hetero
Couples
Hetero
Men &
Women
Women
Women
France Canada
UK
S. America
Africa
USA
Africa
Botswana
Africa
Africa
IPERGAY
PROUD
IPREX
Partner’s
PrEP*
TDF2
FemPrEP
MTN003/
VOICE*
Seroconversion rate/
100 person-years
MSM
*TDF/FTC only.
Transgender women
(TGW)
® (TDF/FTC)
Mera, R. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Characteristics of seroconverters in
demonstration projects
Seroconversion Rates By Sex/Gender
* Includes genderqueer,
androgynous
designations.
Total exposure, p-y
Number of HIV-1
seroconversions
Rate/100 p-y
(95% CI)
Men
n=7002
Women
n=1388
Transgender
Women*
n=76
6214
788
48
64
2
1
1.03
(0.80-1.32)
0.25
(0.03-0.92)
2.07
(0.05-11.52)
TDF/FTC
Mera, R. AIDS 2016
McCallister, ASM Microbe 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Seroconversion rates in demonstration
projects (July 2012 to May 2016)
Seroconversion Rates
From 32 Projects
32 individual studies of TDF/FTC for PrEP
• 8,478 participants


>1.5/
100 p-y
6 projects
0.1–1.5/
100 p-y
9 projects

7,002 men
1,388 women
76 transgender
• 7,061 cumulative person-years of TDF/FTC exposure
0/100 p-y
17 projects
Results
• 67 HIV-1 seroconversions
• 0.95/100 p-y seroconversion rate
(95% CI: 0.74, 1.21)
Mera, R. AIDS 2016
McCallister, ASM Microbe 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
5
MSM
PrEP and MSM
Pragmatic Open-Label Randomised Trial of PrEP (UK)
High-risk, HIV-uninfected MSM
engaging in CAI*
N=545
Immediate (IMM) TVD
(n=276)
Deferred (DEF) TVD
(start at Month 12)
(n=269)
Primary endpoint:
HIV seroconversion between
randomisation and Month 12
Secondary endpoints:
Safety, adherence, sexual behaviour,
resistance development
Oct 2014: the PROUD Trial Steering Committee announced that participants on the deferred
arm of the study, who had not yet started PrEP, would be offered the opportunity to begin
PrEP ahead of schedule
* CAI: Condomless anal intercourse
All subjects received comprehensive HIV prevention services, including condoms, risk-reduction counseling, testing and treatment for
sexually transmitted infections, and HIV pre- and post-test counseling
McCormack S, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
MSM
HIV incidence
Group
Infections, n
Follow-up (PY)
Incidence/100 person-years
(90% CI)
Overall
22
453
4.9 (3.4-6.8)
Immediate
3
239
1.3 (0.4-3.0)
Deferred
19
214
8.9 (6.0-12.7)
Use of post-exposure prophylaxis by arm:
• IMM: 13 subjects (5%); 15 prescriptions
• DEF: 83 subjects (31%); 174 prescriptions
86% (90% CI: 58%-96%) Risk Reduction; P=0.0002
Number needed to treat=13 (90% CI: 9-25)
McCormack S, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
MSM
Reported sexual risk behaviour and incidence of
sexually transmitted infections
Anal sex partners in past 90
days, median (IQR)
Baseline, n=539
Month 12, n=349
IMM
DEF
IMM
DEF
10.5 (5-20)
10 (4-20)
10 (3-24)
8 (3-15)
Condomless receptive
3 (1-5)
2 (1-5)
3 (1-8)
2 (1-5)
Condomless insertive
2.5 (1-6)
3 (1-7)
3 (1-8)
3 (1-6)
Immediate
Deferred
Total
70
60
50
40
30
20
10
0
P=0.08
P=0.44
P=0.44
P=0.08
No
significant
differences in
STIs between
the deferred
and
immediate
arms
P=0.32
Any STI
Gonorrhoea Chlamydia
Syphilis
Rectal
GC/CT
McCormack S, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Younger
MSM
Adolescents
Safety and efficacy of TDF/FTC for PrEP in US
MSM aged 15-17
ATN 113: PrEP
Demonstration
Project and Safety
Study
*TDF/FTC is not FDA approved for use in those <18 years old
Open-label, multi-site US demonstration project of
TDF/FTC for PrEP in 15-17 yo MSM, n=79
Adherence:
TFV-DP (fmol/punch) via DBS w/ Dosing Estimates
100%
90%
80%
60
52
55
32
23
28
70%
50%
350-699
(2-3 days)
BLQ
40%
30%
•
•
>700 (4 or
more days)
<350
(2 days)
60%
• Sharp drop in adherence when transitioning
from monthly to quarterly follow-up
•
Compared with adherent participants, nonadherent participants tended to be more likely to
endorse the beliefs:
•
20%
10%
•
0%
Wk 4
Wk 8
Wk12
Wk 24
Wk36
95% had detectable drug when monitoring was monthly
Unlike ATN 110 (18-22 yo), drop in adherence was
consistent across all races/ethnicities
Wk48
•
“I worry others will see me taking pills and think I am HIVpositive” (p=0.03)
“I am concerned people will know I have sex with other men
because I’m taking PrEP” (p=0.06)
“I don’t like taking pills” (p=0.06)
Hosek S, et al. AIDS 2016.
