Leader in digital CPD
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Professor Linda-Gail Bekker
Director: Desmond Tutu HIV
Centre
Institute of Infectious Disease
and Molecular Medicine
University of Cape Town
The background
incidence of HIV in
South Africa has not
shifted over the last
20 years
This report was made possible
by an unrestricted educational
grant from Cipla. The content
of the report is independent of
the sponsor.
© 2022 deNovo Medica
for Southern African
free CEUs HIV/AIDS
healthcare professionals
Principles of HIV prevention
and the role of PrEP
Learning objectives
You will learn:
• The principles underpinning effective pre-exposure prophylaxis (PrEP) to protect against HIV
infection
• The importance of having PrEP options that are suitable for different populations and needs
• Currently available oral PrEP options, PrEP options that should soon be available, and PrEP
concepts that are currently in development
• The importance of tailored, client-centred treatment and prevention packages that integrate
PrEP with contraception and sexually transmitted infection (STI) services
• Factors that influence persistence or discontinuation of the use of PrEP.
Introduction
The continuing importance of HIV prevention as a key focus in public health is
underscored by the 1.7 million new HIV infections that occurred globally in 2020,
a figure three-fold higher than the UNAIDS target for that year. It has been a
decade since it was learned that antiretroviral-based pre-exposure prophylaxis (PrEP)
provides robust protection against HIV in all populations and routes of infection; to
date, almost one million people have accessed this prevention.
The background incidence of HIV in South Africa has not shifted over the last 20 years.
Every week, 1 500 young women and girls are infected with HIV. What can be done
about this? Professor Linda-Gail Bekker discusses the principles of HIV prevention
and the role of oral PrEP. Alternative and adjunct options for HIV prevention are
currently available or in the pipeline, providing an array of options that are suitable
for all populations.
© iStock/1295052951
JANUARY 2022 I 1
 Principles of HIV prevention and the role of PrEP

Principle 1 – The synergy of prevention and

treatment in the HIV epidemic
When considering the HIV epidemic, it is best and treatment but rather to approach both as
not to take a dichotomous view of prevention synergistic forces.

Treatment as prevention
The triumph of increased access to antiret-
roviral therapy (ART) has averted 12 million
HIV deaths globally. Treatment can provide
secondary prevention in that the HIV infected
individual becomes untransmissible because
their viral load is undetectable.1,2 Treatment
thereby becomes another method in the
arsenal of HIV prevention; however, to be
wholly effective globally, it is necessary to get
all 38 million people who are living with HIV
(PLWH) treated to an undetectable viral load.
Currently, only 67% of PLWH have been
initiated on ART and only 59% are virally
suppressed. Review of five large population-
based studies promulgating ART as HIV
prevention has shown that, unfortunately,
reduction in HIV incidence was modest and
in some cases, did not exist at all (0-30%).3

The power of ART and PrEP

To effectively overcome the HIV epidemic, a
mixture of primary prevention and treatment
“It is the is necessary. Professor Bekker’s view is: “It is
the prevention push and the treatment pull
prevention that are needed together in order to get to a
push and the place where we have zero infections.” Scaling
treatment pull up of access to ART and PrEP is powerful
that are needed
together in U = U: An opportunity to destigmatise HIV
order to get to Improved awareness and branding of the con-
a place where cept of U = U (undetectable equals untrans-
we have zero mittable) is important because it provides an
infections” opportunity to destigmatise HIV, making the
Professor Bekker benefits of testing and of ART more tangible,
present and pleasant.
for population-level reductions in HIV risk,
both among PrEP users and non-users. Using
this approach, San Francisco has seen a 51%
reduction in HIV transmission; other cities
with similar outcomes include London (42%),
Seattle (42%) and Sydney (32%).
A study involving mainly black African men
that looked at the use of U = U messaging to
enhance linkage to care showed that redefin-
ing and reframing the benefits of ART in a
clear and unambiguous message increased
both HIV testing and linkage to care.4

The role of PrEP in partners who are serodiscordant

Using PrEP together with U = U messaging
for partners who are serodiscordant is key to
overcoming:
• Transmission between partners
• Safer conception
• Prevention/eradication of mother-to-child
transmission.

