PrEP in 2018 and Beyond

PrEP in 2018 and Beyond
Trevor Hawkins MD
Senior Director, Medical Affairs,
Gilead Sciences, Foster City, CA

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2
HIV Prevention: The Big Picture
 Prevention Gap Report (UNAIDS, 2016): Efforts to reach fewer than
500,000 new HIV infections by 2020 are off track
 Huge successes in treatment uptake-19 million on ART.
 Decline of new HIV infections is substantially slower than the fall in
AIDS-related deaths, and epidemic control remains out of reach
 Accelerated decline in new HIV infections is required to avoid a
rebound of the epidemic, especially among key populations. It is
possible that we could lose control of the epidemic, especially in young
people.
Gilead confidential and proprietary-for internal use only

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3
If we use the Tools
3
UNAIDS, 2015 estimates from the AIDSinfo online database. Gilead Sciences Confidential - For Advisory Purposes Only

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4
Between 2008-2014, incident HIV infections fell from 45,700 to 37,600
Heterosexuals
8,600 infections
(36% decline since 2008)
CDC: HIV Incidence Down 18% in US Between 2008-2014
CDC National HIV Surveillance System Data
Though HIV incidence has declined in the population as a whole in the US,
HIV in MSM remained stable and increased in some subpopulations.
Southern states comprised 50% of all new HIV infections in 2014.
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People who inject drugs
1,700 infections
(56% decline since 2008)
Gay and bisexual men
who inject drugs
1,100 infections
Gay and bisexual men
26,200 infections
(Stable since 2008)
• Proportion of MSM estimated to be living
with HIV but not yet diagnosed:
o Black 20.4%; Latino 20.9%; White 12.5%
• Incident HIV infections:
o Remained stable in Black MSM
o Increased 20% in Latino MSM
o Decreased 18% in White MSM
39,393 New HIV Infections in 2015a
New HIV infections decreased in many
MSM, but rose in MSM aged 25-34.
13-24 25-34 35-44 45-54 ≥55
23%
70%
a. Data has been statistically adjusted to account for missing transmission category.

New Zealand
Nigeria
Norway
Peru
South Africa
Swaziland*
South Korea
Taiwan
Truvada approved for prevention1
Regulatory Status of Truvada for PrEP
Updated Feb 2018
Regulatory application submitted for a
prevention indication for Truvada2
Equador
Australia
Brazil
Canada
Chile
France (RTU)
Hong Kong
Israel
Kenya
Lesotho*
Malawi
Tanzania
Thailand
Uganda
United States
Zambia
Zimbabwe
*Approved via import license from South Africa.
• The European Commission granted Gilead
marketing authorization for Truvada as PrEP in Q3
2016. This should encourage countries within the
EU to make PrEP available within their national
health systems, based on cost factors and
individual country regulatory requirements. Gilead Confidential

Gilead Confidential and Proprietary—for Internal Use Only
‡
National - Truvada for PrEP Trends for December 2017
Individuals Taking TVD for PrEP (Active) (K) Individuals Initiating Truvada for PrEP
Dec 2017: 8,320
YTD 2017 Avg:
8,990
(+16% vs 2016)
Over 2017, active writers (3 PrEP/12 months) grew by 48% to 8.6K and total PrEP writers
(1 Rx/12 months) increased ~2 fold (19K to 38K)
6

The Potential Role of PrEP in Reducing New HIV Infection
7
Buchbinder S, et al. CROI 2018. Boston, MA. Oral #87.
Citywide initiative to increase PrEP uptake in high risk HIV-negative individuals as well as
increase rapid ART initiation and improve the care continuum in PLWHIV
PrEP use in San Francisco has been increasing over time. This effort, in combination with
improving the treatment cascade, is associated with a significant decrease in new HIV
infections.
Getting to Zero San Francisco
• Based on 2 surveys, 37-45% of HIV negative MSM on PrEP in last year.

Decreases in HIV Incidence Coincide with Expanded PrEP Use
8
Retrospective study from the research database of Clinique médicale l’Actuel,
2011-2016
Beauchemin M, et al. CROI 2018, Boston, MA. Poster #1037.
Efforts should be made to further increase accessibility of combined
prevention measures in semi-urban/rural areas in Quebec and among youth
and older populations, who may be less aware of the availability and
effectiveness of PrEP
Clinique médicale l’Actuel, Montreal, Quebec

