Pre-exposure prophylaxis (PrEP) uses antiretroviral drugs (ARVs) to protect HIV-negative people from HIV before potential exposure to the virus.
Trials have shown that when taken consistently and correctly, PrEP is very effective.1 2 3 Truvada is currently the only drug approved for use as PrEP. Truvada is a single pill that is a combination of two ARVs, tenofovir and emtricitabine.
Recognising that PrEP potentially has population-wide benefits, in 2015 the World Health Organization (WHO) released new guidelines and a policy brief recommending that PrEP should be offered as a choice to people who are at substantial risk of HIV infection.4
Previously, PrEP was only recommended for certain key affected populations such as sex workers, men who have sex with men (sometimes referred to as MSM) and people who inject drugs (sometimes referred to as PWID).5 However, it was recognised that this excluded people who are at substantial risk but do not belong to one of these groups.
If not taken routinely and consistently, PrEP is much less effective. Therefore, it is important that any programme offering PrEP provides the service as part of a combination package of prevention initiatives, and does not replace other, more effective methods like condoms.
The case for PrEP
PrEP has been shown to reduce the risk of HIV infection from unprotected sex by over 90%, and from injecting drugs by more than 70%.6 A number of high profile trials have shown how PrEP can be an effective HIV prevention option in a number of different settings.
Started in 2007, the iPrEx study was the first to offer PrEP. PrEP was provided to 2,500 men who have sex with men at 11 sites in six countries on four continents. It found that the HIV infection rate in HIV-negative gay men who were given PrEP was reduced by 44% compared with men taking a placebo. Among those who took PrEP seven days a week, the risk of infection was reduced by 99%.7 Similarly, the IPERGAY study, which offered PrEP at six hospitals in France and Canada, reported an 86% reduction in the HIV infection rate compared to those taking a placebo.8
The Partners PrEP trial recruited 4,758 heterosexual couples in which one partner was living with HIV across Kenya and Uganda. The risk of HIV infection was reduced by 62% among those who took tenofovir and 73% among those who received Truvada.9 Additionally, a number of trials have shown the effectiveness of PrEP in preventing HIV infection among women at a high risk of HIV.10
Moreover, there is no evidence that PrEP leads to a reduction in condom use and other safer sex behaviour. For example, the PROUD Study conducted in the United Kingdom (UK) reported no difference in condom usage or levels of sexually transmitted infections between the group given PrEP and the group that didn’t take the drug.11
It is cost effective
PrEP is estimated to be cost-effective where HIV incidence is greater than 3 per 100 person-years and possibly in places with lower HIV prevalence levels. This level of HIV prevalence remains common among young women in some settings in Southern Africa, some sex workers in Africa and men who have sex with men in many countries.12
PrEP drug costs are lower than HIV treatment costs, both per-dose and for the duration of use. Moreover, PrEP is used as needed as opposed to lifelong for treatment.13 With an estimated cost of less than 5% of an HIV programme’s total budget, PrEP is considered by UNAIDS to be a key component of a Fast-Tracked response.14
There is a demand
Demand for PrEP is rising among people at substantial risk of infection. A multi-country survey of people at higher risk of HIV infection found that 61% of respondents would “definitely” use PrEP if it was available.15 Up to 92% of men who have sex with men surveyed in India said that they were likely to use PrEP.16
In the UK, around half of men who have sex with men have shown an interest in taking PrEP.17 One study has predicted that providing PrEP with annual HIV testing alongside improved treatment services to just a quarter of men who have sex with men in the UK with a high risk of HIV infection, could prevent over 7,000 new HIV infections by 2020.18
PrEP pilot programmes
There are also a growing number of countries with pilot programmes that are demonstrating the potential impact of PrEP as an effective HIV prevention tool. Just a few are outlined below.
The San Francisco experience
San Francisco in the United States of America (USA) was one of the first places to implement PrEP, rolling out the service in 2012.19 Between a quarter and one third of at risk men who have sex with men in San Francisco are now thought to be on PrEP.