The concept of seroneutral programming is

that regardless of whether one is HIV-positive
or negative, the same service is used by
everyone and that service is person-centred,
attuned, engaged and community-based
(Figure 1).

2 I JANUARY 2022
 Principles of HIV prevention and the role of PrEP

Counseling and testing

HIV negative HIV positive

Link Link

SRHs uptake ART uptake

Contraceptives Contraceptives
Condoms Condoms
PrEP ART
MMC MMC
STI screening STI screening
Harm reduction Harm reduction
SRHs persistence ART persistence

HIV/preg/STI free Viral suppression

Figure 1. Seroneutral programming

Over the
last decade,
innovation Principle 2 – Prevention should be effective and
has given rise tailored
to an array of
To achieve effective control of the HIV epi- for everybody and anybody. Over the last
options for the demic, we need effective primary prevention. decade, innovation has given rise to an array
prevention of Because humanity comes in many shapes and of options for the prevention of HIV trans-
HIV transmission forms, it is ideal to have a prevention option mission (Figure 2).

Harm Treatment
reduction of STIs
Protection Male
and justice circumcision

Microbicides Female
for women condoms

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Male
CPD POINTS prophylaxis
Innovation condoms
+ Lube
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www.denovomedica.com HIV counselling

Post-exposure & testing
and start to earn today!
prophylaxis (PEP)

Behavioural
intervention
(Un)conditional • Abstinence
cash transfers • Be faithful
Treatment for
PMTCT
prevention
Figure 2. Strategies for the primary prevention of HIV transmission

JANUARY 2022 I 3
 Principles of HIV prevention and the role of PrEP

Which oral PrEP options are available today?

Daily oral HIV prevention pills (TDF/FTC)
The first generation of oral PrEP combined daily adherence is high, then HIV prevention
tenofovir (TDF) and emtricitabine (FTC) in is consistent and high (Table 1).5-9
a single pill. Initial studies found that when

Table 1. HIV protection efficacy with daily oral PrEP (TDF/FTC)5-9

HIV protection HIV protection

% of blood samples
Clinical trial efficacy in randomised estimate with high
with TDF detected
People exposed comparison adherence
to HIV via the
Partners PrEP 81% 75% 90%
vaginal mucosa (TDF/FTC arm) (TDF in blood)
need good
daily dosing to TDF2 79% 62% 78%
ensure that they (prescription refill)
are protected
BTS 67% 49% 70-84%
whereas when (TDF in blood/pill count)
exposure is via
the anal mucosa, iPrEx 51% 44% 92%
(TDF in blood)
even four doses
per week are FEM-PrEP & <30% No HIV protection N/A
adequate VOICE

Lessons learned from two clinical trials con-
ducted in Africa, FEM-PrEP and VOICE,
included the observation that women did not
easily take their PrEP, with consequent poor
outcomes for HIV protection. What is since
understood is that people exposed to HIV via
the vaginal mucosa need good daily dosing to
ensure that they are protected, whereas when
exposure is via the anal mucosa, even four
doses per week are adequate.

Can oral PrEP be used on demand?

A study of TDF/FTC on demand versus
placebo on demand in men who have sex with
men (MSM) and transgender individuals
found an 86% relative risk reduction in the
incidence of HIV-1 and a number needed to
treat to avert one HIV infection of 18.10
A smaller study of daily versus on-demand
PrEP in MSM showed that a high preven-
tion efficacy was achieved in both arms
(92%) with coverage of condomless anal
intercourse. The investigators recommended
a flexible approach to individual needs to
maximise prevention efficacy.11

New-generation oral PrEP (F/TAF)

Tenofovir alafenamide (TAF) has better
pharmacokinetics and fewer side effects than
TDF; combined with FTC as oral PrEP,
F/TAF is a smaller pill than TDF/FTC. In
the DISCOVER study, F/TAF achieved non-
inferiority relative to TDF/FTC when used as
daily/on-demand PrEP in the cohort of MSM
and transgender women.12 There is an ongo-
ing efficacy study in women in Africa and it is
anticipated that F/TAF will soon be approved
for use as oral PrEP.