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9
Rapid Reduction in HIV Diagnoses After PrEP Implementation
Statewide pragmatic PrEP implementation study in high risk individuals looking at population
effect of rapid, targeted, high-coverage PrEP roll-out, (N=3700)
 In NSW, 80% of HIV infections are in MSM and the rate has been stable
– N=3602 included in analysis of HIV incidence
– 74% (n=2754) retention on PrEP through 12 months
Grulich A, et al. CROI 2018. Boson, MA. Oral #88. 9
New South Wales, Australia
Primary Outcome 2: Populations Level
Change in NSW HIV diagnoses in MSM
Recent (Last 12 Months) Infections All HIV Diagnoses
Before (n) After (n)
Percentage decline
(95% CI)
Before (n) After (n)
Percentage decline
(95% CI)
149 102 32% (24-40%) 295 221 25% (20-30%)
Primary Outcome 1: Cohort Level
Change in Incidence Rate after intervention
Rates
Cohort Incidence Rate (n=2)* 0.5/1000 PY
Expected Rate 2/100 PY
*2 confirmed new HIV infections over 3,927 person-years: 1 was dispensed
but never commenced PrEP; 1 took no PrEP for months prior to infection
Targeted PrEP roll-out at scale led to a substantial decline in new
HIV infections at the statewide level.

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10
About AIDSVu
Siegler AJ, et al, CROI 2018. Boston, MA. Poster #1022LB.
 Partnership since 2010 between
Gilead Sciences & Emory
University’s Rollins School of Public
Health
 Mission to make HIV data widely
available, easily accessible &
locally relevant to inform public
health decision making
 Interactive online mapping tool to
visualize the U.S. HIV epidemic at
state-, county- & ZIP code-level
10

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11Siegler AJ, et al, CROI 2018. Boston, MA. Poster #1022LB. 11

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12
Priority Populations: Targeting Populations at Risk and
Geographic Areas of Greatest Need
Population by Race/Ethnicity
1) US Census American Fact Finder, 2015
2) CDC HIV Surveillance Report, 2014; November 2015
3) Bush S, et al. ASM 2016; based on 43.7% of unique FTC/TDF for PrEP starts 2012-Q3/2015
Focus on MSM of color, the South, women
(cis and transgender)
New Infections by
Race/Ethnicity
PrEP Uptake by
Race/Ethnicity
Top 10 MSA’s for HIV Incidence
1. Baton Rouge, LA
2. Miami, FL
3. New Orleans, LA
4. Jackson, MS
5. Orlando, FL
6. Memphis, TN
7. Atlanta, GA
8. Columbia, SC
9. Jacksonville, FL
10. Baltimore, MD
Men are 70% of PrEP Users

Drug Utilization in the United States: Latest 12 Months
Five Areas: West Manhattan, Chicago North, San Francisco North, Boston and Seattle
account for 31% of total volume prescribed for Truvada for PrEP
Source: R12M Mar’16 – Feb’17 SHA PTD Claims Data.
Midwest 14.3% Southeast 14.6% Central 18.4% West 24.5% Northeast 28.3%
Houston-New
Orleans
3.4%
Washington
North
3.3%
Chicago
North
6.7%
San Francisco
North
6.2%
West
Manhattan
7.6%
Dallas 2.9%
Washington
South
3.1% Atlanta 4.0% Seattle 4.6% Boston 5.7%
Las Vegas-
Phoenix
2.4% Palm Beach 2.5%
Columbus-
Pittsburgh
2.7% Los Angeles 3.6% Midtown East 4.3%
Minneapolis 2.3%
Orlando-
Tampa
2.0%
Chicago
South
1.8% Torrance 2.7%
Upper
Midtown
3.9%
Austin 1.9%
Durham-
Charlotte
1.5%
Cleveland-
Detroit
1.8%
San Francisco
South
2.5% Philly-NJ 3.2%
Denver 1.3% Miami 1.4% Milwaukee 1.4% San Diego 2.1%
Upper
Manhattan
2.2%
Baltimore 0.7% Irvine 1.7% Brooklyn 1.4%
East Bay 1.3%
Confidential - For Internal Use Only
Regional Contribution of Truvada for PrEP

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14
Estimated Number of Adults with PrEP Indications, US,
2015, Comparison of Results from Two Methods
1
CDC
MSM HET PWID Total*
Updated CDC
Estimate
814,000 258,000 73,000 1,145,000
Previous CDC
Estimate
492,000 624,000 115,000 1,232,000
Black and Hispanic* 65.1% 81.8% 57.1%
*Estimates are rounded and may not sum to the total.
Smith D, et al, CROI 2018. Boston, MA. Poster #86.
• # Black/Latino/PWID with PrEP indications =
• state % Black/Latino/PWID HIV dx of all MSM with HIV dx *
• # MSM/HET/PWID with PrEP indications

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Preliminary Estimate of Minimum PrEP Coverage by US
Region and Race/Ethnicity, 2015-2016
15
CDC
 Denominator:
– Number of persons with
indications for PrEP, 2015
 Numerator:
– Number of persons
prescribed TRUVADA for
PrEP, US
– Symphony Health
Analytics, September 2015-
August 2016
– Race/ethnicity available for
66%
29
3
2
1
2
0
5
10
15
20
25
30
35
Northeast Midwest South West
%PrEPCoverage
White Black Hispanic All race/ethnicities
Nationwide, 14% of White, 1% of Black, 3% of Hispanic, and 8% of all persons
estimated to have indications for PrEP were prescribed PrEP.
Smith D, et al, CROI 2018. Boston, MA. Poster #86.

