1. WHO PrEP Guidance

2. Outline
Public health perspective: HIV prevention matters (and PrEP is a new tool with untapped promise)
WHO HIV strategy and WHO guidance on PrEP
Messaging of PrEP
Future of PrEP (research and scale-up)
Prevention revolution, we do prevention in public health all time:
Aspirin, cholesterol lowering medications
Calcium and vitamin D to prevent fractures
Contraception, some women take a pill every day to prevent pregnancy, if they are not planning to have a baby
You don’t want to get HIV if it comes in your way.
Does it work? Yes, body of clinical trial research that began many years ago.
Nothing in medicine is 100 percent, so it’s pretty darn good.
What about side effects? We have a lot of experience and data, we know it’s safety profile, and that is why we are not proposing to put PrEP in the water like we do with fluoride. It’s a clinical service.

3. From a public health perspective, what is the issue?
PrEP: why would you give a pill to someone who’s negative? Is a pill a simple solution?

4. HIV Testing, Treatment & Viral Suppression
There has been an enormous improvement in the numbers of people who know their HIV status. Currently 79% of people with HIV are estimated to know they are infected. Of them 62% are on ART, and 53% are virally suppressed.

5. Global HIV transmission PERSISTS: Treatment scale-up has ‘masked stagnation in the estimated annual number of new HIV infections’ (Baggaley et al, JIAS)
1. We know that the treat-all approach is where we should be going: ART access will prevent mortality, morbidity and HIV transmission
2. Continuing expansion of treatment is critical for all countries
3. But, treatment scale-up has ‘masked stagnation in the estimated annual number of new HIV infections’

6. New HIV infections Global, 2018

7. What happens when you don’t have services for certain populations: E.g. MSM HIV epidemic in the Philippines
When you don’t offer appropriate services to certain key populations, for e.g. this is what happens.
Increase in HIV transmission in certain regions of the world, and in certain populations.
Ross et al, IJID, 2015:

8. So to summarize, thus far:
Globally, we are not seeing a decrease in new HIV infections in adults
We are doing a good job in scaling up treatment
HIV prevention + treatment go together
More to do at global, regional, national and local levels: fast-track approach
Interventions to prevent HIV that are evidence-based should be offered to those that can benefit as part of fast- tracking to 2020 (and 2030)
We are not there yet.

9. We have the tools to prevent HIV (except a vaccine)

10. HIV testing technology has improved (e.g. rapid tests, self-testing )
WHO HIV testing guidelines (2015):

11. Condoms + lubricants
WHO-UNAIDS-UNFPA statement on condoms:

12. VMCC (circumcision prevents HIV)

13. Needle and syringe programmes
What is the comprehensive harm reduction package for people who inject drugs?
Needle and syringe programmes
Opioid substitution therapy (OST) and other evidence-based drug dependence treatment
HIV testing and counselling
Antiretroviral therapy
Prevention and treatment of STIs
Condom programmes for people who inject drugs and their sexual partners
Targeted information, education and communication for people who inject drugs and their sexual partners
Prevention, vaccination, diagnosis and treatment for viral hepatitis
Prevention, diagnosis and treatment of TB.
27/10/2019
Guidelines on HIV prevention and treatment for Key Populations (WHO, 2016):
Globally, around 13 million people inject drugs and 1.7 million of them are living with HIV. Injecting drug use accounts for approximately 10% of HIV infections globally and 30% of those outside of Africa. Regional HIV prevalence rates are high in people who inject drugs in all parts of the world (up to 15.5% in East and Southern Africa). People who use drugs are also disproportionately affected by hepatitis C. The estimated global prevalence of hepatitis C in people who inject drugs is 67%. Further, worldwide there are approximately 2.2 million HIV–hepatitis C virus co-infections of which more than half are in people who inject drugs.
Guidelines on HIV prevention and treatment for Key Populations (WHO, 2016):

14. Recent years, oral PrEP (containing TDF) has become available in some countries
TDF/FTC

15. What does the WHO actually say about PrEP?

16. WHO recommendation for PrEP (2015)
Oral PrEP (containing TDF) should be offered as an additional prevention choice for people at substantial risk of HIV infection as part of combination prevention approaches.
strong recommendation
high quality evidence
WHO released a broad recommendation for PrEP in 2015 for all people at substantial risk.