In November 2014, roughly 600 men who have sex with men enrolled on PrEP at the Magnet sexual health clinic in the Castro neighbourhood of San Francisco. After one year, there were no new HIV infections among the group. Adherence remained high over time – 95% after one month, and 94% in the seventh month reported that they had missed fewer than three doses during the past week.20
Steve Gibson, Director of the Magnet clinic, said:
"The bottom line is that there were no new HIV infections. We've found that the combination of clinical services combined with benefits navigation is what helps insure that people can start taking the medication the same day, often costing the client nothing." 21
In order to increase PrEP coverage, a website has been launched that sends SMS reminders to new clients to help them adhere to their medication and links them to health professionals and peers via an online social network if they have any questions. They are also supported to select health insurance plans that cover at least a portion of their PrEP costs.22
The PrEP Brazil Study
The PrEP Brazil Study focuses on men who have sex with men and transgender women. It uses a number of innovative ways to increase PrEP adherence, including SMS reminders and engagement through social media.23
Preliminary results of the study are promising with uptake of PrEP over 50%, and notable increases in awareness of the service and knowledge of high-risk sexual behaviour among participants.24
Growing awareness and demand for PrEP is expected to increase its rollout. In 2011, only 22% of men who have sex with men in Brazil had heard about PrEP.25 By 2015, PrEP awareness among this group was 60% in Sao Paulo and Rio de Janeiro, and nearly 95% said that they would like to use PrEP to prevent HIV.26
The SAPPH-IRe project, Zimbabwe
In 2009, the Sister with a Voice programme was launched to strengthen Zimbabwe’s HIV response among sex workers. Within this programme, the SAPPH-Ire project is trialling offering antiretroviral treatment (ART) to women who test positive for HIV and PrEP to women who test negative for HIV.27
Offered at 14 locations, community-based adherence support is provided to both groups where each woman in the programme selects a 'sister', another woman in the programme with whom she attends monthly peer group sessions.28
Their HIV status is kept confidential unless they choose to disclose it, and the programme sisters support each other with medication adherence. SMS reminders are used to encourage women to attend both clinic and medication refill appointments.29
Another key component of the programme is legal advice provided to participants by peer educators. The peer educators inform sex workers of their basic rights and how they can legally protect themselves against violations of those rights.30
"The argument is over about PrEP. If you take the drug, it works, not only in a clinical trial but in the field." - Anthony Fauci, Director, US National Institute of Allergy and Infectious Diseases (NIAID) 31
Scale up of PrEP in Kenya
Kenya and South Africa are the first African countries to begin implementing a PrEP strategy, and to date, have employed small-scale pilot projects to start introducing PrEP. The Bridge to Scale project has now been established in Kenya to scale-up PrEP for HIV prevention.
Awarded US$ 22.3 million in funding in September 2016, the project aims to reach 20,000 people who are at high risk of HIV, including adolescent girls and young women. The project will examine barriers to accessing PrEP and other HIV prevention services for those at highest risk of HIV and aims to find the most effective strategies for implementing PrEP so that it reaches these groups.32
Challenges of PrEP
Availability of PrEP is currently extremely limited, with less than 1% of people at substantial risk of HIV infection having access to it.33
PrEP is slowly being approved by countries. The USA approved PrEP in 2012, and since then Canada, France, South Africa, Kenya and Israel have also rolled out the service. The European Commission approved the use of Truvada for PrEP in August 2016.34 Other countries are also working towards including PrEP in their national HIV programmes.35
To increase access to PrEP in California USA, a company called Nurx is allowing people to get a prescription for PrEP via a mobile app without having to see a doctor. The information put into this app is reviewed by a doctor remotely who decides whether the treatment is suitable for the person. Before they can receive their prescription, they must also have blood and urine tests.36
Attempts to address this include two pilot programmes called Pluspills and UChoose in Cape Town, South Africa. Pluspills is looking into the acceptability and use of PrEP among girls and boys between 15 and 19 years of age, while UChoose is examining PrEP delivery through different contraceptive options among girls aged 16 to 17 years.38
Where knowledge of PrEP is high, demand is also high. However, many people who could benefit from PrEP are still unaware of the service.