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Individual and Network Drivers of Racial Disparities
Among YMSM-Longitudinal Cohort Study of YMSM (16-
29 Y/O) Living in Chicago (N=1015)
Compared to White and Latino
subjects, YBMSM had:
 A higher prevalence of both HIV
(32%; p<0.001) and rectal STIs
(26.5%; p=0.011)
 Lower rates of participation in
sexual risk practices (p<0.001)
 Greater number of lifetime HIV
tests (p<0.001)
 Less likely to achieve viral
suppression (p=0.01)
 Greater racial homophily with
sexual partners (p<0.001)
 Had stronger relationship ties
(p<0.001)
 Greater levels of:
– Stigma (p<0.001)
– Victimization (p=0.04)
– Trauma (p<0.001)
– Childhood sexual abuse (ever)
(p<0.001)
Mustanski B et al. CROI 2018. Boston, MA. Poster #906. 16
.

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Black and Latino MSM
 Stigma
– Medical mistrust
– Identity/socialization factors
– Recent healthcare experiences
 Lack of cultural sensitivity
 Slow uptake is intrinsically linked to larger issues around why Black
and Latino MSM have higher rates of HIV; higher rates of
incarceration, lower education, domestic and street violence, higher
unemployment and housing instability
Barriers to PrEP Engagement

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Estimated New HIV Infections in the US, by Age, 2014
174 35
1,828
7,868 7,870
6,026
4,662
4,196
4,021
3,242
2,166
1,069 914
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
<13 13-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 >65
EstimatedNewHIVinfections,n
Centers for Disease Control and Prevention. HIV Surveillance Report, 2014; vol. 26. http://www.cdc.gov/hiv/library/reports/surveillance/. Published November 2015. Accessed April 13, 2016.
22%
17%
Persons <25 and >50 years old comprised almost 40% of new HIV infections in 2014.

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24%
76%
11%
89%
83,672 Men15,060 Women
Age of FTC/TDF for PrEP Users in US
2012-2016
 Mean age of 98,732 unique individuals: 37.3 years + 11.8
Average Age 37.7
2012 39.4
2016 37.1
<25 years
≥25 years
Average Age 35.0
2012 34.5
2016 36.7

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The Adolescent Brain is Different from the Adult Brain
 Less developed frontal lobe capacities for executive function,
impulse control, long-term decision making
 More developed limbic lobe favoring emotions, impulsive behavior
and short-term gratification
Information alone will not diminish risk-taking

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Safety and Efficacy of FTC/TDF for PrEP in MSM Aged 15-
17 in the United States*
Open-label, multi-site US demonstration project of
Truvada for PrEP in 15-17yo MSM, n=79
ATN 113: PrEP Demonstration Project and Safety Study
• Sharp drop in adherence when transitioning
from monthly to quarterly follow-up
• 95% had detectable drug when monitoring was monthly
• Unlike ATN 110 (18-22yo), drop in adherence was
consistent across all races/ethnicities
• Compared with adherent participants, non-
adherent participants tended to be more likely
to endorse the beliefs:
• “I worry others will see me taking pills and think I am
HIV-positive” (p=.03)
• “I am concerned people will know I have sex with other
men because I’m taking PrEP” (p=.06)
• “I don’t like taking pills” (p=.06)
• 3 seroconversions occurred in 3
adolescents with no detectable TFV
• HIV incidence = 6.41/100py (95% CI: 4.9-25.8)
Adherence:
TFV-DP (fmol/punch) via DBS w/ Dosing Estimates
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Wk 4 Wk 8 Wk 12 Wk 24 W36 Wk48
>700 (4 or
more days)
350-699
(2-3 days)
<350
(2 days)
BLQ
60 52 55 32 23 28
TFV Levels in Seroconverters
0
200
400
600
800
1000
1200
Wk 4 Wk 8 Wk 12 Wk 24 Wk 36 Wk 48
Pt 1 (wk 32)
Pt 2 (wk 36)
Pt 3 (wk 48)
21
TFV-DPLevel 4+ doses
*TDF/FTC is not FDA approved for use in those <18 years oldGilead confidential and proprietary-for internal use only

