A large international study among gay men and transgender women,the so-called iPrEx trial, suggested that pre-exposure prophylaxys (PrEP) by a tenofovir/emtricitabine combination can reduce the risk of HIV infection by at least 92% when the pills are taken consistently. Other trials subsequently confirmed PrEP effectiveness. 

PrEP is not intended as a stand-alone intervention, but rather as part of a multi-faceted strategy involving the use of condoms as well as regular follow-ups including for HIV and other sexually transmitted diseases testing

By Marieke Bak

The Promise of PrEP for HIV Prevention

Despite significant progress in the past decades, the global HIV/AIDS epidemic remains a major public health issue. In 2015, an estimated 36.7 million people worldwide were living with HIV, representing a global prevalence of 0.8%. Declines in new HIV infections have slowed in recent years, and in some regions the incidence of HIV continues to grow. One of the most rapidly accelerating epidemics is currently taking place in Eastern Europe and Central Asia, where new HIV infections rose by 57% between 2010 and 2015. Thus, the fight against HIV continues, and has become intensified since the United Nations committed to ending the epidemic by the year 2030.

Recognising that universal access to testing and treatment alone will not stop the epidemic, UNAIDS has been calling for a “much stronger primary prevention response” and recommends that 25% of national HIV budgets is spent on prevention. Moreover, countries are urged to use a combination approach to HIV prevention, consisting of behavioural, biomedical and structural interventions.

However, current biomedical and behavioural interventions are of limited effectiveness in many settings. Behavioural strategies such as celibacy and mutual monogamy are not reliable or realistic for many people worldwide. In addition, negotiating condom use can be difficult or impossible in some settings, or the effect of condoms on sexual pleasure may lead to non-use. Moreover, it was found that self-reported consistent condom use only reduces the risk of HIV acquisition by 63% to 72% among men who have sex with men (MSM), one of the key populations at risk for HIV infection, and by 80% among heterosexual men and women. Treatment as prevention (TasP) also has limitations, since it is dependent upon partners’ medication adherence to ensure suppressed viral load. Moreover, viral suppression rates are not high enough to prevent new infections solely through TasP.

Considering these limitations, there has been a need for additional prevention strategies that are effective and do not place the risk of HIV infection in other people’s hands. Provision of pre-exposure prophylaxis (PrEP) may be such a strategy. PrEP is a daily pill consisting of a combination of tenofovir/emtricitabine, two anti-retroviral drugs. It is branded by Gilead Sciences as Truvada which was approved for prevention in 2012 by the Food and Drug Administration (FDA) in the United States. In contrast to PEP, or post-exposure prophylaxis, PrEP is taken before exposure to HIV to prevent any possible transmission. It works by blocking an enzyme called HIV reverse transcriptase, thereby preventing HIV from establishing itself in the body.

A large international study among gay men and transgender women, the so-called iPrEx trial, suggested that PrEP can reduce the risk of HIV infection by at least 92% when the pills are taken consistently. Other trials subsequently confirmed PrEP effectiveness. However, because it is not 100% effective and because it does not protect from other sexually transmitted diseases (STDs), PrEP is not intended as a stand-alone intervention, but rather as part of a multi-faceted strategy involving the use of condoms as well as regular follow-ups. These visits should take place every three months and consist of HIV testing, testing for other STDs, assessment of side effects, and counselling on medication adherence and risk reduction.

In addition to the promising effectiveness data, one of the main advantages of PrEP is that it puts HIV prevention directly under the control of the at-risk individual. Because PrEP separates the act of prevention from the sexual encounter, it can be used without sexual partners knowing. This makes PrEP a “gender-sensitive” strategy: it does not require consent from a male partner, which is a major advantage in settings where women are disempowered to discuss condom use.

With PrEP, the individuals become empowered to take control of their own health, and it has been suggested that PreP might “transform HIV infection just like hormonal contraception transformed family planning”. Also, it enables those who are in serodiscordant relationships to have sex without condom, and is a welcome new option for couples who wish to conceive. Lastly, a well-functioning PrEP programme with regular follow-ups might have the added benefit of strengthening healthcare systems and HIV services.

There are some side effects associated with Truvada for PrEP, although these are generally minor symptoms such as nausea and headaches that resolve within a few weeks. In rare cases, people may experience small changes in kidney function or a decrease in bone mineral density. An updated version of Truvada known as Descovy, that is thought to have fewer side effects, is currently being investigated in the so-called “Discover study”.

Because PrEP does not prevent transmission of other sexually transmitted diseases, there have been fears that PrEP might be used as a “party drug” and lead to increasing rates of other STDs. In fact, in the iPrEx study as well as in a meta-analysis by the World Health Organisation (WHO), it was shown that PrEP does not lead to an increase in the number of STDs and has no effect on condom use. On the contrary, a recent study found that PrEP use can actually reduce the incidence of STDs among men who have sex with men, because it involves routine screening and treatment of other STDs.

The World Health Organization now recommends that PrEP should be offered as a choice to key populations affected by HIV as well as to anyone else at substantial risk of HIV infection. However, Truvada is currently approved for use as PrEP only in a handful of countries, while a number of countries are conducting pilots, and access is expanding slowly across the world. Global availability remains limited at 2% of the target set by UNAIDS to get three million people on PrEP by 2020.

At the moment, Truvada for PrEP has been approved in the United States, Canada, Australia, Peru, South Africa, Kenya, Zimbabwe, Israel, and the European Union. Approval is pending in Brazil and Thailand. In the European Union, PrEP has been approved by the European Medicines Agency (EMA) although the implementation of PrEP programmes is the responsibility of each member state separately. To date, only France and Norway have made PrEP available as part of their healthcare system. Scotland recently announced that it will do the same.

The hesitation to fund PrEP often stems not only from seemingly unfounded worries for risk compensation, but also from the high cost of PrEP. Even in low- and middle income countries where generic versions of Truvada are generally available, drug prices still present a barrier to the accessibility of PrEP and may lead to developing countries having to make trade-offs between prevention and treatment. Indeed, PrEP is more expensive than other HIV prevention methods, but it can be a cost-effective tool in some settings, especially when delivered to key population. According to the WHO, offering PrEP can be cost-effective when the HIV incidence is greater than 3 per 100 persons. A study published in the Lancet reported that by preventing the costs of lifetime HIV treatment, PrEP may eventually lead to healthcare savings, especially when the drug patents expire and the cost drops.

Since it is widely recognised that treatment alone is not sufficient to eradicate HIV, and given the high effectiveness of PrEP, countries should make an effort to provide access to PrEP among those at risk of HIV infection. While keeping in mind that PrEP is part of a combination prevention approach, scaling up of PrEP programmes will be a significant step towards ending the global HIV/AIDS epidemic.