September 2015: The World Health Organization has released updated Guideline on when to start ART and PrEP for HIV reflecting the realities and research that demonstrate all of the benefits offered by access to antiretroviral (ARV) drugs. The updated guidelines recognise that antiretroviral treatment access upon diagnosis saves lives, averts serious illnesses, and prevents new infections, and that access to the treatment as pre-exposure prophylaxis (PrEP) can protect those at substantial risk of becoming infected. World leaders and policy makers now need to support and respond to the recommendations by adding or aligning the necessary resources for countries to adopt the standard of care required.
The updated guidelines reaffirm (through cumulative research over recent years) that antiretroviral therapy (ART) should be initiated among everyone living with HIV at any CD4 cell count, to prevent death and serious illness on a global scale – whilst many developed nations have already reacted to this evidence within local guidelines and access policy, such as Australia. The goal now will be to assure access and afford ART in all nations. Secondly, the use of daily oral pre-exposure prophylaxis (PrEP) is also recommended as a prevention choice for people at substantial risk of HIV infection as part of combination prevention approaches.
Cost Effectiveness and Affordability
Assessing PrEP cost-affordability by accurately predicting broader-scale use and uptake, beyond trial settings, for the likelihood of averting new infections now needs to weighed-up in each country and region against the cost of expansion of ART to all PLHIV globally. This may entail many trade-offs particularly dependent upon individual uptake, behaviours such as adherence and condom use, background HIV-incidence, and a range of country specific policy and funding arrangements for meeting drug costs, whilst also appraising matters such as incremental cost-effectiveness ratios (ICERs).
Cost-modelling is under conjecture whether PrEP is, or will be, cost-effective everywhere and for whom, and is highly dependent upon regional target population characteristics of risk in line with the population level requiring ART (which is also preventative).
Whilst demonstration projects and open-label trials for PrEP continue, which may include cost-effectiveness components, studies of real-life field implementation will be crucial to answer – especially in limited resource settings – what proportion of resources for treatment and prevention should be spent on PrEP?
It is estimated by the WHO in the updated guidelines that ‘substantial risk’ of HIV infection is defined by an incidence of HIV infection in the absence of PrEP that is sufficiently high (>3% incidence) to make offering PrEP potentially cost-saving (or cost-effective). Offering PrEP to people at substantial risk of HIV infection maximizes the benefits relative to the risks and costs.
Meantime, in resource rich nations such as the UK, two PrEP cost-effectiveness studies have concluded wider rollout of PrEP programmes to gay men at risk of HIV infection would not be cost effective unless the PrEP drug price was cut substantially to be more affordable. Part of their modelling analysis suggested that overall PrEP effectiveness is 64%, not the 86% seen in PROUD (a recently reported study among gay men that the WHO also bases its updated guidelines upon).
Furthermore, studies into other PrEP drug candidates are underway such that most effective form of PrEP still requires further comparison before the best – most effective and cost-effective – drug is known. Nonetheless, we know already that current tenofovir-based treatment is highly effective when taken as recommended, as it has been the most vastly studied – and even if diminished prevention benefit may occur through wider access (outside of trial settings) it is still predicted to be effective, although cost-effectiveness at current pricing needs to be ascertained. However, without regulatory approval no PrEP option can be rolled out where it is most needed.
ART for Everyone, PrEP for Some
Although ART is meant for everyone living with HIV and is an essential part of health and life in that instance; PrEP on the other hand is not meant for everyone, all of the time. If done well, though, initial PrEP introduction activities will enable policy-makers and programme planners to answer the questions of who can benefit most from PrEP, how to provide it safely and efficiently, how to integrate PrEP into combination treatment and prevention programmes, and what kind of health system support is needed to ensure successful implementation.
The extraordinary feat of proving PrEP’s efficacy (in studies) may turn out to have been easier than ensuring that it is used (and utilised) well (in the real world). This is not unique to PrEP and insights can be gleaned from experiences with implementation of other novel strategies. Ensuring that PrEP fulfils its potential as part of high-impact combination HIV prevention strategy requires establishing additional evidence, education, support services and resources, as well as the regulatory framework and cost scenarios for access to PrEP.
The two recommendations are being made available on an early-release basis because of their potential to significantly reduce the number of people acquiring HIV infection and dying from HIV-related causes and significantly impact global public health. In 2016 WHO will follow-up with fully updated Consolidated Guidelines on Treatment and Prevention which will consist of comprehensive clinical recommendations together with revised operational and service delivery guidance to support implementation.
The ambitious UNAIDS Fast-Track targets for 2020, including achieving major reductions in HIV-related mortality and new HIV infections and the 90–90–90 targets*, will require countries to further accelerate their HIV responses in the coming years. Much greater effort is also needed to ensure that key and vulnerable populations and adolescents gain access to essential HIV treatment and prevention services. Implementation of the recommendations in this guideline will contribute to achieving these goals and to ultimately ending the AIDS epidemic as a major public health threat by 2030.
* 90-90-90 refers to 90% of the world UN population tested for HIV (knowing their status), with 90% of those on ART, and 90% of those with undetectable viral load (improving health and providing co-benefit of reduced transmissibility of HIV). This equates to, roughly, 73% of all people living with HIV obtaining undetectable viral load.WHO Updated (Early Release) Guidelines:
Additional Recommended Reading:
http://www.thebody.com/content/76567/stop-shaming-hiv-treatment-fatigue-and-detectabili.html Image Source: World Health Organisation