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Preparing for Pre-Exposure Prophylaxis

By James Wilton

Spring 2011

Preparing for Pre-Exposure Prophylaxis

Table of Contents


Introduction

What if a person at risk of HIV infection could start taking preventative medications on a regular basis before being exposed to HIV to reduce their risk of infection?

This strategy, known as pre-exposure prophylaxis (or PrEP), is beginning to show promise in research studies and could potentially provide another much needed prevention option for those at risk of infection. Despite its promise, this strategy raises a number of concerns and -- if we aren't prepared -- its introduction could end up doing more harm than good.


PrEP to Prevent HIV Infection

PrEP refers to the use of a medication before an exposure in order to prevent a disease or a condition. For example, medications are commonly used to prevent malaria, tuberculosis and pregnancy.

PrEP to prevent HIV infection would use the same anti-HIV medications as those used to treat people who are HIV-positive. To reduce the risk of infection of HIV-negative individuals, anti-HIV medications would need to be taken on a regular basis both before and after a potential exposure.

This strategy should not be confused with post-exposure prophylaxis (or PEP), which is the use of antiretrovirals after a potential exposure for a limited period of time (28 days).

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The Different Flavours of PrEP

PrEP is one of the most promising biomedical HIV prevention tools in development and is beginning to garner the attention of the media. Headlines such as "A pill a day to keep HIV away" or "Will a pill a day keep HIV at bay?" are catchy but they don't tell the whole story. Taking an anti-HIV pill daily is one possible way PrEP could be used, but it's not the only strategy in development.

In addition to a pill taken orally, the anti-HIV medications used for PrEP could be available in a variety of forms, such as a gel applied topically to the vagina or rectum, a ring inserted into the vagina, or an injection. Researchers are also looking into different dosing schedules, including the use of anti-HIV drugs daily, intermittently (once or twice a week) or coitally (before and after sex).


The Changing Terminology: Microbicides as a Form of PrEP

To those who know what a microbicide is, a gel applied to the vagina or rectum may sound very familiar. A microbicide is an experimental strategy that would involve applying a product -- such as a gel, film or suppository -- into the vagina or rectum to block HIV infection. Although the idea is simple enough, it has been difficult for researchers to figure out what needs to be put in a microbicide for it to work.

Early microbicides contained a variety of chemicals that all failed to reduce the risk of HIV transmission. After several studies produced disappointing results, researchers were forced to re-consider what they were putting into their microbicides and now the majority of newer microbicides in development contain anti-HIV medications.

Microbicides and PrEP are often referred to as distinct prevention strategies but newer microbicides that contain anti-HIV drugs fall under the definition of PrEP -- the use of medications before a potential exposure to prevent a disease. Recognizing medication-based microbicides as a form of PrEP is important because the use of anti-HIV drugs in HIV-negative individuals, whether in pill or gel form, raises cross-cutting concerns, which are the main focus of this article and are discussed later.1


What Is Being Researched?

Although many PrEP strategies are being researched, only a few are in the latter stages of development, including:

These strategies are being researched in a variety of populations, including men who have sex with men, injection drug users, heterosexual serodiscordant couples and heterosexual women. These studies are nearing completion and the results are expected by 2013.

Unfortunately, we won't know in the near future if all types of PrEP will work. Some important PrEP strategies are at the earlier stages of development or lack funding. Therefore, information on their effectiveness may not be available for many years. These strategies include:

(AVAC: Global Advocacy for HIV Prevention tracks the latest information on PrEP research studies currently underway.)


What Evidence Is Available So Far -- Does PrEP Work?

In 2010, two studies released exciting results showing that two different PrEP strategies -- (1) a gel applied vaginally before and after sex and (2) a pill taken daily -- were able to reduce the risk of HIV infection when used by certain populations.

While the results of these studies are promising and show that anti-HIV medications used consistently before and after an exposure can reduce the risk of HIV infection, we still need additional studies to confirm these results before regulatory approval is possible. Research studies currently underway that are investigating PrEP in other populations will tell us more about the effectiveness of these PrEP strategies when used to protect against other routes of HIV transmission.


Partial Protection -- A Cause for Concern

From a quick look at the available evidence, we can see that it's unlikely that PrEP will be highly protective against HIV infection. The PrEP strategies investigated in both the iPrEx and CAPRISA studies provided only moderate protection against HIV and infections still occurred among people using PrEP (even in those who consistently adhered to their medication schedule -- taking a pill every day or applying a gel before and after sex).