17. Features of the Recommendation
Enabling
Not population specific
For people at substantial HIV risk (provisionally defined as HIV incidence > 3 per 100 person–years in the absence of PrEP)
An additional prevention choice within combination prevention
Condoms and lube
Harm reduction
HIV testing and links to ART
Provide PrEP with comprehensive support
Adherence counselling
Legal and social support
Mental health and emotional support
Contraception and reproductive health services
Not just a pill
HIV testing is a first step and links to ART are key for those seeking PrEP who are diagnosed as HIV-positive.
WHO has evolved in its guidance on PrEP with this specific recommendation, in that it is not prescriptive only to groups like men who have sex with men or serodiscordant couples. It is meant to be ‘enabling’ and really to support countries to start implementing PrEP for those individuals at highest risk for HIV.
Substantial risk is defined as an HIV incidence of more than 3 per 100 person/years, and that itself could be defined by a population (for example, MSM in an urban setting) or a particular district or setting (whether that is a particular area in a country with incidence above that threshold, or an actual facility where incidence is above 3%).
It is really important for us to also underscore that PrEP being offered to individuals should be part of a combination prevention package, which requires also comprehensive support.

18. Systematic review results: HIV Infection outcome
Favours PrEP
Favours Placebo
The recommendation itself is based on a systematic review and meta-analysis that was conducted, where the whole body of evidence looking at TDF-containing regimens was considered. We looked at 10 placebo-controlled randomized clinical trials, and 3 observational studies in total. The RCTs are listed here on the left hand side of the slide.
A number of outcomes were considered, but the primary outcome was HIV infection, and the key finding when the data was pooled was that PrEP was significantly effective in reducing risk of HIV infection across gender, PrEP regimen, dosing and mode of acquisition.
And what is critical when looking at individual clinical trials (and observational studies) is the impact of adherence on PrEP’s effectiveness. The higher the adherence, the higher the effectiveness.
Data available from 10 placebo-controlled RCTs and 3 observational studies. Primary results not downgraded for inconsistency because heterogeneity was explained by adherence level
Note: Results from overall analysis had significant heterogeneity; therefore, results stratified by adherence level for GRADE tables
PrEP significantly effective in reducing risk of HIV infection across gender, PrEP regimen, dosing, and mode of acquisition.
↑ adherence, ↑ effectiveness

19. Adherence and Effectiveness
And again to illustrate the role of adherence on reducing HIV acquisition across these PrEP studies, this plot shows that as you move to higher levels of adherence on the x-axis, from left to right, you also have a greater reduction in HIV risk. It’s also important to note that in the two well publicized trials in women, VOICE and FEM-PrEP, that did not show PrEP working in this population, the underlying reason was that the participants did not adhere to their PrEP.
So main message is, PrEP works, when taken.

20. Safety of PrEP drugs in pregnancy and breastfeeding
Pharmacology studies
ART
HBV treatment
PrEP trials
Systematic reviews/meta-analyses
We also looked at the data on safety of TDF containing PrEP drugs in pregnancy and breastfeeding. That was systematically looked at by including pharmacology studies, ART, HBV treatment studies (since tenofovir is a WHO recommended drug for treatment of hepB according to our 2015 guidelines), limited data from PrEP trials, and also systematic reviews and meta analyses that have been conducted.
Given available safety data, there does not appear to be a safety-related rationale for prohibiting PrEP during pregnancy and lactation or for discontinuing PrEP in HIV-negative women receiving PrEP who become pregnant (and are at continued risk of HIV acquisition)
(Mofenson, AIDS, 2016)

