Starting from here – what PrEP programmes can learn from circumcision

Funders, health providers and advocates should take lessons from the rollout of voluntary medical male circumcision (VMMC) as an HIV prevention measure in Africa if they wish to hasten access to programmes providing pre-exposure prophylaxis (PrEP), researchers argue in the International Journal of STD and AIDS.

Their article adds to similar papers on the lessons that PrEP implementers can learn from the history of contraception.

Jason Reed of Jhpiego, Rupa Patel of Washington University in St Louis and Rachel Baggaley of the World Health Organization start by saying that VMMC and PrEP are very different HIV prevention measures. The first is a one-off medical intervention whose effects last for life, but whose efficacy is in the region of 60-70%. The other is a medication that needs to be taken daily or regularly, but which achieves almost 100% efficacy with good adherence. But, they add, there are many lessons from the implementation of VMMC programmes that can also apply to PrEP, particularly in the areas of sustainability, demand creation and community engagement.

As reported recently by aidsmap.com from the International AIDS Conference, PrEP is slowly gaining a foothold in lower-income countries, though still largely as a series of demonstration projects. South Africa and Kenya both have national PrEP strategies they are beginning to implement, with smaller programmes underway in Zimbabwe, eSwatini (Swaziland) and Senegal. In Asia, Thailand and Vietnam have programmes for men who have sex with men and trans women, as well as pilot programmes for sex workers in India.

But we are a long way from the three million people UNAIDS has adopted as its target for PrEP access by 2020. And a number of national programmes are learning the hard way that PrEP can be offered but isn’t always taken, with retention a problem. As the authors of the present paper say, “It is challenging to engage healthy, HIV-uninfected people, many of whom are young, and to encourage them to consider a medical intervention to prevent something that may or may not happen at some future date.”

The original UNAIDS target for VMMC was 20.8 million males circumcised by 2016. Although this ambitious target was not reached, over 15 million men, almost all in Africa, have now been circumcised to reduce their and their communities’ vulnerability to HIV.

What lessons can be learned from the rollout of VMMC that might speed up the introduction of PrEP? The writers make ten points.

Ten points

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.