Daily oral PrEP is not feasible for everyone

The need for daily use of oral PrEP can be a PrEP use journey. Data from the SEARCH
barrier to adherence and persistence, and can study indicate that the challenge of adherence
lead to pauses and discontinuations along the is particularly difficult for young people aged

4 I JANUARY 2022
 Principles of HIV prevention and the role of PrEP
15-24 years. With regard to persistence, many
young women in the POWER study wanted
to take up oral PrEP but there was quite a
Behavioural biases influencing poor adherence
Although most people intend to do well,
struggles with motivation are influenced
by numerous behavioural biases that affect
adherence. Status quo bias, loss aversion and
overconfidence may affect adherence, as can
giving in to temptations at the expense of
long-term goals (myopia).
People make the best decisions when they
get good feedback about results of healthy
behaviour and when the benefits of an action
are easy to observe; furthermore, the decision
needs to be easy to make. In the context of
There was an PrEP, the benefits of HIV prevention are gen-
89% reduction erally largely invisible, and it is important that
in HIV infection
in sub-Saharan PrEP options coming soon
African
women using Dapivirine ring
cabotegravir The dapivirine vaginal ring for HIV pre-
compared to vention is already available in five African
those using FTC/ countries, including South Africa. Two large
randomised controlled trials (RCTs) and
TDF, although real-world efficacy data show a 50% risk
both agents reduction;18,19 the World Health Organization
were used with guidelines recommend the dapivirine ring as
good effect a second option in low- and middle-income
countries if oral PrEP cannot be accessed.
Cabotegravir LA
Cabotegravir is awaiting approval from
the Food and Drug Administration for use
as both an ART agent and a PrEP agent.
Due to its very long half-life, a single injec-
tion is administered every eight weeks. A
randomised, double-blind, double-dummy
trial20 has shown both non-inferiority and
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Islatravir monthly pill
Islatravir is a translocation inhibitor with a
novel mechanism of action; it is very potent
with an extraordinarily long half-life. It is
being developed for both treatment and
significant fall-off over time. Similar trends
are seen in studies of MSM and transgender
women cohorts.13-17
prevention options are available, affordable,
simple to administer and easy to adhere to.
Professor Bekker postulates: “The solution
to this may be that we need less frequent and
alternative dosing, and longer-acting agents
in different formulations.”
Long-acting injectable PrEP agents would
offer the benefit not only of improved adher-
ence, but also of earlier detection of non-
adherence. Non-adherence to oral therapies
can go undetected for a long time, whereas
the health care provider is more quickly aware
that a patient is off treatment if they do not
return for their injection.
REACH, a cross-over RCT, compared the
dapivirine ring and oral FTC/TDF PrEP;
both arms performed quite well in respect of
adherence. However, better rates of full com-
pliance were observed with the dapivirine ring
and, given the choice, more women prefer the
vaginal ring to oral PrEP.
superiority of cabotegravir to FTC/TDF
when used as PrEP. There was an 89% reduc-
tion in HIV infection in sub-Saharan African
women using cabotegravir compared to those
using FTC/TDF, although both agents were
used with good effect to show an overall
reduction across the whole cohort.
antibody threshold bridging approach will
soon be underway.
prevention in the form of both a monthly pill
and an implant for prevention. Phase 3 clini-
cal trials are currently underway.21.22
JANUARY 2022 I 5
 Principles of HIV prevention and the role of PrEP

Lenacapavir LA injectable

Lenacapavir, an HIV-1 capsid inhibitor, is be conducted in South Africa and Uganda,

a single injection administered every six and another study is underway in MSM,
months.23 A study on the use of lenacapavir transgender and non-binary people.
in adolescent girls and young women will