One study surveying awareness and acceptability of PrEP among men who have sex with men in Scotland, Wales, Northern Ireland and the Republic of Ireland, found that only one third (34.5%) were aware of PrEP. Men who tested for HIV every six months were most likely to be aware of PrEP.40
Likewise, research from the USA among young men who have sex with men aged 18 to 24, found that only 27% of the sample had heard about PrEP. They were more likely to have heard about PrEP if they were older, better educated, had no permanent residence, had health insurance, or reported having at least one sexually transmitted infection (STI) in their lifetime.41
PrEP needs to be offered as part of a package of HIV prevention services
PrEP is not 100% effective, and therefore it needs to be delivered as part of a comprehensive package of HIV prevention services. These include condoms and lubricant, safer sex counselling, frequent STI check-ups and treatment, and regular HIV testing.42
A range of models for delivering PrEP have been proposed, including STI clinics, primary care clinics, and community-based organisations with links to clinics.43 44 45 However, each of these options presents challenges.
For example, while STI clinics serve a population at risk of HIV infection, most operate on a drop-in or urgent care basis and do not provide ongoing care and monitoring. Conversely, primary care clinics are experienced with ongoing care, but need to be able to identify people eligible for PrEP and offer risk reduction and adherence counselling.46
If not taken routinely and consistently, PrEP is much less effective. People with high levels of adherence have high levels of protection, while lower adherence leads to low or no protection.
One study of three cities in the USA reported very different levels of PrEP adherence among men who have sex with men. In San Francisco, 52% of participants took PrEP daily compared to 35% in Washington DC and just 13.5% in Miami.47
A further 27% of those from Miami, 18% from Washington and 4% from San Francisco only took two doses a week - offering about 70% protection (compared to over 90% if taken daily). Moreover, 11%, 2% and 4% respectively took just one dose a week, offering very little protection; and 4.5%, 2% and 0% of participants had no detectable tenofovir in their blood.48
A number of factors were attributed to this difference in adherence levels including knowledge and awareness of PrEP, its availability and the participants' lifestyle.49
Another factor which can affect adherence is exposure to abuse and violence within a relationship. A study carried out among HIV-serodiscordant couples accross Africa found that women who had experienced verbal, physical, or economic abuse from a partner were more likely to have low PrEP adherence. The reasons given included stress and forgetting, leaving home without pills, and partners throwing pills away.50
To address PrEP adherence issues, two trials, ECLAIR and HPTN 077, are currently investigating the use of long-acting injectable (LAI) antiretrovirals to prevent reliance on daily pill-taking.51
Stigma and discrimination
As with other HIV services, stigma and discrimination can negatively impact upon uptake and adherence to PrEP.
In some settings, PrEP is associated with high-risk sexual activity. It also has the stigma of being related to HIV (which may also relate to other stigmas, such as homosexuality, sex work, and/or drug use) and the stigma of PrEP being an alternative to condoms (as condom use is often associated with responsible sexual activity).52
PrEP-related stigma has been reported by trial participants at a range of sites among different key affected populations spanning several countries. Authorities may also persecute sex workers for the possession of PrEP pills as evidence of sex work53.
Case study: Sex workers and PrEP
Of 440 respondents consulted by the Global Network of Sex Work Projects in 40 countries, only a few staff or volunteers had heard of PrEP. They also held suspicions and scepticism about the treatment, including concerns that it might reduce condom use, be forced on sex workers or facilitate mandatory HIV testing.
The research showed that non-governmental organisations and sex work groups are concerned about a range of issues surrounding PrEP, including cost and discrimination.54
Photo by Jason/ CC BY-NC-ND 2.0
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