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Men and Women Starting FTC/TDF for
PrEP in US, 2012 to 2015
2,740 3,708
5,051
7,313
3,470
5,315
16,855
35,232
0
5000
10000
15000
20000
25000
30000
35000
40000
2012 2013 2014 2015
4-YearTotal: 79,684
6,210
Women: 18,812
Men: 60,872
9,023
21,906
42,545
FTC/TDF (Truvada) for HIV Pre-Exposure Prophylaxis
(PrEP) Utilization in the United States: 2012−2015
Truvada® (FTC/TDF) for HIV Pre-Exposure Prophylaxis
Mera R, et al. AIDS 2016. Durban, South Africa. Oral #TUAX0105LB
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HIV Biomedical Prevention Knowledge, Attitudes, and
Behavior Among U.S. Women
23
Kassaye S, et al. CROI 2018, Boston, MA. Poster #1050.
Cross sectional survey among women enrolled in WIHS to assess PEP, PrEP, and TasP
knowledge, attitudes, and behavior, 2015-2015, (N=2406)
Knowledge and use of PEP/PrEP was limited among women, but upon learning about
these methods the majority were willing to use and recommend them.
Women’s Interagency HIV Study (WIHS)
HIV (-) HIV (+) Total
Heard of PrEP
10% 16% 14%
Heard of PEP
17% 21% 20%
Would Use PrEP
68% - -
Would Use PEP
(if recommended
by a doctor)
61% - -
Willing to
undergo regular
HIV Testing
72% - -
Reasons for taking daily PrEP % of participants
“Protecting myself” 83
Having a casual partner 40
Distrust of partners 46
Having an HIV+ partner 26
Recommended by HCP 30
Factors associated with willingness to use PrEP
Younger age (OR: 0.95; 95% CI: 0.92-0.98, p=0.001)
Believes PrEP will prevent HIV (OR: 7.53; 95% CI: 2.02-28.13; p=0.0027)
Willingness to recommend PrEP to others (OR: 40; 95% CI: 21.28-76,92;
p<0.001)

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Predictors of Willingness to take PrEP among Black and
Latina Transgender Women (BLTW)
Descriptive analysis of a 2-city cohort to estimate PrEP uptake and identify
predictors of willingness to take PrEP among BLTW
24
Baltimore, MD; Washington DC
 Results
 201 BLTW, 86% (n=174) reported
awareness
– 80% (n=139/174) willing and knew where to get PrEP
 Among 76 HIV-negative/unknown who had
not taken PrEP, 78% (59/76) were willing
but only 39% (30/76) took PrEP
 History of exchange sex and legal gender
affirmation were predictors of PrEP
willingness
 Reported reasons for unwillingness include:
hormone interactions, Truvada side effects,
and requiring daily doses
Poteat T, et al. CROI 2018. Boston, MA. poster # 1045
PrEP uptake improvement requires understanding the complex relationships
between gender affirmation, exchange sex and PrEP acceptability among BLTW

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Characteristics of Seroconverters
HIV Seroconversion Across 32 FTC/TDF PrEP Demonstration Projects
Geography (N=67)Race (N=67)
Mixed
(23)
Black
(25)
White
(14)
NR (4)Asian (1)
MSM
(54)
 Mean age: 25.3 y (range: 17–49)
 Risk: MSM (81%); Race: Black (37%), Mixed (34%); Location: US (43%), SA (39%)
 Dried blood spot data available for 32 of 67
– 17 of 32 had TFV-DP levels BLQ
– 14 had TFV-DP levels corresponding to <2 FTC/TDF tablets per week
USA
(29)
Peru
(18)
Brazil (5)
UK (5)
S. Africa (3)
Ecuador (3)
NR (2)
Thailand (1)
Australia (1)
Female
n=1388
Male
n=7002
Transgender
n=76
FTC/TDF Exp 787.7 PY 6213.9 PY 48.4 PY
Seroconverters 2 64 1
# /100 PY
(95% CI)
0.25
(0.03-0.92)
1.03
(0.80-1.32)
2.07
(0.05-11.52)
Poor adherence is associated with an increased likelihood of seroconversion
McCallister S, et al. ASM 2016. Boston, MA. Oral
Risk Category (N=67)
MSM=64
Hetero. Women
(2)
Bisexual 1