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Safety and efficacy of TDF/FTC for PrEP in US
MSM aged 15-17
ATN 113: PrEP
Demonstration
Project and Safety
Study
Younger
MSM
Adolescents
*TDF/FTC is not FDA approved for use in those <18 years old
Open-label, multi-site US demonstration project of
TDF/FTC for PrEP in 15-17 yo MSM, n=79
TFV Levels in Seroconverters
Pt 1 (wk 32)
Pt 2 (wk 36)
Pt 3 (wk 48)
TFV-DP Level
1200
1000
800
600
4+ doses
Three seroconversions occurred in
3 separate adolescents with no
detectable TFV
• HIV incidence = 6.41/100py (95%
CI: 4.9-25.8)
400
200
0
Wk 4
Wk 8 Wk 12 Wk 24 Wk 36 Wk 48
Hosek S, et al. AIDS 2016.
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
ATN 113: PrEP
Demonstration
Project and Safety
Study
Younger
MSM
Adolescents
Safety and efficacy of TDF/FTC for PrEP in US
MSM aged 15-17
STI Diagnosis
9
Safety:
• No d/c due to side effects
• Three Grade 3 AEs (weight loss) in 2 participants
deemed related to study drug by investigator
• No abnormal laboratory results
15.4% of participants had STIs on screening
8
7
6
5
4
3
2
1
0
Rectal Gonorrhea
• STI incidence decreased while on TDF/FTC for PrEP
Participants liked the engagement aspects of the
study more than the medication aspects
TDF/FTC for PrEP was well tolerated in these younger MSM and
adherence may be improved by addressing barriers of frequent
monitoring and stigma
Rectal Chlamydia
Baseline
Week 24
Syphilis
Week 48
Acceptability: Participants Liked/Liked A Lot
100
90
80
70
60
50
40
30
20
10
0
Pill Size
Pill Taste
Daily Pill
HIV tests
Counseling
Study
Week 12
Week 48
Hosek S, et al. AIDS 2016.