Partially protective prevention tools raise several issues. One major concern is the possibility that people using PrEP will engage in more risk behaviours because they falsely believe that they are highly protected against HIV infection. It will be important to develop accurate messaging about the level of protection PrEP provides so people using PrEP can make informed decisions related to their risk-taking behaviours. Partial protection is a potentially challenging concept to communicate and understand. The level of protection provided by PrEP will also influence important decisions made by regulatory authorities and public health agencies related to PrEP access, such as if and when PrEP will become available, who will get it, and how much it will cost.

Our lack of previous experience with partially protective tools may mean that we are unprepared to address these challenges and decisions. Moderately protective tools are uncommon in disease prevention and many of the technologies available to prevent diseases other than HIV, such as childhood vaccines, are highly effective and often provide close to 100% protection. Strategies that are currently available to prevent HIV infection, particularly those that help someone avoid exposure in the first place -- such as condoms, clean needles, HIV testing and reducing the number of sexual partners -- are also highly protective if used consistently.

Because of this partial effectiveness, PrEP will only be beneficial if it does not replace condom use. However, PrEP could reduce HIV infections if it is made available to individuals who are not otherwise willing or able to use condoms. We all know that there are lots of reasons why people don't use condoms either through choice or lack of choice.

The Need for Careful Implementation

If studies confirm that a PrEP strategy is safe and effective in different populations, and it is approved by Canada's regulatory authorities, only half the battle will have been won. Taking a partially effective PrEP and translating it into a reduction in new HIV infections -- a public health benefit -- will be the other, more challenging half of the battle.

The introduction of PrEP to communities outside of a research study raises several concerns. Although a partially protective PrEP has the potential to reduce the number of new infections in Canada, if these concerns are not addressed when PrEP is made available, then PrEP could potentially do more harm than good.4

The remainder of this article outlines the concerns that PrEP raises, the clinical and non-clinical services that will need to be packaged together during the implementation of PrEP, and the role your agency may play in the delivery of PrEP to people at risk of HIV infection.

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Clinic-Based Delivery

PrEP is not going to be a prevention tool that can be handed out freely, like condoms, or picked up at your local community-based organization. Instead, PrEP will need to be delivered in a clinical setting. Clinic-based delivery of PrEP is necessary for a couple reasons. First of all, the anti-HIV drugs used for PrEP will need to be prescribed by a doctor and won't be available "over-the-counter" to the general public. Secondly, we know that HIV-positive individuals who use anti-HIV drugs to treat HIV need to be monitored regularly; the use of these medications in HIV-negative individuals to prevent HIV raises additional safety concerns. PrEP use will need to be closely monitored by a team of healthcare professionals. However, there could still be important roles for community-based organizations to play in raising awareness among the best candidates for PrEP, providing education and supports for individuals who wish to access PrEP, and facilitating clinical follow-ups such as HIV testing.

The safe implementation of PrEP will need to include the following clinic-based services:


HIV Counselling and Testing

PrEP use will need to be restricted to people who are HIV-negative. If PrEP is used by a person who is HIV-positive, their HIV could become drug-resistant. Before a person at risk of infection can start PrEP, an initial HIV test will need to be done to make sure a person is HIV-negative. After starting PrEP, regular HIV counselling and testing will also be needed to check for recent HIV infection. If a test result is positive, PrEP use will need to be discontinued.

Ongoing access to HIV counselling and testing services at community-based clinics or hospitals will play an important role in preventing the development and spread of drug-resistant strains of HIV.


Testing for Drug Resistance

In people who become infected with HIV while using PrEP, the quick discontinuation of medications may reduce, but not completely eliminate, the risk of developing drug resistance. If the virus mutates, the drugs used for PrEP may not work for treatment. This is a major concern because the two drugs being used for PrEP, tenofovir and emtricitabine, are commonly used for the treatment of HIV in Canada (the drugs can be found in Emtriva, Viread, Truvada and Atripla).

Access to drug resistance testing will be important to determine whether or not the HIV has become drug-resistant. This information will help inform which anti-HIV drugs are selected for treatment should an individual become infected with HIV while on PrEP.


Medical Monitoring

Although tenofovir and emtricitabine are two of the least toxic drugs available for the treatment of HIV, they are not without their safety concerns. These drugs, when used in combination with other anti-HIV medications to treat HIV, are associated with decreases in kidney function, loss of bone density, and hepatitis flares in people infected with hepatitis B.

Access to regular medical monitoring to assess if the medications are causing harm to the body will be important to make sure people using PrEP remain healthy. Monitoring may include bone density scans, kidney and liver tests, and screening for hepatitis B.


Management of Side Effects

Tenofovir and emtricitabine commonly cause mild side effects including diarrhea, nausea, headache and fatigue. Side effects may make it difficult for a PrEP user to adhere to their dosing schedule and can negatively affect a person's quality of life.

