Health in Action
Early Experiences Implementing Pre-exposure
Prophylaxis (PrEP) for HIV Prevention in San Francisco
Albert Liu1,2*, Stephanie Cohen2,3, Stephen Follansbee4, Deborah Cohan5, Shannon Weber6,
Darpun Sachdev1,2, Susan Buchbinder1,2,7
1Bridge HIV, San Francisco Department of Public Health, San Francisco, California, United States of America, 2Department of Medicine, University of California, San
Francisco, San Francisco, California, United States of America, 3STD Prevention and Control, San Francisco Department of Public Health, San Francisco, California, United
States of America, 4Kaiser Permanente Medical Center, San Francisco, California, United States of America, 5Department of Obstetrics, Gynecology, and Reproductive
Sciences, University of California, San Francisco, San Francisco, California, United States of America, 6Department of Family and Community Medicine, University of
California, San Francisco, San Francisco, California, United States of America, 7Department of Epidemiology and Biostatistics, University of California, San Francisco, San
Francisco, California, United States of America
PrEP: Opportunities and
In July 2012, more than 30 years after
the initial HIV case reports, the United
States (US) Food and Drug Administration
(FDA) approved the first drug for the
prevention of sexually acquired HIV
infection. On the basis of compelling safety
and efficacy data from pre-exposure pro-
phylaxis (PrEP) trials of men who have sex
with men (MSM) conducted across four
continents and serodifferent heterosexual
couples and young men and women in
sub-Saharan Africa [1–3], the FDA issued
the landmark approval of once-daily, co-
formulated emtricitabine/tenofovir (FTC/
TDF) for HIV prevention in men and
women at risk for acquiring HIV infection
through sexual exposure. Another recent
trial showed PrEP was safe and efficacious
in injection drug users in Thailand .
PrEP trial results highlight the critical
relationship between adherence and effi-
cacy , the lack of risk compensation in
blinded PrEP trials [2,6,7], and the
importance of ensuring individuals are
HIV-negative prior to initiating PrEP to
minimize HIV resistance . Further-
more, modeling studies suggest PrEP can
be a cost-effective HIV prevention strate-
gy, particularly if targeted to the highest
risk populations [9–11].
Although the FDA approval marks an
important milestone in HIV prevention,
several factors, including negative results
from two recently completed PrEP trials
among women in Africa [12,13]; per-
ceived low demand for PrEP [14–17]; and
The Health in Action section is a forum for
individuals or organizations to highlight their
innovative approaches to a particular health prob-
Citation: Liu A, Cohen S, Follansbee S, Cohan D, Weber S, et al. (2014) Early Experiences Implementing Pre-
exposure Prophylaxis (PrEP) for HIV Prevention in San Francisco. PLoS Med 11(3): e1001613. doi:10.1371/
Published March 4, 2014
Copyright: ? 2014 Liu et al. This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original author and source are credited.
Funding: AL, SC, and SB received funding from the National Institutes of Allergy and Infectious Diseases (UM1
AI069496) for conduct of the Demo Project. Study drug was supplied by Gilead Sciences for The Demo Project.
The funders of the Demo Project had no role in the preparation of this manuscript. The funders had no role in
study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views
expressed herein do not necessarily reflect the official policies of the City and County of San Francisco; nor does
mention of the San Francisco Department of Public Health imply its endorsement. The contents of this
publication are solely the responsibility of the authors and do not necessarily represent the official views of the
Competing Interests: The only competing interest for Drs. Liu and Buchbinder is that they receive NIH grant
funding for studies related to PrEP, including the demonstration project that is described in the paper.
However, they receive no money from the pharmaceutical (Gilead) that makes PrEP, nor is NIH funding
contingent upon receiving any specific results from that study.
* E-mail: email@example.com
Provenance: Not commissioned; externally peer reviewed
N Pre-exposure prophylaxis (PrEP) has been demonstrated to be safe and
efficacious in clinical trials and emtricitabine/tenofovir was approved by the
United States Food and Drug Administration for use as PrEP in 2012.