A high STI
Looking to the future
burden among The future is rich with possibilities for com-
bining formulations and active ingredients
individuals that are fit for purpose and suited to varying
initiating PrEP personal choices. PrEP concepts in develop-
and among ment include the use of microneedles as part
persistent of topical introduction of antiviral agents,
PrEP users fast-dissolving vaginal and rectal inserts,
underscores the
opportunity to Principle 3 – Prevention should be integrated
integrate PrEP
programmes Even though there are now tools to control
with STI services the HIV epidemic, if STIs are not addressed,
their spread will accelerate and lead to wide-
spread morbidity, complicating and compro-
mising efforts to control the HIV epidemic. A
high STI burden among individuals initiat-
ing PrEP and among persistent PrEP users
underscores the opportunity to integrate
PrEP programmes with STI services.24,25
Tailored, client-centred treatment and
vaginal films, and the use of microbicide gel
as lube. Multipurpose prevention technolo-
gies combine treatment for sexually transmit-
ted infections (STIs), contraception and HIV
prevention modalities. Work on a vaccine
continues.
prevention packages that are appropriate for
adolescent girls and young women, MSM and
transgender people, people who inject drugs,
and for sex workers will place emphasis on
different elements of holistic care. In light of
the specific needs of different populations,
multipurpose prevention technologies add
convenience. The Quatro study found that
86% of the cohort would prefer a 2-in-1 prod-
uct to prevent both HIV and pregnancy.26

Principle 4 – Prevention services should

accommodate preference/choice
PrEP prevention services should always
accommodate individual preferences.
Differentiated service delivery is a person-
centred approach that adapts HIV services
across the cascade of HIV care and preven-
tion, reflecting the preferences and expecta-
tions of various groups of PLWH and those
at risk of infection.
PrEP delivery models and distribution points
can be reconsidered (Figure 3) in order to
facilitate access to those cycling in and out of
the PrEP care cascade (Figure 4). Prevention
preferences may be impacted by changes in
career or in relationship status, new relation-
ships, living circumstances and travel. Drivers
of persistence with regard to the use of oral
PrEP include self-efficacy, STI diagnosis and
condomless anal intercourse. Reasons for
discontinuation include:
• Not currently at risk for HIV
• Logistical problems with access
• Intolerable side effects
• Positive HIV test
• Dislike of taking pills.

Prevention preferences may be

impacted by changes in career or in
relationship status, new relationships,
living circumstances and travel

6 I JANUARY 2022
 Principles of HIV prevention and the role of PrEP

Figure 3. PrEP delivery models and distribution points

Eligible
Awareness
Willingness
Access
Uptake

… self-
… is HIV … knows identifies as … has a PrEP … receives a Effective
Persistence
negative and about PrEP & a good PrEP provider, and prescription use
at high risk for whether they candidate and is able to and begins
HIV infection are eligible wants to take afford PrEP taking PrEP
PrEP

Cycling on/off:
• Need
• Convenience

Figure 4. The PrEP care cascade

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Differentiated service delivery is accessible, health support. Commonly, the attitudes
layered and integrated care (Figure 5). Many of health care workers do not embrace the
individuals experience anxiety or fear in patient’s needs; community empowerment
accessing health care at government facili- and other peer engagement programmes have
ties. Most display a keen enthusiasm for more been proven to reduce stigma, discrimination
contact and education, and there is also an and marginalisation, and need to be brought
enormous need for psychosocial and mental to scale and included in health clinics.

JANUARY 2022 I 7
 Principles of HIV prevention and the role of PrEP

IDU MSM SW AGYW YM

PrEP, Social protection, GBV

PrEP, Protection, GBV
PEP, PrEP, Lube
N/S/OSD, PrEP

PrEP, MMC
Informed, non-prejudicial health clinics

Community support and programming

ARV treatment and access

Male/female condom distribution

HIV testing and counselling

Tailored comprehensive information

Stigma and discrimination reduction

Social justice/Human rights/Legal framework

Figure 5. Differentiated service delivery

Key learnings
• While ART can provide secondary prevention of HIV infection, the effect is modest; a mix of primary
prevention and ART is necessary to overcome the HIV epidemic

• Innovation has given rise to many different strategies for the primary prevention of HIV transmission

• Currently available oral PrEP options include TDF/FTC and F/TAF; efficacy of daily versus on-demand use is
influenced by the route of exposure

• Daily oral PrEP is not feasible for everyone; PrEP options that should be available soon include the
dapivirine ring, cabotegravir LA, islatravir and lenacapavir LA.

• PrEP prevention services should always accommodate individual preferences.

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This CPD-accredited programme was
written for deNovo Medica by
Glenda Hardy
BSc(Hons) Medical Cell Biology
Principles of HIV prevention and the role of PrEP
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Click on reference to access the scientific article
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