Regular assessments by healthcare professionals will allow for the side effects to be managed quickly and effectively.


Management of Sexually Transmitted Infections

Sexually transmitted infections can increase a person's risk of becoming infected with HIV and may compromise the level of protection provided by PrEP. The prompt diagnosis and treatment of sexually transmitted infections will be an important prevention tool to be used in combination with PrEP.

Regular assessments by healthcare professionals will allow for the early diagnosis and treatment of sexually transmitted infections.


More About the Evidence on PrEP Safety

The information on the safety of different PrEP strategies is limited but promising. Toxicity, side effects and drug resistance have not been identified as major concerns in the research studies completed to date.

In the CAPRISA 004 study, no significant safety concerns were observed in women using a tenofovir gel before and after sex.2 However, there was a slightly higher frequency of mild diarrhea in the women who used the tenofovir gel. No drug resistance was detected in women who became infected while using the gel.

In two studies of oral PrEP, the daily use of a tenofovir pill was found to be safe and well tolerated by both men who have sex with men (MSM)5 and heterosexual women.6 No side effects, toxicity or drug resistance were detected; however, there was a slightly higher frequency of back pain among MSM taking the tenofovir pill.

In the iPREX study, a daily pill containing tenofovir in combination with emtricitabine was studied in MSM.3 The pill was generally safe and well tolerated but a few safety concerns were identified. Compared to men who were given a placebo, the men who took the tenofovir pill were more likely to experience nausea during the first four weeks of taking the anti-HIV pill and some men also experienced a decrease in kidney function. No drug resistance was detected in participants who became infected while taking PrEP but drug resistance was detected in two men who started taking the anti-HIV pill when they were already infected with HIV. One case of drug resistance was definitely the result of PrEP but the other man may have been infected with a drug-resistant strain.

The lack of safety concerns observed in research studies is positive but does not mean safety will not be an issue. The use of anti-HIV drugs over a longer period of time may raise additional safety concerns. Research studies do not provide information on the safety of PrEP in populations that are excluded from studies, such as adolescents, pregnant women and people with underlying health conditions. Also, many participants in research studies have difficulty adhering to PrEP and this may explain the low level of side effects and toxicity.


The "Medicalization" of HIV/AIDS Prevention

There is a concern that the introduction of biomedical prevention strategies, such as PrEP, will lead to the "medicalization" of prevention -- that is, shift the focus of HIV/AIDS prevention to medical solutions and away from effective behavioural, structural and community-based interventions.

The view that HIV is a medical problem -- best addressed by "quick-fix" biomedical tools and managed by healthcare professionals -- could undermine current prevention efforts and needs to be avoided.7 Behavioural interventions that reduce risk behaviours and structural interventions that address social inequalities that place people at risk of infection are integral to current HIV prevention efforts and should continue to play an important role in HIV prevention.

Furthermore, the distinction between behavioural and biomedical approaches is a false one. To be effective, biomedical tools require behaviour changes; and for PrEP to have a public health impact, behavioural interventions will be needed to promote people's awareness and use of PrEP, support adherence, and prevent increases in risk behaviours.


Opportunities for AIDS Service Organizations

Community-based AIDS service organizations (ASOs) in Canada have long been at the forefront of HIV/AIDS prevention and have years of experience advocating, building relationships with communities, addressing social inequalities and promoting behaviour change. If PrEP and other biomedical prevention technologies are introduced, ASOs will play a key role in preventing the "medicalization of prevention" and continuing to fight the HIV epidemic through behavioural, structural and biomedical approaches.

ASOs will also need to be prepared to expand their role to meet the challenges that new biomedical prevention technologies bring and to provide some of the behavioural interventions that need to be delivered along with PrEP during its implementation. Specifically, there may be opportunities for your agency to provide the following non-clinical services:


Outreach and Educational Campaigns

It may seem obvious, but if people at risk of HIV don't use PrEP -- either because they aren't aware of it or because they don't want to use it -- then it's not going to have a large public health impact.

ASOs will play a role in promoting people's awareness and informed use of PrEP, through outreach and public education campaigns. Community members who will most benefit from PrEP will need to be identified, provided with accurate information about the risks and benefits, and connected to clinics where PrEP is available. People at risk of infection who want to use PrEP, but are consistently using more effective methods such as condoms or clean needles, will need to be discouraged from switching to PrEP because it is less protective.

Educational campaigns will also need to warn community members against obtaining anti-HIV medications from sources other than a doctor and using them without medical supervision and guidance. Worryingly, there are already reports of people at risk of infection getting PrEP from HIV-positive friends, people at parties, and the Internet.

