Pre-exposure prophylaxis (PrEP) is the preemptive use of drugs to prevent disease in people who have not yet been exposed to the disease-causing agent. In particular, the term is used to refer to the use of antiviral drugs that attack the lifecycle of the HIV virus as a strategy for the prevention of HIV/AIDS. PrEP is an optional treatment which may be taken by people who are HIV negative, but who have substantial, higher-than-average risk of contracting an HIV infection.
Currently, the only drug which any health organization recommends for HIV/AIDS PrEP is Truvada, which is the brand name of the Gilead Sciences drug combination of tenofovir/emtricitabine. The Centers for Disease Control says that "PrEP is a powerful HIV prevention tool and can be combined with condoms and other prevention methods to provide even greater protection than when used alone". However, people who use PrEP must commit to taking the drug every day and seeing their health care provider for follow-up every three months.
Truvada's active ingredients, tenofovir disoproxil (TDF) and emtricitabine (FTC), are nucleotide analog reverse transcriptase inhibitors. TDF and FTC effectively block HIV from incorporating its genetic material into the host's genome, and thus prevents HIV infection. PrEP is intended for use with condoms, so that each method can compensate for essential or casual efficacy deficits of the other.
In the United States, federal guidelines recommend the use of PrEP for HIV negative people with the following characteristics:
- in a serodiscordant sexual relationship, meaning that the HIV-negative person regularly has sex with an HIV positive person
- anyone who is not in a monogamous relationship with an HIV negative person, and who...
- is a man who has sex with men, and...
- does not regularly use condoms during sex, and who has sex with people of unknown HIV status who are at high risk of contracting HIV
- anyone who has injected illicit drugs in the past six months, shared recreational drug injection equipment with other drug users in the past six months, or who has been in treatment for injection drug use in the past six months
The PrEP studies have shown the drugs to be generally safe, with few side effects. Generally, minor side effects such as nausea or diarrhea resolve themselves within the first few months. Any deleterious effect of Truvada on kidney function usually reverses with drug discontinuation, but irreversible kidney damage can rarely occur.
Reasons for not using PrEP include the following:
- Persons with HIV should never use PrEP, and an HIV test is necessary before starting to use PrEP
- Persons with kidney problems, especially decreased renal functions, have increased safety problems with using PrEP
- Persons with hepatitis B have increased safety problems with using PrEP
- Women who are pregnant or breastfeeding should speak with their doctors about potential risk to their children
- Minors may not have access to services which complement the effective use of PrEP, and need extra attention from their doctor if they use PrEP
Most PrEP studies utilize the drug tenofovir or a tenofovir/emtricitabine combination (Truvada) that is delivered orally. Initial studies of PrEP strategies in non-human primates showed a reduced risk of infection among animals that receive ARVs prior to exposure to a simian form of HIV. A 2007 study at UT-Southwestern (Dallas) and the University of Minnesota showed PrEP to be effective in "humanized" laboratory mice. In 2008, the iPrEx study demonstrated 42% reduction of HIV infection among men who have sex with men, and subsequent analysis of the data has suggested that 99% protection is achievable if the drugs are taken every day.
In December 2015, the IPERGAY study was published looking at an alternative strategy of "on-demand" PrEP where Truvada was taken 2–24 hours before sexual activity and only continued for two days afterwards. In a population of 400 gay men in France and Canada at high risk for HIV, this strategy led to an 86% drop in HIV infections over the average ninth month follow-up of the study. As of December 2015, non-continuous PrEP methods have not been endorsed by WHO or national guidelines.