21. Paper can be accessed here: https://www. ncbi. nlm. nih

22. Recurrent concerns expressed by ministries of health
Cost
Where, Who
Safety
Drug resistance
Behavioral disinhibition
Pregnancy and hormonal contraception
Adherence
>18 years
Why should we prioritize PrEP when treatment is our immediate priority?
Where do we start? Which populations ? Where to offer services?
'Toxic drugs' for people without HIV
People taking PrEP, esp. with poor adherence: Will this result in lots of drug resistance use?
Offering PrEP will mean people stop using condoms, have more sexual partners, more STIs
PrEP isn't safe during pregnancy and should be stopped when women become pregnant
What about drug interactions?
Lots of the trials had poor results with poor adherence
Many concerns esp. for adolescent girls
Given the global debate on PrEP, and its role in HIV prevention, the same concerns are raised from one country to the next.
First, cost is a big issue, particularly as health budgets are limited and treatment gaps persist, and this is particularly a concern in many European countries.
How to actually offer PrEP and the type of service delivery model that is appropriate for one’s setting was a big concern as well. And all these other issues are flagged by providers, potential PrEP users, public health officials, including the emergence of HIV drug resistance, behavior disinhibition, and risk compensation.
Questions over safety of PrEP in pregnant and lactating women are being raised. And then there are issues over whether people will actually adhere to taking a pill every day.

23. WHO PrEP Implementation Tool 2017
Module
1. Clinical– how to provide PrEP safely & effectively – screening, monitoring, adherence
2. Counsellors – how to support to people considering, starting, continuing on PrEP
3. Pharmacists – how to provide PrEP drugs
4. Testing providers – laboratory services, screening, monitoring
5. Leaders – essentials for understanding benefits and limitations
6. Regulatory officials – how to overcome regulatory issues
7. Strategic planning – prioritization for maximum benefit and impact
8. Site planning – organizing PrEP services at the site level
9. Monitoring & Evaluation – how to monitor PrEP programmes
10. Community educators and advocates – involving communities
11. PrEP users – information for and by people who are taking or considering using PrEP
12. Adolescents & Young Adults - for programs aiming to reach youth aged 15-24
Evidence Annex – a synthesis of available evidence to support the guidance
WHO released a PrEP implementation tool in 2017 in modular format with each module with information in each focused on a particular stakeholder group – for example, clinicians, pharmacists, PrEP users, and adolescents and young adults.

24. New Dosing Regimen for MSM, 2019
86% reduction in HIV risk in the placebo controlled randomised phase
97% reduction in open label extension including in infrequent users (9.5 pills/mo)
WHO released a new technical update on event-driven PrEP in 2019 – a shorter regimen of 4 pills for men who have sex with men. This dosing regimen has been found to be highly efficacious at preventing HIV in men who have sex with men.
“Loading dose”
Is appropriate if sex can be predicted or delayed by at least 2 hours, or occurs less than 2 times per week.

25. Positive messaging + marketing
Add slide from San Francisco if you can (Bob’s slide)

26. 27/10/201927/10/2019

29. South Africa

31. How does PrEP implementation look now?

32. Countries With PrEP Policies, July 2019
There has been huge increase in the number of countries that have PrEP policies since 2015, when only the United States was implementing PrEP.
37 countries have pending policies
30+ Countries have policies pending

33. Prevention is often perceived as complicated, difficult, and boring
Prevention is often perceived as complicated, difficult, and boring. But it doesn’t have to be, especially in the era of PrEP.
Prevention is contextual and often perceived as “complicated, difficult, and boring”
Interest, prioritisation and funding for HIV prevention interventions and programmes from countries, donors and communities have been inadequate over the last decade. For example, in 2015 only 7% of the estimated funds required to reach enough people who inject drugs with evidence-based prevention services to have an impact on the epidemic was available from international donors [20].