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Time to Protection with Daily Dosing of Truvada® for PrEP
 WHO recommends additional HIV prevention measures should be
used for 7 days after starting daily PrEP1
 Target ratios have been defined for TFV and FTC for adequate cellular
protection in genital tissue2
TRUVADA for PrEP™
1. WHO Implementation tool for pre-exposure prophylaxis (PrEP) of HIV infection. Module 1: Clinical.Geneva: World Health Organization; 2017 (WHO/HIV/2017.17)
2. Cottrell M, et al J Infect Dis. 2016 Jul 1;214(1):55
3. Kashuba A, IAS 2017, France, Paris. Symposium #MOSY0803
 Time to maximal
protection is achieved by
3rd dose in FGT and by
2nd dose in RT3, well
within the WHO
recommendation of 7
days post-PrEP initiation
0
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
%AchievingEC95TargetRatio
Dose
Female Genital Tissue
(FGT)
Rectal Tissue (RT)
Maximal Protection by dose 2 in RT
Maximal Protection by dose 3 in FGT
SS % Achieving
Target in FGT
SS % Achieving
Target RT
SS, steady state

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HIV Diagnoses Among People Who Inject Drugs (PWID)
Trends in HIV diagnoses among PWID aged ≥13 years
Lyss S, et al. CROI 2018, Boston, MA. Poster #970.
‡
The increase in HIV diagnoses among PWID between 2014-2016 in certain groups require
careful monitoring of HIV incidence, outbreak planning, and rapid, multi-modal interventions.
National HIV Surveillance System (NHSS) – United States, 2010-2016
The decline in HIV diagnoses among PWID have
slowed and perhaps stalled.
Patterns of HIV diagnoses among PWID have changed

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HIV Transmission Potential due to Injection Drug Use
in Rural West Virginia, 2017
Epidemiologic review (contact tracing) of an HIV infection cluster in historically low HIV-
prevalent counties in West Virginia
28
In the context of the rural opioid epidemic in the United States, timely public health
response to clusters of HIV infection in low prevalence populations is critical to
prevent HIV outbreaks among people who inject drugs.
• Most diagnoses were due to male-to-
male sexual contact, but the potential for
transmission through IVDU was
identified
• 45 subjects identified with HIV of
which 87% were male, 71% were
white and 67% were MSM. 20%
presented with AIDS at diagnosis
• 13 of 84 persons ( includes
contacts) interviewed had injected
drugs in the past year
Hogan V, et al. CROI 2018. Boston, MA. Poster #976LB
n = 27
HIV-positive
persons
diagnosed in
2017 interviewed
and not virally
suppressed
n = 17/27
Had ≥ 1 sexual or
IDU contacts with
negative or
unknown HIV
status
n = 2/17
Had ≥1 contacts
who injected
drugs and shared
equipment in the
past year
n = 3/17
Injected drugs
and shared
equipment in the
past year
Risk behaviors that could result in bridging of HIV to the PWID population

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• Individuals at high risk of acquiring HIV may continue high risk
behavior after PrEP initiation.3
• Number of sexual partners may remain stable or may increase.3,4
• Number of condomless sexual partners may increase.3,5
• Urethral, rectal, and pharyngeal STI screening is recommended every
3-6 months.2
• High STI rates in this population may be observed due to selection bias.6
• Increased screening may decrease STI incidence in this population.6
TRUVADA for PrEP™ is recommended for appropriate HIV-negative
individuals who report diagnosis of an STI or infrequent condom
use1,2.
Changes to Sexual Behavior and STI Incidence Vary
• Some real world studies identified an association between
FTC/TDF initiation and increased STI incidence.4,7-9
• Some real world studies found no association between
FTC/TDF use and STI incidence.5,10-12
HIV incidence decreased regardless of
sexual behavior, condom use, or STI
incidence.
1. TRUVADA Prescribing Information. Gilead Sciences, Inc. 2017. 2 USPHS. Pre-exposure prophylaxis for the prevention of HIV infection in the United States–2017.
https://www.cdc.gov/hiv/pdf/guidelines/cdc-hiv-PrEPguidelines-2017.pdf 3. Montano M, et al. CROI 2017; Seattle, WA. Poster #979 4. Kojima N, et al. ID Week 2016; New Orleans, LA. P504 5. White
E, et al. IAS 2017. Paris, France. Oral #TUAC0101 6. Jenness SM, et al. CROI 2017. Seattle, WA. Poster #1034 7. Mayer K, et al. IDWeek 2016; New Orleans. Oral #2379. 8. Marcus J, et al. JAIDS
2016: epub ahead of print 9. Beymer M, et al. IAS 2017. Paris, France. TUPEC0779 10. Liu A, et al. JAMA Intern Med 2016; 176(1):75-84. 11. Crouch PC, et al. IAS 2017. Durban, South Africa.
FRAE0104 12. Nakelsky S, et al. IAPAC 2017. Miami, FL. Poster #316
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High Risk
Population
Condom Use/
Sexual
Behavior May
Vary
Increased
Screening
STI Incidence
Varies
HIV Risk
Reduction