N We report early experiences with PrEP uptake and delivery in three different
settings in San Francisco: a PrEP demonstration project in a municipal sexually
transmitted diseases (STD) clinic, and two PrEP delivery programs (a private
health maintenance organization and an HIV-specific reproductive health
N Interest in PrEP is high in San Francisco, particularly among men who have sex
with men attending the STD clinic, and it is feasible to incorporate PrEP into
busy clinical settings. Key next steps for PrEP implementation include increasing
PrEP knowledge; expanding PrEP access; combating PrEP stigma; and
optimizing interventions to promote PrEP uptake and adherence while
reinforcing risk reduction strategies.
N PrEP can be an important component of a comprehensive HIV prevention
program and complement efforts to increase HIV testing, linkage to care, and
early initiation of antiretroviral therapy.
PLOS Medicine | www.plosmedicine.org1March 2014 | Volume 11 | Issue 3 | e1001613
concerns about drug adherence ,
spread of antiretroviral resistance ,
medication diversion , risk compensa-
tion , and cost  have led to debate
on whether and how PrEP should be
implemented [23–30]. The World Health
Organization has issued guidance recom-
mending PrEP demonstration projects be
conducted to address these important
issues and help determine how PrEP may
best be scaled up in different settings to
maximize public health impact , and a
number of PrEP demonstration projects
and roll-out programs are being planned
or are underway . We describe early
experiences with PrEP uptake and delivery
in the first year of PrEP implementation
post-FDA approval in three different
settings in San Francisco, California: an
NIH-funded PrEP demonstration project
in a municipal STD clinic and two PrEP
delivery programs (a managed care orga-
nization and a HIV-specific reproductive
health clinic). We also propose next steps
for the prevention field based on insights
learned from our early experiences with
Moving from Efficacy to
On the basis of promising efficacy data
from PrEP trials, programs to evaluate
PrEP delivery launched in San Francisco,
a metropolitan area heavily impacted by
HIV, with an HIV prevalence of 23%
among MSM  and an estimated
incidence of 782 cases/100,000 MSM
(95% CI 505–1,058) in 2011 . These
programs are directly assessing concerns
about uptake, adherence, resistance, and
risk compensation, as well as models of
PrEP delivery in different settings. We
describe the core components of these
varied programs (see Table 1), present
preliminary data on PrEP uptake in these
three programs, and summarize lessons
learned to date.
PrEP in an STD clinic
San Francisco City Clinic (SFCC), the
city’s municipal STD clinic, offers a range
of sexual health services, including HIV
and STD screening, diagnosis and treat-
(PEP), family planning, and emergency
contraception. In 2011, the clinic conduct-
ed approximately 19,000 visits with 12,000
patients, of whom 38% were MSM and
1% transgender. HIV incidence among
MSM at SFCC is high, with a 2.3%
annual seroconversion rate . In Octo-
ber 2012, SFCC began offering PrEP to
MSM and transgender women through
The Demo Project, a one-year National
Institutes of Allergy and Infectious Diseas-
es-funded PrEP demonstration project
From September 2012–2013, 571 indi-
viduals have been evaluated at SFCC for
PrEP, and 261 participants have enrolled
in The Demo Project, for an overall
uptake of 49% among potentially eligible
Table 1. Core components of PrEP delivery programs in San Francisco.
Assess patient as PrEP candidate
On the basis of local epidemiology, determine risk criteria for delivery of PrEP
Assess for HIV risk at baseline and all follow-up visits
Provide information about risks and benefits of FTC/TDF for PrEP as well as other HIV prevention options
Assess client’s interest in starting or continuing PrEP at each visit
Assessment for symptoms of acute
Assess for acute HIV symptoms at baseline and all follow-up visits.
If symptoms concerning for acute HIV, order an individual HIV viral load.
Defer initiation of PrEP until acute infection ruled out.
Perform HIV testing at baseline and all follow-up visits, at least every 3 months.
Confirm HIV test is negative immediately before dispensing PrEP.
If available, test for acute HIV infection (using 4th generation Ag/Ab test, or pooled/individual HIV RNA) prior to PrEP
initiation and at all visits when symptoms of acute HIV infection are reported.
Consider obtaining 4th generation HIV Ag/Ab test at all follow-up visits (window period considerably narrower than current
rapid HIV tests).