As discussed earlier, the use of anti-HIV medications raises several safety concerns and its use without regular clinical monitoring or HIV testing may be dangerous. Also, if a person at risk of infection obtains PrEP from a non-medical source, there is no guarantee that they are using PrEP in the correct way to reduce their risk of infection. For example, they may obtain anti-HIV drugs that are not effective or they may follow the wrong dosing schedule.


Adherence Support

Consistent adherence to a PrEP dosing schedule will be important to get the best level of protection against HIV infection that PrEP can provide. If a person using PrEP misses a dose or does not adhere to the prescribed dosing schedule, then their risk for infection may increase. Adherence may be difficult for many individuals using PrEP, particularly for those who experience side effects or have addiction or mental health issues.

ASOs could provide ongoing adherence support to people using PrEP through adherence counselling, social support programs, and technological and non-technological gadgets that can act as reminders.


Risk-Reduction Counselling

People using PrEP will need to continue to practice safer sex and, if they inject drugs, safer injection practices. PrEP is only expected to be partially protective and with each additional exposure to HIV there is a chance that PrEP will fail and HIV infection will occur. If a person using PrEP feels a false sense of protection against HIV infection and increases their risk behaviours (and number of potential exposures to HIV) -- such as having sex with more partners, using fewer condoms or sharing more needles -- then their risk of HIV infection (and other STIs) will increase.

To support the continued use of other prevention strategies and prevent increases in risk behaviours, prevention workers in ASOs may be able to provide regular risk-reduction counselling to people using PrEP. Counselling should communicate that PrEP is only partially protective and not a replacement for more effective HIV prevention strategies and emphasize the continued need to avoid potential exposures to HIV while using PrEP.


Advocacy

The implementation of PrEP will not be cheap. Anti-HIV drugs are expensive and there will be additional costs for the ongoing clinical and non-clinical services that need to be packaged along with the medications. The high cost is concerning given that many people at high risk of infection may not be able to afford the medications and HIV/AIDS prevention is currently underfunded.

There may be a need for ASOs to bring attention to the social and economic barriers that prevent those at high risk of infection from accessing PrEP. Advocacy may be needed for PrEP medications to be covered by provincial and territorial health insurance plans and to ensure that funding for the implementation of PrEP does not draw resources away from programs that focus on behavioural and structural interventions.

Answering the Call for Comprehensive HIV/AIDS Prevention

The implementation of PrEP will not be simple. Maximizing PrEP's public health benefit will require a comprehensive approach that involves the coordinated efforts of service providers in clinical and non-clinical settings. If we are unprepared to address the issues that PrEP raises, an important opportunity to reduce new infections in Canada may be lost and a host of new problems created.

For years, there have been calls from experts in HIV prevention demanding that our prevention efforts adopt a more comprehensive approach that combines different behavioural, structural and biomedical interventions.8 With the possible introduction of partially protective biomedical technologies, such as PrEP, we are entering a new era in HIV/AIDS prevention in which the need for a comprehensive approach is even more immediate and pressing.


Resources

Strategies for Using Pre-Exposure Prophylaxis (PrEP) to Lower HIV Incidence in Select Populations -- Policy Considerations and Suggestions of the National PrEP Committee: Project Inform, AIDS Vaccine Advocacy Coalition, Community HIV/AIDS Mobilization Project, National Alliance of State & Territorial AIDS Directors. December 1, 2010.

Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex With Men -- Centers for Disease Control and Prevention (CDC)

James Wilton is the project coordinator of the Biomedical Science of HIV Prevention Project at the Canadian AIDS Treatment Information Exchange (CATIE). James has an undergraduate degree in microbiology and immunology from the University of British Columbia.


References

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  2. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168-1174.
  3. Grant RM, Lama JR, Anderson PL et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. New England Journal of Medicine. 2010 Nov 23;(Epub ahead of print).
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  5. Grohskopf L, Gvetadze R, Pathak S et al. Preliminary analysis of biomedical data from the phase II clinical safety trial of tenofovir disoproxil fumarate (TDF) for HIV-1 pre-exposure prophylaxis (PrEP) among US men who have sex with men (MSM). XVIII International AIDS Conference. 2010 Jul 18;Abstract FRLBC102.
  6. Peterson L, Taylor D, Roddy R, Belai G, Phillips P, Nanda K, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. Public Library of Science Clinical Trials. 2007;2(5):e27.
  7. Nguyen V, Bajos N, Dubois-Arber F et al. Remedicalizing an epidemic: from HIV treatment as prevention to HIV treatment is prevention. AIDS. 2010 Dec 9;(Epub ahead of print).
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