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Combining TRUVADA for PrEP with STI Screening
Could Decrease STI Rates
Model of co-circulating HIV, gonorrhea (NG), and chlamydia (CT) infections among
MSM in the United States based on social networks
The study suggests that the high STI rates among PrEP users may not be attributable to
Risk compensation, and may be a result of selection bias (i.e. higher risk population at
baseline combined with more frequent screening).
Method: TRUVADA indications modeled
based on CDC guidelines, adherence
based on the PrEP Demo Project, efficacy
based on iPrEx.
Results:
• Increased uptake of PrEP coupled with
routine STI screening and treatment could
lead to strong and sustained declines in
gonorrhea and chlamydia incidence and
prevalence among MSM
• At 40% TRUVADA coverage and 40% Risk
Compensation 42% of GC and 40% of CT
infections would be averted over 10 years
• A doubling in risk compensation would still
result in net STI prevention relative to no
TRUVADA
• Performing STI screening at quarterly vs.
biannual intervals would result in a further
50% reduction in incidence
Jenness SM, et al. CROI 2017. Seattle, WA. Poster #1034
RiskCompensation
% of NG Infections Averted % of CT Infections Averted
PrEP Coverage PrEP Coverage
20%
20%
40% 60% 80%
40%
60%
80%
20% 40% 60% 80%
20%
40%
60%
80%
RiskCompensation
20% 40% 60% 80%0%20% 40% 60% 80%0%
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HIV Pre-Exposure Prophylaxis as a Gateway to Primary Care
Cross-sectional study of PrEP vs. non-PrEP users at Fenway Health to determine
association of PrEP with receipt of routinely recommended primary care (N=5,857)
Marcus JL, et al. CROI 2018, Boston, MA. Poster #1011.
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54
87
90
78
17
77
33
67
62
42
14
37
0
20
40
60
80
100
Influenza
Vaccination
Tobacco
Screening
Depression
Screening
HbA1c or
Glucose
Testing
HbA1c
Testing
Glucose
Testing
%ofpatients
PrEP No PrEP
PrEP use was associated with receipt of routinely recommended primary care.
The benefits of PrEP may extend beyond HIV prevention to behavioral and mental
health, and treatment and prevention of other infectious and chronic diseases.
Receipt of primary care by PrEP use across the study period Prevalence ratios (95% Cl) comparing receipt of primary
care between patients who were and were not prescribed
PrEP within each year
Unadjusted P Adjusted P
Influenza vaccination 1.39 (1.31-1.48) <0.001 1.57 (1.47-1.67) <0.001
Tobacco screening 1.15 (1.12-1.19) <0.001 1.13 (1.09-1.16) <0.001
Depression screening 1.34 (1.30-1.38) <0.001 1.18 (1.15-1.22) <0.001
HbA1c or glucose
testing
1.78 (1.70-1.85) <0.001 1.83 (1.75-1.92) <0.001
HbA1c testing 0.98 (0.87-1.11) 0.78 0.89 (0.79-1.01) 0.07
Glucose testing 1.94 (1.85-2.03) <0.001 2.03 (1.93-2.14) <0.001
Prevalence ratios obtained from Poisson models with generalized estimating equations.
Adjusted models included age, gender, year, race/ethnicity, and insurance type, and models for
HbA1c or glucose testing also included diabetes, hypertension, and overweight/obesity.
P<0.001 for all
except HbA1c
Testing

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HIV PrEP Pipeline by Formulation
Systemic Topical – Vaginal Topical – Rectal
Short-
Acting
Tablet
• Oral TDF/FTC daily
• Oral TDF/FTC
2/1/1 (MSM, TGW)
• Oral TAF/FTC
Vaginal Gel
• TFV BAT24 (mITT & post hoc)
• TFV daily (post hoc)
• Griffithsin/carrageenan
• PC-1005
Fast-dissolving film
• TFV film
• Dapivirine film
Fast-dissolving insert
• TFV/FTC insert
• TFV/EVG insert pre-clinical
Rectal Gel®
• TFV
• MVC
• DPV
• IQP-0528
• PC-1005
• Griffithsin/carrageenan
• *potential as lubricant
Douche
• TFV
Fast-dissolving insert
• TFV/EVG
Long-
Acting
Injectable IM
• CAB-LA q2m
Implantable SC
• TAF q12m
• CAB
Infusion IV
• bnAb q2m
Intravaginal ring (IVR)
• Dapivirine
• TFV
• TDF
• MVC
• DPV/MVC
• Pod-IVR TFV/FTC/MVC
• IVR TFV/LNG
32
Key
• Clinical efficacy established
• Clinical trial ongoing/complete
• Clinical trial pending
• Pre-clinical testing
Hendrix, et al. HIV and Women 2018. Boston, MA.