STD screening (without symptoms)
For MSM and trans women: syphilis, NAAT-based gonorrhea and chlamydia screening from urine, rectum, and pharynx at
baseline and every 3 months or at each encounter for HIV testing
For women: NAAT based gonorrhea and chlamydia screening from vaginal swab (or urine) at baseline and every 6 months
No consensus guidelines exist on optimal frequency or method of kidney function monitoring for patients using FTC/TDF for
PrEP (see Table S1).
FTC/TDF should not be dispensed for PrEP if patient has CrCl ,60.
Hepatitis B virus (HBV) screen
At minimum, check hepatitis B surface antigen (HBSAg) at baseline.
If no history of prior vaccination or HBV susceptible, offer HBV vaccine.
If chronically infected, monitor liver function tests closely when stopping FTC/TDF, and consider appropriate medication for
Reproductive health assessment
Conduct pregnancy test at baseline and at each follow-up visit.
Evaluate if women are planning to become pregnant, or breast-feeding.
If pregnant, discuss risks/benefits of continuing PrEP with a prenatal provider.
If breastfeeding, discuss risks/benefits of PrEP and continued breastfeeding.
counseling, side effect management
Baseline and all follow-up visits.
Optimal strategy for delivering counseling unclear. Counseling approaches for PrEP programs in San Francisco are described
in Table S1.
Management of HIV seroconversion
Patients taking PrEP who have a positive HIV test should be instructed to stop PrEP immediately and be offered post-test
counseling and HIV partner services.
Send HIV viral load and genotype and link patient to HIV primary care and treatment in an expedited fashion.
Ag/Ab, antigen/antibody; CrCl, creatinine clearance; FTC/TDF, emtricitabine/tenofovir; MSM, men who have sex with men; NAAT, nucleic-acid amplification test; PrEP,
pre-exposure prophylaxis; STD, sexually transmitted disease.
PrEP Implementation in San Francisco
PLOS Medicine | www.plosmedicine.org 2March 2014 | Volume 11 | Issue 3 | e1001613
clients (Table 2). The most common
reasons for declining PrEP include not
enough time for study participation (28%),
side effect concerns (25%), and no per-
ceived HIV risk (8%). PrEP uptake
prior knowledge about PrEP and those
reporting higher risk behaviors. Demand
for PrEP has exceeded clinic capacity,
with a wait-list of several dozen clients. To
date, overall study retention is high;
approximately 8% of participants have
discontinued PrEP (Table 3). Several
participants have expressed anxiety about
PrEP access after completing their one-
year participation in this project. Project
staff are identifying sources of PrEP in the
community, linking participants to pre-
vention and care upon project completion.
PrEP-related stigma (participants feeling
stigmatized by others regarding their
decision to use PrEP) has deterred some
clients from accessing PrEP. Participants
in the Demo Project are asked quarterly
about social harms related to study
participation. Fifteen of 20 social harms
reported to date were related to PrEP
stigma. Participants reported stigma from
peers, who believe that PrEP will lead to
increased risk-taking behavior and may
divert resources away from HIV-positive
people, and medical providers, who are
unwilling to prescribe them PrEP or
appear judgmental about their decision
to use PrEP.
PrEP in a health maintenance
Kaiser Permanente Health Plan pro-
vides comprehensive primary and special-
ty medical care to over 185,000 members
in San Francisco. More than 2,500 HIV-
positive adults receive care through Kai-
ser’s HIV Care and Prevention Program.
Health plan members have a broad
spectrum of payor sources for access to
Kaiser insurance, including employer-
based programs, Medi-Cal, and Healthy
San Francisco (a health access program for
low income residents of San Francisco)
. In May 2012, a PrEP program was
initiated in conjunction with other routine
HIV prevention strategies (Table S1).
Although HIV medication prescribing is
restricted to HIV specialists, all adult
primary care providers are encouraged to
refer interested individuals to the HIV
program coordinators, either a pharmacist
or nurse, for possible initiation of PrEP.
