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Tablets of Truvada, the tenofovir/emtricitabine combination used for HIV pre-exposure prophylaxis

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.[1]

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.[2] PrEP is intended for use with condoms, so that each method can compensate for essential or casual efficacy deficits of the other.[1][3]

Contents

Medical guidelinesEdit

 
The clinical practice guideline for PrEP published by the Centers for Disease Control

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[1]
  • anyone who is not in a monogamous relationship with an HIV negative person, and who...
  • 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[1]

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.[4] Any deleterious effect of Truvada on kidney function usually reverses with drug discontinuation,[5] but irreversible kidney damage can rarely occur.[citation needed]

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[6]
  • Persons with kidney problems, especially decreased renal functions, have increased safety problems with using PrEP[6]
  • Persons with hepatitis B have increased safety problems with using PrEP[6]
  • Women who are pregnant or breastfeeding should speak with their doctors about potential risk to their children[6]
  • 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[6]

ResearchEdit

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.[7] In 2008, the iPrEx study demonstrated 42% reduction of HIV infection among men who have sex with men,[8] and subsequent analysis of the data has suggested that 99% protection is achievable if the drugs are taken every day.[9]

In December 2015, the IPERGAY study was published[10] 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.[6][11]

PrEP approaches with agents besides oral Truvada are currently in clinical trials not listed here.[citation needed]

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[12] 72% by applicator count[13]
iPrEx Oral emtricitabine/tenofovir Men who have sex with men and transgender women 42% reduction of HIV infection.[8] 99% reduction estimated with daily adherence[9] 54% detectable in blood[14]
Partners PrEP Oral emtricitabine/tenofovir; oral tenofovir African heterosexual couples Reduction of infection by 73% with Truvada and 62% with tenofovir[15] 80% with Truvada and 83% with tenofovir[16] detectable in blood
TDF2 Oral emtricitabine/tenofovir Botswana heterosexual couples 63% reduction of infection[4] 84% by pill count[17]
FEM-PrEP Oral emtricitabine/tenofovir African heterosexual females No reduction (study halted due to low adherence) <30% with detectable levels in blood[18]
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][4] <30% with detectable levels in blood[19]
Bangkok Tenofovir Study Randomised, double-blind Oral tenofovir Thai male injection drug users 48.9% reduction of infection[20] 84% by directly observed therapy and study diaries[21]
IPERGAY Randomized, double-blind Oral emtricitabine/tenofovir French gay males 86% reduction of infection[10][22] (video summary) 86% with detectable levels in blood[10]
PROUD Randomized, open-label Oral tenofovir-emtricitabine High-risk men who have sex with men in England 86% reduction of HIV incidence[23]
HPTN 083 Randomized, double-blind Cabotegravir versus emtricitabine/tenofovir ongoing

AdoptionEdit

 
  Approved
  Approved for off-label use
  Ongoing and planned demonstration projects
  Completed demonstration projects
  No planned demonstration project
  No data
In the United Kingdom, Scotland was the only nation to approve the use of PReP

Approval for useEdit

The CDC amended its guidelines for HIV prevention recommending pre-exposure prophylaxis with Truvada to high infection risk populations on 14 May 2014,[24] due to research indicating prophylactic effectivity preventing transmission from mother to child.[15] 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."[25]: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."[26]: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."[11]

As of 2017, numerous countries have now approved the use of PrEP for HIV/AIDS prevention, including the United States, France, Norway,[27] Australia,[28] Israel,[29] Canada,[29] Kenya, South Africa, the European Union[30][31] and Taiwan.[32]

Politics and cultureEdit

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.[33][34][35]

Availability and pricingEdit

PrEP drugs can also be expensive, with a prescription for PrEP drugs costing of the order of £350/month.[36] Some health organizations, including NHS England,[37] have challenged the funding of PrEP.

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.[38]

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.[39]

Generic PrEP medications are already available at significantly lower costs via online pharmacies.[40] 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.[41][40][42]