‡
Step 1
Daily oral CAB and
oral TDF/FTC placebo
Daily oral TDF/FTC and
oral CAB placebo
Step 2
CAB injection x 2, 4 weeks apart
then every 8 weeks
plus daily oral TDF/FTC placebo
Placebo injection x 2, 4 weeks apart
then every 8 weeks
plus daily oral TDF/FTC
Step 3
Open-label daily oral TDF/FTC to
cover the PK tail, for up to 48 weeks
CAB
HPTN 083HPTN 083: Efficacy of injectable Cabotegravir
(CAB) for PrEP in MSM and transgender women
TDF/FTC
• N = 4500; Enrolled = 600
• Goals: 10% TGW overall; 50% of US BMSM; 50% overall < 30 year old
• Study duration: 3-5 years
• Sites in North and South America; Asia; SSA (limited)
Primary objective: HIV Incidence
HPTN 084- Efficacy of Injectible Cabotegravir for PrEP in HIV-uninfected
Women Vs TVD. SSA. DB Superiority study. 1:1 Randomization.

‡
Efficacy of Long Acting Cabotegravir in Macaques
Against Repeated Penile SHIV Exposures
PK analysis and penile SHIV challenge of cabotegravir in Rhesus macaques, (N=6)
34
Dobard C, et al. CROI 2018. Boston, MA. Oral #83
• Three monthly IM injections (50
mg/kg) to maintain CAB levels in
plasma above 4x PA-IC90
• Challenge once-weekly (12 weeks);
20 week washout
- SHIV162p3 exposures to
urethra (16 TCID50) and
prepuce pouch (200 TCID50)
• Plasma collected weekly to monitor
CAB levels and SHIV RNA Drug tail
Cabotegravir long acting effectively protects macaques against penile
SHIV infection

DISCOVER: Pivotal Study F/TAF vs TVD for PrEP
 Eligibility: HIV and HBV negative, eGFR ≥60 mL/min, and at least one of the following:
– 2+ episodes condomless anal intercourse (past 12 wks),
– or rectal gonorrhea/chlamydia (past 24 wks)
– or syphilis (past 24 wks)
 Sample size N=5000 to show noninferiority (F/TDF vs F/TAF) assumes 1.4/100 p-y seroconversion rate for
F/TDF arm; 144 seroconversions needed to demonstrate NI
 Sites: sexual health clinics, medical offices (North America, EU)
n=2500
n=2500
Primary Endpoint:
Seroconversion rate/100 p-y
Week 0 9648
F/TAF (200/25 mg) QD
TVD (200/300 mg) QD
72
F/TAF
Switch option
Participants, N
Screened 5,902
Enrolled 5,400
DXA sub-study 373
Adult cis MSM or
TGW
HIV negative

‡
SHIV162p3
FTC/TAF
(-24h)
FTC/TAF
(+2h)
Treated group
(n=6 pigtails)
SHIV162p3
Placebo
(-24h)
Placebo
(+2h)
Control group
(n=6 pigtails)
Repeated once a week during 16 weeks
36
Phase II: Efficacy of FTC/TAF Against Vaginal SHIV Infection
• Pigtailed macaques ( 11.5 years old and 9.0 kg on average)
• Repeated exposures to low (50 TCID50) doses of SHIV162p3
• Design identical to previous studies with FTC/TDF (-24h/+2h modality; 6/6
animals protected; Radzio et al., PLoS One 2012).
• FTC/TAF (20/1.5 mg/kg) administered orally by gavage
• Infection monitored weekly by serology and RT-PCR
Massud I, et al. CROI 2018. Boston, MA. Oral #85.

‡
High Efficacy of FTC/TAF Against Vaginal SHIV Infection
p =0.0422 (Log-rank test)
Efficacy: 82%
Oral FTC/TAF
Placebo controls
0 4 8 12 16
0
50
100
Number of virus exposures
Percentsurvival
37Massud I, et al. CROI 2018. Boston, MA. Oral #85.

‡
Median (range) fmols/106 cells in PBMCs through weeks 1-16 of virus challenges
LOQ: TFV-DP 12 fmol/million, FTC-TP 3 fmol/million
BLQ: below limit of quantification
TFV-DP in PBMC
weeks
fmol/10
6
cells
1 2 3 4 5 6 7 8
1
10
100
1000
10000
14 15
BB0496
BB766
PCG1
BB0550
PBL2
PUG2
median
FTC-TP in PBMC
weeks
fmol/106
cells
1 2 3 4 5 6 7 8
1
10
100
1000
10000
14 15
BB0496
BB766
PCG1
BB0550
PBL2
PUG2
median
38
TFV-DP and FTC-TP Levels During the Virus Challenges
BB0496 BB766 PCG1 BB0550 PBL2 PUG2
FTC-TP TFV-DP FTC-TP TFV-DP FTC-TP TFV-DP FTC-TP TFV-DP FTC-TP TFV-DP FTC-TP TFV-DP
1,255
(388.0-
1,899)
123
(66.9-
167.7)
1,641
(1,386-
2,500)
199
(130.4-
246.5)
1,837
(1,116-
2,127)
237
(195.3-
257.0)
1,499
(1,092-
1,760)
BLQ 2,124
(1,101-
2,748)
829
(339.7-
1,364)
2,653
(2,068-
3,162)
298
(179.1-
370.7)
Massud I, et al. CROI 2018. Boston, MA. Oral #85.