While the number of patients who discuss
PrEP with their providers and decide not
to pursue a referral is not systematically
captured, informal discussions with pro-
viders with large panels of MSM suggest
that for every person referred, one to three
members declined referral after a discus-
sion about PrEP with their provider.
Since the launch of the Kaiser’s PrEP
program in San Francisco in April 2012,
more than half of the 123 men and women
referred by both HIV-specialty providers
(65%) and non-HIV-specialty providers
(35%) have initiated PrEP (table 2). Most
common reasons for declining PrEP in-
clude decision to use PEP (47%), failure to
respond to intake request or initial lab
testing (28%), and underlying medical
conditions (11%). Of those started, ap-
FTC/TDF due to a variety of reasons
PrEP in an HIV-specific reproductive
Bay Area Perinatal AIDS Center (BA-
PAC) is a program of the University
of California San Francisco, providing
ment and prenatal care to HIV-positive
women and HIV-negative women with
HIV-positive male partners (Table S1).
BAPAC manages approximately ten to 15
HIV-positive pregnant women and pro-
vides preconception counseling for eight to
ten patients per year. Potential candidates
for PrEP are referred to BAPAC by
local providers or are self-referred for
consultation on lowering HIV transmis-
sion risk during conception and pregnan-
cy. In 2010, BAPAC began offering PrEP
to HIV-negative pregnant women who
were having sex without a condom with
HIV-positive male partners. In 2012,
BAPAC expanded the PrEP program to
include HIV-uninfected women seeking
safer conception options with their HIV-
infected male partners. BAPAC has also
recently launched the PRO-Men initiative
to educate HIV-positive men who have
sex with women about their reproductive
options and provide preventive services to
their HIV-negative female partners, in-
cluding PrEP. BAPAC provides care for
women through six weeks post partum,
when women transition to a primary care
provider who can continue to prescribe
PrEP as needed.
Since 2010, 15 HIV-negative women
with HIV-infected male partners have
been screened as part of comprehensive
HIV prevention counseling at BAPAC for
PrEP eligibility. Seven of these women
initiated PrEP during prenatal or precon-
ception care, one of whom stopped PrEP
after a few days due to nausea and low risk
perception given her partner’s long term
viral suppression. Reasons for not initiat-
ing PrEP included lack of insurance
coverage, and a combination of low risk
perception, concerns about risks to them-
selves or their babies, and cessation of risk
While only a few women have initiated
PrEP at BAPAC thus far, data suggest
HIV-serodifferent couples in the US want
Table 2. PrEP uptake and follow-up in three PrEP delivery programs in San Francisco.
PrEP Uptake Cascade and Follow-up
Date Began Offering PrEP
September 2012 April 2012January 2010
n referred/assessed for eligibility 57112315
n potentially eligible531 118 11
n initiated PrEP261 707
n person-months of follow-up 1,58537024
Average duration (months) of follow-up (range) 6.0 (0.3–11.7) 5.3 (0.5–16)3.4 (1–7)
Data through September 2013.
aIncludes medical and behavioral eligibility and program eligibility based on health insurance coverage.
PrEP Implementation in San Francisco
PLOS Medicine | www.plosmedicine.org3March 2014 | Volume 11 | Issue 3 | e1001613
to incorporate PrEP as a safer conception
option. Between 2006 and 2011, the
National Perinatal HIV Hotline and
Clinicians’ Network took 152 calls regard-
ing conception for serodifferent couples;
the volume of calls has increased over
time, from ten calls in 2006 to 43 in 2011
. Thirty-four percent of callers sought
advice specifically on alternative safer
conception interventions such as timed
intercourse and PrEP.
Key Lessons Learned
Lessons learned from three San Fran-
cisco PrEP programs can inform future
PrEP rollout. First, accurate consumer
knowledge about PrEP is a critical first
step in PrEP implementation, and prior
PrEP awareness was associated with in-
creased uptake in the STD clinic setting.