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
ATN 110 Study
Extension Phase
(EPH)
BMD changes in 18-24 year old MSM after
discontinuing TDF/FTC PrEP
Bone Mass
Density
Extension Phase
• DXA scans at 48 weeks after discontinuing PrEP study, i.e. 48 weeks on TDF/FTC followed by 48 weeks off
TDF/FTC
• N=72 individuals followed-up through the EPH
BMD change (mean)
Hip
Whole Body
Lumbar Spine 1-4
From BL to Wk 48
(on TDF/FTC)
From Wk 48 to end of
EPH
(off TDF/FTC)
Overall change from BL
to end of EPH
-1.43%*
-0.63%*
-0.25%
+1.02%*
+0.64%*
+1.15%*
-0.35%
-0.11%
+0.87%*
• There is evidence of impact on bone density caused by exposure to TDF/FTC used as PrEP over 48 weeks in
18-22 year old males
• Discontinuation of exposure to TDF/FTC leads to a trend to recovery of bone density changes over a 48
week follow-up period
Mulligan K, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Efficacy of “On Demand” PrEP with TDF/FTC
• HIV-negative MSM
• Condomless anal
sex with ≥ 2
partners within 6
months
• eGFR > 60 mL/min
• HBSAg-negative
N = 199
N = 201
TDF/FTC
On Demand
N = 362
Open-Label
TDF/FTC
On Demand
Placebo
On Demand
Feb 2012
Open-Label Extension:
• Median (IQR) age: 35 (29-43) years
• Use psychoactive drugs in past 12 mos: 43%
• Median (IQR) No. sexual events in prior 4 wks: 9.5 (5-15)
• Median (IQR) No. sexual partners in prior 2 mths: 7 (3-15)
MSM
Jun 2016
Nov 2014
(DSMB stopped)
2 tablets (TDF/FTC)
2-24h before sex
Sexual
Event
1 tablet
(TDF/FTC)
24h later
1 tablet
(TDF/FTC)
48h later
Sexual
Event
1 tablet
(TDF/FTC)
24h later
1 tablet
(TDF/FTC)
48h later
Molina JM, et
al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Efficacy of “On Demand” PrEP with TDF/FTC
Study Design
MSM
“On-demand” TDF/FTC treatment (n=199)
•
•
High-risk, HIVuninfected MSM
N=400
Condomless anal
sex with ≥2
partners within 6
months
eGFR > 60
mL/min
Double-blind,
randomised
Primary Endpoint:
HIV seroconversion
All participants received a package of
preventative measures:
• counseling
• repeated HIV testing
• screening and treatment for other STIs
• HBV and HAV vaccination
• condoms and gel
Secondary Endpoint:
Sexual behaviour,
safety events,
adherence
“On-demand” TDF/FTC placebo (n=201)
“On-demand” regimen constitutes:
• 2 TDF/FTC or 2 placebo 2 - 24 hrs prior to sexual intercourse exposure
• 1 TDF/FTC or placebo 24 hrs and then 48 hrs after first intake
October 2014 the DSMB recommended that the placebo arm be
discontinued and participants switched into the treatment arm
Molina JM, et
al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Probability of HIV-1 infection
Efficacy of “On Demand” PrEP with TDF/FTC
Results
0.20
0.18
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
16 subjects infected
• Placebo = 14 (incidence: 6.6/100 PY)
• TDF/FTC = 2 (incidence: 0.94/100 PY)
•
Mean follow-up = 13 months
•
Average 16 pills/month
•
Number needed to treated: 18
for 1 year to prevent one HIV infection
Placebo
P = 0.002†
TDF/FTC
0 2 4 6 8 101214161820222426
Months
Placebo, n
TDF/FTC, n
•
201
199
141
140
74
82
55
58
41
43
MSM
*mITT Population
†Log-rank test
86% (95% CI: 40-99, p=0.002)
reduction in MSM at high risk of
HIV infection who took on-demand PrEP
Molina JM, et
al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
MSM
HIV incidence (mITT analysis),
adherence, and sexual behavior
Open-label
Double-blind
0.19
(0.01-1.08)
TDF/FTC
0.91
(0.11-3.30)
PBO
6.60
(3.60-11.1)
Total Follow-up (py)
515
219
212
Median follow-up (months)
18.4
9.3
18
55
50
15
46
42
7786% (p=0.0003)
40.6
58
No significant change
35.2
37
HIV incidence per 100 py (95%CI)
Adherence measures:
Median pills/month (no.)
