1. Safety. This
should be the first consideration in any medical intervention. It was for
obvious reasons a worry with a surgical procedure like circumcision. But
although tenofovir and emtricitabine, the drugs currently used as PrEP, have
years of safety data behind them, as programmes expand, rare events such as
kidney failure will happen. Comprehensive
and reliable reporting systems need to be in place for these rare events. An example
of an adverse event in VMMC that should have been reported earlier was one of
two cases of tetanus infections that went unreported in 2012. They were only
uncovered when a larger cluster of tetanus cases occurred in 2014.

The authors also suggest that drug resistance caused by people
taking PrEP while in acute HIV infection should be reported as an adverse
event, especially as this impacts on future treatment in
settings where second- and third-line therapies may be harder to access. They
do however emphasise that modelling studies suggest that PrEP use will contribute to
less than 5% of the global burden of HIV drug resistance.

2. Engaging
communities and governments.
PrEP has only been adopted with enthusiasm by
a few countries and many others continue to treat it with caution. Both VMMC
and PrEP are controversial interventions or have a history of being so. It is
notable that in countries where PrEP has been adopted, it has benefitted from local
champions ranging from parliamentarians in Zimbabwe to traditional leaders in
Zambia – and, one might add, supportive physicians and researchers.

3. Demand creation. One
lesson from the rollout of VMMC is that it initially appeared that there was a
high demand for it, due to uptake by men who had already heard about VMMC and
wanted it. However, this relatively small pool of early adopters soon dried up,
leaving clinics under-utilised. The authors advise that for PrEP to reach as
many people as need it, innovative demand-creation campaigns should be
introduced early to ensure they also want it. The authors argue that if
demand-creation campaigns had started in the US earlier, PrEP uptake would have
been faster. Even now, PrEP coverage amongst those in highest need is estimated
at 30%, with much lower rates in young and ethnic-minority MSM and in women. In high-prevalence countries, PrEP awareness remains very limited.

4. PrEP delivery. “Service
delivery points need to be as varied as the populations they serve,” the
authors write. The provision of HIV services
in a wide variety of settings has long been a bone of contention when it comes
to HIV testing, with
testing expanding slowly from being administered by physicians in clinics, to nurse
and trained volunteers in community clinics, and now self-testing. The authors
say that even a surgical intervention like VMMC can be delivered in
innovative ways such as in tents or retrofitted buildings, and by task-shifting
from doctors to nurses and
even volunteers
. PrEP is much easier to provide in a variety of settings,
and it is the HIV testing and kidney monitoring that may need imaginative delivery
methods.

Another measure that has proved useful in circumcision,
especially in spreading interest locally, is to introduce mobile, temporary circumcision
clinics in different areas. While PrEP needs ongoing clinical support, the same
methods could be used to generate interest. Clinics outside work hours are also
important, not just to reach working men but also adolescents at school.

5. Supply chains. While
supply chains for antiretroviral drugs are well-established – though in some
places still susceptible to stockouts – it is the monitoring tests that, again, will
need innovative supply chains. Tests formerly only administered by doctors including
creatinine (for kidney function) and hepatitis B serology may need to be
delivered in non-clinical settings.

6. Cost-effectiveness
models.
The authors say that cost-effectiveness models – which should be
continually refined as new data arrives – have been a vital part of making the
case for VMMC and will continue to be for PrEP. Because of this, work needs to
be put into framing them in different ways for different audiences. They comment
that “health policy leaders as well as economists” need to be able “to readily appreciate
the substantial benefits” of both VMMC and PrEP. For instance, refining one
model down to the single statement that nine circumcision procedures would be
needed to stop one HIV infection over one decade proved to be helpful in
convincing politicians.

Cost-effectiveness models for PrEP need to be developed that
include the ‘collateral benefits’ of PrEP such as increased rates of HIV
testing and diagnosis. They should also have geographical sensitivity so that
they can track changes in risk in particular areas or groups.

7. Sustainability. A
major topic at the International AIDS Conference this year was the
sustainability of HIV funding
in a world where global HIV financing initiatives
are increasingly leaving the funding of treatment to national governments. This
is still a problematic and slow-moving area in the field of HIV prevention and
few VMMC programmes have reached the level of maturity that would imply
sustained support via national health services. PrEP’s initial outlay cost is
probably lower than VMMC but the question of its sustainability is clearly even
more crucial. One way to ensure its continued sustainability is to make sure it
is integrated into existing, routine adult and adolescent healthcare settings
such as STI, family planning and school clinics.

8. Advances in
technology.
New ways of supplying biomedical HIV prevention are
currently being developed including injectables and vaginal
rings. It is important, say the authors, both to hasten the development of interventions
that may circumvent the difficulties oral PrEP has with retention and
adherence, but also to recognise that they may come with their own problems. An
example from VMMC is that a couple of new devices (the Shang Ring and PrePex) were
promoted and adopted in circumcision programmes because early evidence
suggested that they were easier for non-surgeons to use and probably safer. It
was only after considerable initial outlay that it became clear that in certain
conditions of use, these newer devices were associated with an increase in rare
adverse events, including tetanus.

Similarly, while injections, vaginal rings and so on
initially seem to be safe, issues such as STI infections, and HIV infection and
resistance after stopping PrEP, may emerge. It is important that
promotion and safety surveillance programmes operate at the same pace,
alongside each other.

9. PrEP spin-offs. One
notable ‘side-effect’ of VMMC is that it has reached men and engaged them in other
care programmes. As well as bringing men, who usually test later than women, into
HIV testing and STI services, VMMC has been a gateway to other health and
social provision for men and has enabled programmes on mental health,
masculinity, gender-based violence and other issues. PrEP will reach a variety
of different populations. As well as being integrated into contraception,
family planning and harm reduction services, it may be a way of introducing
reticent users to them.

10. Strengthening global
advocacy.
Circumcision was an HIV prevention method of proven effectiveness,
but also one that required new thinking and consistent advocacy to realise.
PrEP, like VMMC, challenges conservative thinking and old models. This however
is as much an opportunity as a challenge if it enables coalition-building
between national health ministries, normative bodies such as the World Health Organization, national
and regional surveillance programmes such as the CDC (Centers for Disease Control and Prevention) and ECDC (European Centre for Disease Prevention and Control), and community-based
advocacy organisations such as AVAC. If handled well, PrEP could re-energise
HIV advocacy and activism by creating new engagement with key affected
populations and bolster the fight against HIV at a time when it
is feared that some gains made in the last two decades could be lost.