Second, across all three programs, patient
risk perception and concern about side
effects appear to play an important role in
PrEP uptake, adherence, and persistence
(continuing PrEP over time) and will need
to be addressed to optimize PrEP targeting
and implementation. Third, ensuring ad-
equate clinic capacity and sustainable
delivery of PrEP is critical to addressing
ongoing high demand for PrEP. For time-
limited PrEP programs (e.g., Demo Proj-
ect and BAPAC), it is important to create
linkage to ongoing PrEP access after
program completion. While this may be
a lesser concern for PrEP programs
embedded within existing clinical systems
(e.g., Kaiser), insurance coverage for PrEP
is an important consideration in determin-
ing ongoing PrEP access across all pro-
grams. Finally, PrEP stigma can pose a
barrier to uptake and retention and will
need to be addressed among both provid-
ers and communities to maximize the
impact of PrEP.
Next Steps for PrEP
On the basis of these lessons learned, we
have identified priority next steps to
address emerging delivery issues and to
maximize PrEP’s public health impact.
While the examples provided focused on
PrEP implementation in the US, several of
these concepts and principles may be
generalizable to PrEP delivery outside of
Increase PrEP knowledge
Increasing PrEP knowledge among po-
tential PrEP users is a keystep to facilitating
PrEP implementation . Community
awareness of PrEP appears to be increasing
in San Francisco, with PrEP awareness
increasing from 20% in 2006  to 44%
in 2011 in community-based surveys (Ray-
mond H Fisher, personal communication,
September 27, 2013). Increasing PrEP
awareness is likely due in part to a range
of community engagement activities con-
ducted in collaboration with community
partners. For example, co-incident with the
initiation of the Demo Project, the San
Francisco AIDS Foundation launched a
broad PrEP education campaign, including
ads on billboards and in transit stations and
an informational website (prepfacts.org).
Several well-attended public discussion
forums were also held in the community.
PrEP knowledge among individuals at-risk
for HIV has been limited across the US
 but appears to be slowly increasing
after release of iPrEx results [17,41]. In
recent surveys of PrEP knowledge, PrEP
awareness ranged from 19% in an online
sample of US MSM  to 63% among
serodifferent couples in San Francisco .
Another challenge is that individuals who
could benefit from PrEP are often not
engaged in care. Collaboration with com-
munity partners outside of clinic settings
will be critical to reaching at-risk popula-
tions, providing PrEP education, and
facilitating linkages to PrEP providers .
Expand PrEP access
As interest in PrEP among high ser-
oincidence populations continues to rise in
San Francisco, additional PrEP delivery
sites in the community are needed.
Increasing access to PrEP requires ensur-
ing patients have affordable access to
FTC/TDF. Some commercial private
insurers are providing coverage for PrEP,
although co-pays vary by plan, and some
insurers may require prior authorization
. The rapidly changing health insur-
ance marketplace, including implementa-
tionof the Affordable
may change PrEP access in as yet
unknown ways. Currently, Gilead pro-
vides uninsured patients access to FTC/
TDF through their medication assistance
Developing a cadre of skilled providers
will also be essential to scaling up PrEP
. Many individuals do not feel com-
fortable discussing risk behaviors with
their providers [45,46], and many provid-
ers do not initiate discussion about HIV
risk with their patients [47–49]. Providers
may not have experience prescribing or
monitoring patients taking FTC/TDF.
Increasing PrEP knowledge among health
care providers and identifying and training
community providers who are skilled in
taking sexual histories and prepared to
offer PrEP as part of a comprehensive
prevention package will be critical to
expanding PrEP access.
PrEP delivery systems will also need to
accommodate the increased visit volume
associated with scaling up comprehensive
PrEP services. PrEP delivery is feasible,
but requires staff, time, space, and exper-
tise. A range of models for PrEP delivery
Table 3. Reasons for discontinuing PrEP across three PrEP delivery programs in San Francisco.
Reason Overall N
Decreased risk perception9
Experienced side effects/toxicity8
Difficulty with medication adherence/monitoring requirements5
Leaving health plan4
Concerns about long term side effects3
Worsening of underlying medical condition1
Lack of time1
PrEP Implementation in San Francisco
PLOS Medicine | www.plosmedicine.org4 March 2014 | Volume 11 | Issue 3 | e1001613
clinics , primary care clinics ,
and community-based organizations with
co-located or linkage to clinical services
, although each of these settings may
face unique challenges in PrEP delivery.