Participants with plasma TFV > 40ng/mL (%)
Correct* PrEP use at last sexual intercourse (%)
Sexual behaviour:
Change in no. reporting condomless AI (%)
Incidence rate of first STI (/100 py)
Participants with any STI (%)
*At least one pill before and one pill after
On Demand PrEP with oral TDF/FTC remained highly effective in at-risk MSM
97% relative reduction in HIV incidence vs. placebo
mITT, Modified Intention-to-Treat Population
py, patient years
STI, sexually transmitted infection
Molina JM, et
al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Evaluation of uptake of daily or intermittent PrEP
in MSM and transgendered people (TGP)
MSM &
TGP
AmPrEP:
Amsterdam PrEP
Demonstration
Project
198 MSM and TGP initiated TDF/FTC as PrEP
Characteristic
41 [34-50]
Daily PrEP
n=144
38 [33-48]
Intermittent
PrEP n=54
44 [36-55]
74 (37)
61 (42)
13 (24)
40 (20)
30 (21)
10 (20)
8 (4.0)
6 (4.2)
2 (3.7)
Median number of unique anal sex partners [IQR]1
13 [7-25]
15 [8-26]
10 [5-19]
0.017
Receptive CAS with a casual partner1 – no. (%)
134 (68)
103 (72)
31 (57)
0.058
2 [0-7]
2 [0-7]
1 [0-4]
0.037
119 (60)
84 (58)
35 (65)
0.407
Median age in years [IQR]
> 1 risk factor for HIV infection in the preceding 6
months - no. (%)
Bacterial STI at baseline - no. (%)
Hepatitis C RNA at baseline - no. (%)
Median number of receptive CAS partners [IQR]1
Sex-related drug use of 2 or more different hard drugs
Total n=198
p-value
0.015
• 73% of participants
opted for daily PrEP use
over intermittent use
(26%)
• Daily PrEP users overall
were younger (mean
age of 38 vs. 44 years)
and had a higher
number of unique
partners (mean 15 vs.
10 partners) compared
to intermittent users
STI, sexually transmitted infection; CAS, condomless anal sex
High interest in PrEP with a preference for daily use, especially in younger populations and
those who reported more sexual partners
Hoornenborg E,
et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Los Angeles
PATH-PrEP
Demonstration
Project
MSM &
TGW
Daily oral TDF/FTC use among MSM in a Los
Angeles multisite demonstration project
Open-label, two-site, 48 w demonstration project of TDF/FTC for PrEP in adult
MSM/TGW in Los Angeles
% Patients with TFV-DP (fmol/punch) at Wk 4
% Patients
• 301 HIV-uninfected MSM/TGW were
assigned to receive PrEP (N=278) or be
counseled on PEP (n=23), based on self
reported risk
85.4%
89.6%
59.1%
87.1%
• Those in PEP cohort could be moved to
PrEP cohort based on change in ongoing
risk
• Adherence was measured by self-report,
plasma TFV, TFV-DP levels in DBS, and
MEMS caps
DBS = dried blood spot
MEMS = Medication Event Monitoring System
Landovitz RJ, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Los Angeles
PATH-PrEP
Demonstration
Project
MSM &
TGW
Daily oral TDF/FTC use among MSM in a Los
Angeles multisite demonstration project
Predictors of lack of protective TFV-DP levels by DBS at week 4
Population
Non-Hispanic black participants
(n=40)
Reporting sex for trade in the past
month (n=27)
Lower income, $20-50k (n=109)
AOR
95% CI
p
0.24
0.09-0.78
0.007
0.3
0.09 - 0.98
0.01
0.3
0.09 - 0.97
0.02
AOR, Adjusted Odds Ratio
There is significant community interest in PrEP among a diverse MSM
community and good adherence in most men; barriers to adherence in more
marginalised populations, black MSM, those with low-income, and sex
workers, need to be addressed.