‡
MK-8591-treated animals remain aviremic after
168 days of study
MK-8591 treated animals have a 41.5-fold lower risk of infection (95% C.I. 7.3, 237.9)
P<0.0001 log rank test
Markowitz, M. : Weekly Oral MK-8591 Protects Male Rhesus Macaques against Repeated Low Dose Intrarectal
Challenge with SHIV109CP3. IAS 2017

‡
Low Dose MK-8951 Protects Rhesus Macaques Against
Rectal SHIV Infection
PK analysis and rectal SHIV challenge of MK-8951 in Rhesus macaques, (N=8)
40
Markwoitz M, et al. CROI 2018. Boston, MA. Oral #89LB
MK-8591 remains completely protective at 1.3 and 0.43 mg/kg in
the rhesus macaque intrarectal challenge model.

‡
Broadly neutralizing Antibodies

‡
Efficacy of Broadly Neutralizing Antibodies (BNAbs) in
Macaques Against Repeated Vaginal SHIV Exposures
PK analysis and vaginal SHIV challenge in Rhesus macaques dosed weekly with a single
(3BNC117) or combo (3BNC117 + 10-1074) BNAb injection, (N=12)
42
Garber D, at al. CROI 2018. Boston MA. Oral #82
One subcutaneous administration of 3BNC117 singly, or in combination with 10-1074,
protected macaques against repeated vaginal challenges, supporting the continued
development of these two BNAbs for HIV prevention in women.

‡
TFPD Injectable for Prevention (TIP) Program-UC Berkeley
and RTI
 Controlled release of ARV
for HIV PrEP
– User-independent
– Provider administered
– Discretion of use
 Subcutaneously injected
– Appropriate for women and
men
– Protection from all sexual
routes of exposure
 Biodegradable
 Removable
Gilead confidential and
proprietary-for internal use only
Prototype Thin Film Polymer Devices

‡
Osmotic Pump
• This osmotic flow is directly proportional to the gradient of
concentration of osmolytes in the osmotic chamber.
• The inward H2O flow creates an increased pressure in the osmotic
chamber, which exerts a force on the piston.
• The osmolyte must be included in a supersaturated form, to maintain
its constant concentration of despite the inward flow of H2O

‡
Osmotic Pump

Name Date
NANOCHANNELS:
NO NEED FOR PUMPS!
Diffusion
Free -> Exponential
Constrained:
Constant
Parallel and highly reproducible
industrial microfabrication of
nanochannel membranes
Nanochannel membranes bio-robust structure
with geometrically organized – monodisperse
nanochannels: dimensional tolerances 0.2 nm
Constant drug release achieved with no
pumping mechanism across nanochannels
by leveraging physical and electrostatic
confinement on diffusing drug molecules
Implantable nanochannel delivery systems containing a drug reservoir and mounting a nanochannel membrane as release rate
modulating component (A). In analogy to an hour-glass the implants release their drug constantly until the drug is fully released (B).
Great flexibility of implants and membranes to accommodate any size, shape, release rate for suitable for a variety of clinical
applications (C). Implants allow for transcutaneous reloading of the drug for extended treatments without need for explantation (D).
The implant can include a system that allows for permanently interrupting the drug release ad hoc by using a portable external
A B C D E

Name Date
422LB CROI 2017

‡
GS-CA1 inhibits capsid function at multiple steps
Capsid
Core
Assembly
NUCLEUS
Reverse
Transcription
Nuclear
Translocat
ion
Capsid
Core
Disassem
bly
PRODUC
ER
CELL
Gag-Pol
TARGET CELL
Pre-
integration
complex
NUCLEUS
Integration
Maturatio
n
Gag
GS-
CA1
Matur
e
virion
Defec
tive
virion+GS-
CA1
Confidential

‡
1
10
100
1000
GS-CA1 Pharmacokinetics in Rats
Extended Release Formulation
 Single subcutaneous injection maintains plasma concentrations well
above paEC95 for >10 wks
 Potential for a monthly dosing interval or longer in humans
paEC95 = 11
nM
1 2 3 4 5 6 7 8 9 1
0
0
PlasmaConcentration,nM
Weeks
9x above
paEC95
Confidential

PrEP in 2018 and Beyond

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