|Study||Type||Type of PrEP||Study Population||Efficacy||Percent of patients who took medication (adherence)|
|CAPRISA 004||Double-blind, randomized||Pericoital tenofovir gel||South African females||39% reduction of HIV infection||72% by applicator count|
|iPrEx||Oral emtricitabine/tenofovir||Men who have sex with men and transgender women||42% reduction of HIV infection. 99% reduction estimated with daily adherence||54% detectable in blood|
|Partners PrEP||Oral emtricitabine/tenofovir; oral tenofovir||African heterosexual couples||Reduction of infection by 73% with Truvada and 62% with tenofovir||80% with Truvada and 83% with tenofovir detectable in blood|
|TDF2||Oral emtricitabine/tenofovir||Botswana heterosexual couples||63% reduction of infection||84% by pill count|
|FEM-PrEP||Oral emtricitabine/tenofovir||African heterosexual females||No reduction (study halted due to low adherence)||<30% with detectable levels in blood|
|VOICE 003||Oral emtricitabine/tenofovir; oral tenofovir; vaginal tenofovir gel||African heterosexual females||No reduction in oral tenofovir or vaginal gel arms [oral emtricitabine/tenofovir arm ongoing]||<30% with detectable levels in blood|
|Bangkok Tenofovir Study||Randomised, double-blind||Oral tenofovir||Thai male injection drug users||48.9% reduction of infection||84% by directly observed therapy and study diaries|
|IPERGAY||Randomized, double-blind||Oral emtricitabine/tenofovir||French gay males||86% reduction of infection (video summary)||86% with detectable levels in blood|
|PROUD||Randomized, open-label||Oral tenofovir-emtricitabine||High-risk men who have sex with men in England||86% reduction of HIV incidence|
|HPTN 083||Randomized, double-blind||Cabotegravir versus emtricitabine/tenofovir||ongoing|
Approval for use
The CDC amended its guidelines for HIV prevention recommending pre-exposure prophylaxis with Truvada to high infection risk populations on 14 May 2014, due to research indicating prophylactic effectivity preventing transmission from mother to child. Prior to that date, Truvada was only approved to treat existing HIV infections.
In 2012, the World Health Organization issued guidelines for PreP which said that PreP "may be considered as a possible additional intervention" for the uninfected partner in couples where one partner is HIV-positive, when "additional HIV prevention choices for them are needed" and made similar recommendations for men and transgender women who have sex with men. It noted that "international scientific consensus is emerging that antiretroviral drugs, including PrEP, significantly reduce the risk of sexual acquisition and transmission of HIV regardless of population or setting.":8,10,11 In 2014, on the basis of further evidence, the WHO updated the recommendation for men who have sex with men to state that PreP "is recommended as an additional HIV prevention choice within a comprehensive HIV prevention package.":4 In November 2015 the WHO expanded this further, on the basis of further evidence, and stated that it had "broadened the recommendation to include all population groups at substantial risk of HIV infection" and emphasized that PreP should be "an additional prevention choice in a comprehensive package of services."
As of 2017[update], numerous countries have now approved the use of PrEP for HIV/AIDS prevention, including the United States, France, Norway, Australia, Israel, Canada, Kenya, South Africa, the European Union and Taiwan.
Politics and culture
Moves toward the widespread adoption of PrEP has been divisive, both politically, and within gay culture, with some seeing PrEP as being likely to be misused, and to undermine existing safer sex policies. The pejorative term "Truvada Whore" has been used by some in the gay community who perceive PrEP users as irresponsible.
Availability and pricing
In 2016, the funding of PrEP in the English NHS was the subject of a judicial review, National AIDS Trust v NHS Service Commissioning Board, after NHS England argued that as it was a preventive drug, the Health and Social Care Act 2012 made its provision be the responsibility of local councils. The High Court of Justice found that local authorities did not have sole responsibility for HIV prevention in England. PrEP would now (subject to an appeal by the NHS) be considered for funding.
Scotland, which has a devolved healthcare system, became the first part of the United Kingdom to approve the use of PrEP in the NHS in April 2016.
Generic PrEP medications are already available at significantly lower costs via online pharmacies. The unprecedented reduction in the HIV infection rate in London in 2016 has variously been ascribed to the introduction of new early intervention approaches to HIV treatment, and to the availability of generic PrEP online.
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