Landovitz RJ, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Daily vs nondaily PrEP dosing in African women
MSM &
TGW
HPTN 067 / ADAPT
(Cape Town)
Phase 2, randomised, open-label trial of PrEP
HIV-uninfected women who
have sex with men and
transgendered women in
Cape Town, South Africa
N=179
DOT x
6 weeks
24 weeks
(D) Daily TVD
(n=60)
24 weeks
(T) Twice-weekly + postintercourse boost TVD
(n=59)
24 weeks
(E) Event-driven, before and
after intercourse TVD
(n=60)
Primary Endpoints:
Feasibility of intermittent dosing of PrEP regimen in women
PK steady state after DOT X 6 weeks
Bekker L, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
HPTN 067 / ADAPT
(Cape Town)
Daily PrEP offers better coverage and enhances
adherence compared with nondaily PrEP in African
women
Randomisation at 6 weeks*
Daily
(D)
Time-Driven
(T)
Event-Driven
(E)
Subjects, n
60
59
60
HIV seroconversions, n
1
2
2
NS
7441
2850
2002
<0.001
76
65
53
<0.001
Percentage with detectable drug levels when
reporting sex in last 7 days: Week 10; Week 30
93; 80
87; 63
78; 53
0.018
Percentage with ≥ 9.1 fmol/106 cells in PBMC when
reporting sex in last 7 days: Week 10, Week 30
81; 66
52; 46
54; 32
0.003
75
58
52
<0.001
Pills used, n
Adherence, %
Sex events fully covered, %
MSM &
TGW
P
Time-Driven (T) means twice
weekly with a postintercourse boost
Event-Driven (E) means before
and after intercourse
Daily dosing compared to Time-Driven or Event-Driven resulted in:
• Better adherence
• Higher drug levels
• Better coverage of sex acts
Bekker L, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Partners
Demonstration
Project
Integrated delivery of PrEP and ART: Sustained near elimination
of HIV transmission in African HIV serodiscordant couples
Discordant
Couples
Open-label, prospective interventional study of integrated ART and PrEP delivery for
HIV prevention among N=1013 heterosexual high risk HIV serodiscordant couples
PrEP as a Bridge to ART
HIV+ partner
HIV- partner
HIV Incidence:
Expected and Observed
ART
PrEP
PrEP prior to viral
suppression in HIV+
partner
Protection through
sustained ART use →
6
5
N=83 infections
Incidence = 4.9
(95% CI 3.9-6.0)
6 Months
4
HIV+ partner
HIV- partner
ART
delayed
ART
PrEP
PrEP prior to ART initiation and
then prior to viral suppression in
HIV+ partner
6 Months
Protection through
sustained ART use →
2
N=4 infections
Incidence = 0.2
(95% CI 0.1-0.6)
1
0
Integrated delivery of ART and PrEP in HIV serodiscordant couples demonstrated:
•
•
95% reduction
(95% CI 87-89%)
P<0.0001
3
Expected
95% reduction in observed HIV incidence compared to expected
time-limited PrEP as a bridge to ART is feasible and highly effective in preventing HIV transmission
Observed
Baeten J, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Discordant
Couples
Should TasP and PrEP be used in
combination for serodiscordant couples?
HIV prevention effect
with high adherence
TasP
PrEP
96-100%
90-100%
(HPTN 052, Partner Study )
Near universal adherence
(Partners PrEP, iPrEx/iPrEx OLE)
Objective evidence of good
adherence
Pros:
Cons:
• May decrease stress, fear, and guilt and anxiety
• May increase sexual pleasure and intimacy
• Increased control over preventing one’s own HIVInfection
• Possible protection when infected partner delays
or declines ART
• Question of how much added protection
• Uncertainty about cost or insurance coverage
• Possible AEs
Baeten, J, et al. R4P 2014
Koester K. IAC 2014
Baeten J, et al. CROI 2015
Rodger A, et al. CROI 2014
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Partners
Demonstration
Project
PrEP with TasP for HIV serodiscordant
couples
Discordant
Couples
PrEP is offered as a ‘bridge’ for the first 6 months
after ART initiation by the HIV-infected partner
• Residual risk of HIV-1 transmission can
continue for the first 6 months of ART,
prior to viral suppression
• For couples initiating ART at enrollment,
PrEP is offered through 6 months, then
stopped
• Couples in which the infected partner
delays or declines ART, PrEP is continued
until 6 months after ART initiation
ART
PrEP
Stop
ART delayed
ART
PrEP
Baeten J, et al. CROI 2015
Mujugira A, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Discordant
Couples
PrEP with TasP: HIV incidence
Partners
Demonstration
Project
6