For example, while STD clinics serve a
population at-risk for HIV infection, most
operate on a drop-in or urgent care basis
and do not have established systems for
providing continuity care or ongoing
monitoring (e.g., creatinine testing). Con-
versely, primary care clinics are experi-
enced with continuity care, but will
require approaches to identify patients
eligible for PrEP and deliver risk reduction
and adherence counseling . Solutions
to these issues may be addressed by
leveraging existing resources to provide
PrEP services, including cross-training of
staff (e.g., health educators, pharmacists,
nurses) to deliver PrEP counseling .
Similar to the movement away from ‘‘HIV
exceptionalism’’ and integration of routine
HIV testing into primary care settings
[53,54], PrEP delivery will require inte-
gration into primary care settings to
maximize PrEP coverage of at-risk indi-
viduals. Experience and lessons learned
from PrEP implementation programs in
more specialized settings (e.g., STD/HIV
clinics) can be used to develop user-
friendly tools (e.g., patient education and
counseling materials, checklists for PrEP
prescribing) to facilitate primary care
providers delivering PrEP in their practic-
been proposed, includingSTD
Optimize PrEP support
Promoting accurate risk perception and
information about potential FTC/TDF
side effects and strategies to cope with
them will be critical to successful PrEP
implementation. Risk assessment tools are
currently being developed and validated
[55,56], and several PrEP demonstration
projects are evaluating strategies such as
text messaging to support adherence and
promote retention . Other programs
are evaluating the role of real-time phar-
macokinetic testing to monitor adherence
and trigger enhanced adherence interven-
tions. In The Demo Project, we have
developed a one-page handout called
‘‘PrEP Basics,’’ which provides anticipato-
ry guidance regarding PrEP use (see Text
Combat PrEP stigma
Participants in the Demo Project and
other PrEP studies have reported feeling
stigmatized by their decision to use PrEP
by medical providers, friends, and sex
partners. HIV-related stigma and discrim-
ination have a profoundly negative impact
on people living with and at risk for HIV
, acting as deterrents to HIV-testing,
serostatus disclosure, and linkage and
retention in care . Likewise, PrEP-
related stigma could act as an important
barrier to PrEP uptake and dissemination.
Combating PrEP stigma will require a
multi-faceted approach, including social-
marketing campaigns, education for health
care providers, and a broad recognition of
PrEP users as individuals proactively using
proven prevention strategies.
As the PrEP and HIV prevention fields
evolve, several key questions will need to
be addressed to optimize PrEP delivery.
These issues include determining the
optimal target populations for PrEP,
standardizing guidelines for initiating and
discontinuing PrEP, and evaluating cost-
effectiveness. Our early experience with
PrEP in San Francisco has illustrated that
interest in PrEP is high among populations
at risk for HIV infection, and PrEP can be
incorporated into busy clinical settings.
We believe PrEP can be an important
component of comprehensive HIV pre-
vention programs that include efforts to
improve HIV testing, linkage to care, and
early initiation of antiretroviral therapy.
delivery systems in San Francisco.
Characteristics of PrEP
We would like to thank all the study participants
who participated in the Demo Project, Kerry
Murphy, NP and Sally Grant (Bridge HIV, San
Francisco Department of Public Health) for
input in designing the PrEP Basics Handout
(Text S1), and Henry Fisher-Raymond for
sharing data on PrEP awareness from the
National HIV Behavioral Surveillance survey
conducted in San Francisco.
Conceived and designed the experiments: AL
SC SF DC SW DS SB. Performed the
experiments: AL SC SF DC SW SB. Analyzed
the data: AL SC SF DC SW DS SB. Wrote the
first draft of the manuscript: AL SC SF DC DS
SB. Contributed to the writing of the manu-
script: AL SC SF DC SW DS SB. ICMJE
criteria for authorship read and met: AL SC SF
DC SW DS SB. Agree with manuscript results
and conclusions: AL SC SF DC SW DS SB.
Enrolled patients: AL SC SF DC SB.
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PrEP Implementation in San Francisco
PLOS Medicine | www.plosmedicine.org6March 2014 | Volume 11 | Issue 3 | e1001613