N=39.7 infections
Incidence rate=5.2
Limited PrEP use in the two HIV
seroconverters. Both had:
(95% CI: 3.7-6.9)
HIV incidence rate
5
IRR observed vs. expected =
0.04 (95% CI: 0.01-0.19)
or a
4
96% reduction (95% CI 81-99%)
P<0.0001
3
• Undetectable plasma TFV
concentrations at the time of
seroconversion
• Partners that were not known to be
virologically suppressed
2
N=2 infections
Incidence rate=0.2
1
(95% CI: 0.0-0.9)
0
• Started PrEP but reported breaks in use
Expected
Incidence Model
Observed
Incidence
The observed HIV incidence is a 96%
reduction compared to the expected
incidence rate
Baeten J, et al. CROI 2015
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Recruitment of higher-risk couples
HIV risk is heterogeneous, even in
at-risk populations
Eligibility for the Partners Demonstration Project
included only couples with scores ≥5
HIV-1 Incidence, per 100 Person-years
Partners
Demonstration
Project
Discordant
Couples
Risk Score
*Score ≥5 = 41% of the total population
Baeten J, et al. CROI 2015
Kahle, E. JAIDS 2013
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Quantifying individual and public health
benefits of PrEP
Number need to treat
75
55
Benefits of
PrEP
Insertive anal intercourse without a condom
2-5 partners >5 partners
Receptive anal intercourse
without a condom with a
partner of unknown serostatus
HIV-positive partner
Self-reported STI
35
Receptive anal intercourse with or
without a condom (combined)
Syphilis
Receptive anal intercourse without a condom with an HIV-positive partner
Receptive anal intercourse without a condom with an HIV-negative partner
Cocaine
15
0
10
20
30
40
50
60
70
80
In iPrEx, subgroups with
strong risk factors for HIV
(new syphilis,
drug use, sex with known
HIV+ partner) had very
low number needed to
treat (NNT), suggesting
individual benefit from
PrEP
Population attributable fraction (%)
Buchbinder S, et al. Lancet 2014
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Quantifying individual and public health
benefits of PrEP
Number need to treat
75
55
Benefits of
PrEP
Insertive anal intercourse without a condom
2-5 partners >5 partners
Receptive anal intercourse
without a condom with a
partner of unknown serostatus
HIV-positive partner
Self-reported STI
35
Receptive anal intercourse with or
without a condom (combined)
Syphilis
Receptive anal intercourse without a condom with an HIV-positive partner
Receptive anal intercourse without a condom with an HIV-negative partner
Cocaine
15
0
10
20
30
40
50
60
70
The largest PAF was for
men who had RAI
without a condom,
regardless of HIV status
of partners (HIV+, “HIV-”,
or HIV-unknown).
Even in this group, the
NNT was only 36
80
Population attributable fraction (%)
Buchbinder S, et al. Lancet 2014
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Eliminating barriers to increase uptake of PrEP in
a community based clinic in San Francisco
San Francisco AIDS
Foundation
Successful implementation of PrEP program in a LGBTQ-friendly nurse-led
sexual health clinic
Nurse-Led LGBTQ Health Center providing:
• Sexual Health Services
• MH/SA Services
• Community Engagement Programs
Clinic screened 1252 patients with 95.5% enrolling in
PrEP Program
97.7% cis-gender MSM
0.3% trans-gender Male having sex with male
21% had STI at baseline
Mean number of sexual partners (last year) - 17.4
92.7% reported having condomless sex
Incidence of STI
25%
20%
3.0%
15%
2.2%
2.6%
14.3%
10.9%
11.8%
4.8%
3.0%
2.1%
10%
•
•
•
•
•
Barriers to
PrEP
services
9.8%
10.0%
2.2%
3.0%
6.7%
0.0%
9.5%
5%
3.8%
0%
2.2%
4.2%
3.2%
4.8%
Baseline Month 1 Month 4 Month 7 Month 10 Month 13 Month 16
n=1252 N=921
N=549
N=340
N=200
N=90
N=21
Syphilis Any Stage
Pharyngeal, Urethral or Treated for Contact to an STI
Rectal STI
Gibson S, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Eliminating barriers to increase uptake of PrEP in
a community based clinic in San Francisco
San Francisco AIDS
Foundation
Programme provides:
• POC labs
• PrEP counsellors
• Benefit navigators
• Follow up services
Over 90% adherence rates
No HIV infections so far in patients
taking PrEP
Barriers to
PrEP
services
Self-Reported Adherence Rates
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
3%
2%
5%
4%
7%
3%
6%
3%
5%
3%
0%
95%
91%
90%
91%
92%
100%
Month 1
N=921
Month 4
N=549
Month 7
N=340
3 or Less Missed Doses in Last 7 Days
Month 10 Month 13 Month 16
N=200
N=90
N=21
4 or More Missed Doses in Last 7 Days
Not Reported
Gibson S, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Barriers
and Quality
of Care
Correlates for levels of self-reported PrEP
adherence among black MSM in three U.S. cities
HPTN073: 3 US City
Demonstration
Project
US demonstration project of once daily TDF/FTC for PrEP in N=226 Black MSM (BMSM)
Washington, D.C., Los Angeles, CA, and Chapel Hill, NC
• Participants offered client-centered care
coordination (C4): individualised prevention
counselling, support, and service coordination
• 40% age <25yrs
• 79% of participants chose to initiate PrEP
• 92% of PrEP initiators retained after 12-months
follow up
• PrEP initiators more likely to have utilised the C4
system (OR=12.6; 95%CI: 2.45-64.5, p<0.01)
Providing theory-based, culturally tailored
programmes for Black MSM can potentially
increase PrEP initiation, optimise PrEP adherence,
support PrEP programme retention, and prevent
HIV infection
Adherence and Biomarkers of PrEP Use
≥ 90% self-reported
adherence
Detectable TFV-DP in PBMC
Any drug
Week 8
Week 26
Week 52
67% (99/148)
62% (86/139)
67% (69/103)
80%
76%
68%
≥4 days/
week
61%
63%
56%
• Self-reported adherence correlated well with adherence as
measured by drug levels
• Approx. 60% of participants took 4 or more PrEP doses/week
Wheeler D, et al. AIDS 2016
Hucks-Ortiz, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
ART, UTT
Immediate (IMM) vs. Deferred (DEF) ART initiation
START Subgroup
analysis
START is an international randomised trial comparing
immediate ART (CD4 > 500 cells/µL) (n=2326) vs. deferred ART (CD4 < 350 cells/µL) (n=2359)
• Primary analysis showed in the immediate
treatment arm:
• Overall 57% reduction in events
• NNT=128
• There was no subgroup where Deferred therapy
had a lower Absolute Risk Rate (ARR) compared to
Immediate therapy
• The highest ARR was found for subjects who were
older, had low CD4:CD8 ratios, had higher
Baseline HIV RNA, and had higher Framingham
risk scores.
Primary endpoint: a composite of a serious AIDS or non-AIDS event, or death
Subgroups were defined by 8 predefined baseline characteristics: Age, Sex,
Race, Geographic region, BL CD4, BL VL, Smoker, Framingham 10 year risk of
CHD
Subgroup
P-val.
ARR (Rate DEF-IMM With
NNT Homo95% CI)
geneity
Pct. In No. of Patient with Events
(Rate per 100 PY)
Group
IMM. ART
DEF. ART
Age (years)
≥50
11.8
14 (1.78)
31 (4.03)
45
1.67
Baseline CD4:CD8 Ratio
<0.5
27.8
7 (0.36)
21.7
60
0.06
1.48
11 (0.71)
32 (2.19)
67
Framingham 10-year risk of CHD
≥10
9.6
0.13
13 (1.90)
1.45
23 (3.34)
-1
Deferred ART better
Subgroup analysis in the START study supports overall
conclusion that immediate treatment is favoured over
deferred treatment
0.005
40 (2.03)
Baseline HIV RNA (cp/mL)
>50K
0.01
2.24
0
1
2
69
3
4
5
Immediate ART better
NNT, number need to treat immediately for one year to prevent one event
ARR, absolute risk reduction
HR, hazard ratio
Molina JM, et al. AIDS 2016
Southern African HIV Clinician Society/Wits RHI: 2 February 2017
References
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Conference, Durban 2016.
• McCallister S, et al. HIV-1 Seroconversion Across 17 International Demonstration Projects with Pre- Exposure Prophylaxis
(PREP) with Oral Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF). ASM Microbe. June 16-20, 2016.
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Seattle, 2015.
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Southern African HIV Clinician Society/Wits RHI: 2 February 2017
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• Mujugira A, et al. Other HIV PrEP studies at CROI 2015: Implementation of oral PrEP and problems with tenofovir gel
CROI, Seattle. 2015
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study. CROI, Boston. 2014
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Southern African HIV Clinician Society/Wits RHI: 2 February 2017
Acknowledgements
With thanks to:
The Southern African HIV ClinicianS Society
Wits Reproductive Health and HIV Institute
Gilead Sciences PrEP Resources
Southern African HIV Clinician Society/Wits RHI: 2 February 2017