See alsoEdit

ReferencesEdit

  1. ^ a b c d e f g h Centers for Disease Control and Prevention (30 September 2014). "CDC - Pre-Exposure Prophylaxis (PrEP)". Centers for Disease Control and Prevention. Retrieved 28 December 2014. 
  2. ^ Naswa S, Marfatia YS (2011). "Pre-exposure prophylaxis of HIV". Indian J Sex Transm Dis. 32: 1–8. PMC 3139281 . PMID 21799568. doi:10.4103/0253-7184.81246. 
  3. ^ Gilead Sciences. "Important Safety Information About TRUVADA for PrEP". Gilead Sciences. Retrieved 12 July 2015. 
  4. ^ a b c Celum, CL (December 2011). "HIV preexposure prophylaxis: new data and potential use.". Topics in antiviral medicine. 19 (5): 181–5. PMID 22298887. 
  5. ^ Michael Carter (18 February 2014). "Truvada PrEP does not harm the kidneys, trial shows". Aidsmap. Retrieved 13 January 2017. 
  6. ^ a b c d e f United States Public Health Service. "Preexposure Prophylaxis for the Prevention of HIV Infection in the United States - 2014" (PDF). Centers for Disease Control and Prevention. 
  7. ^ Denton PW, Estes JD, Sun Z, et al. (January 2008). "Antiretroviral pre-exposure prophylaxis prevents vaginal transmission of HIV-1 in humanized BLT mice". PLoS Medicine. 5 (1): e16. PMC 2194746 . PMID 18198941. doi:10.1371/journal.pmed.0050016. 
  8. ^ a b Grant RM, Lama JR, Anderson PL, et al. (December 2010). "Preexposure chemoprophylaxis for HIV prevention in men who have sex with men". New England Journal of Medicine. 363 (27): 2587–99. PMC 3079639 . PMID 21091279. doi:10.1056/NEJMoa1011205. 
  9. ^ a b "PrEP: PK Modeling of Daily TDF/FTC (Truvada) Provides Close to 100% Protection Against HIV Infection". TheBodyPRO.com. Retrieved 28 February 2015. 
  10. ^ a b c Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Préau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Doré V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF (December 4, 2015). "On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection". New England Journal of Medicine. 373: 2237–2246. PMID 26624850. doi:10.1056/NEJMoa1506273. Retrieved December 18, 2015. 
  11. ^ a b "WHO expands recommendation on oral pre-exposure prophylaxis of HIV infection (PrEP)" (PDF). World Health Organization. November 2015. Retrieved 18 December 2015. 
  12. ^ Andrei G, Lisco A, Vanpouille C, et al. (October 2011). "Topical tenofovir, a microbicide effective against HIV, inhibits herpes simplex virus-2 replication". Cell Host & Microbe. 10 (4): 379–389. PMC 3201796 . PMID 22018238. doi:10.1016/j.chom.2011.08.015. 
  13. ^ Mansoor, Leila Essop; Karim, Quarraisha Abdool; Yende-Zuma, Nonhlanhla; MacQueen, Kathleen M.; Baxter, Cheryl; Madlala, Bernadette T.; Grobler, Anneke; Karim, Salim S. Abdool (19 March 2014). "Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial". AIDS and Behavior. 18 (5): 811–819. ISSN 1090-7165. PMC 4017080 . PMID 24643315. doi:10.1007/s10461-014-0751-x. 
  14. ^ "Adherence Indicators and PrEP Drug Levels in the iPrEx Study" (PDF). Retrieved 23 December 2015. 
  15. ^ a b Celum, C; Baeten, JM (February 2012). "Tenofovir-based pre-exposure prophylaxis for HIV prevention: evolving evidence". Current Opinion in Infectious Diseases. 25 (1): 51–57. PMC 3266126 . PMID 22156901. doi:10.1097/QCO.0b013e32834ef5ef. 
  16. ^ Baeten, Jared M.; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R.; Campbell, James D.; Wangisi, Jonathan; Tappero, Jordan W.; Bukusi, Elizabeth A.; Cohen, Craig R. (2 August 2012). "Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women". New England Journal of Medicine. 367 (5): 399–410. ISSN 0028-4793. PMC 3770474 . PMID 22784037. doi:10.1056/NEJMoa1108524. 
  17. ^ "TDF2 STUDY OF PRE-EXPOSURE PROPHYLAXIS (PrEP) AMONG HETEROSEXUAL MEN AND WOMEN IN BOTSWANA: KEY FACTS" (PDF). Centers for Disease Control and Prevention. Retrieved 23 December 2015. 
  18. ^ "Top Stories: Poor Adherence Crippled PrEP Efficacy in Women's Study - by Tim Horn". aidsmeds.com. Retrieved 23 December 2015. 
  19. ^ "Top Stories: Failed VOICE PrEP Trial Failed to Preempt Lies About Adherence". aidsmeds.com. Retrieved 23 December 2015. 
  20. ^ Choopanya K, Martin M, et al. (June 2013). "Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial". The Lancet. 381 (9883): 2083–2090. PMID 23769234. doi:10.1016/S0140-6736(13)61127-7. 
  21. ^ "Bangkok Tenofovir Study: PrEP for HIV prevention among people who inject drugs" (PDF). CDC Fact Sheet. Centers for Disease Control and Prevention. Retrieved 23 December 2015. 
  22. ^ Gilles Pialoux. "Ipergay: La Prep "à la demande", ça marche fort (quand on la prend)". 
  23. ^ Dolling, David I.; Desai, Monica; McOwan, Alan; Gilson, Richard; Clarke, Amanda; Fisher, Martin; Schembri, Gabriel; Sullivan, Ann K.; Mackie, Nicola (2016-01-01). "An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis". Trials. 17: 163. ISSN 1745-6215. PMC 4806447 . PMID 27013513. doi:10.1186/s13063-016-1286-4. 
  24. ^ "Pre-Exposure Prophylaxis (PrEP)". Centers for Disease Control and Prevention. Retrieved 28 February 2015. 
  25. ^ "Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant couples, men and transgender women who have sex with men at high risk of HIV: recommendations for use in the context of demonstration projects." (PDF). WHO. July 2012. 
  26. ^ "Policy brief: Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations, 2014" (PDF). WHO. July 2014. 
  27. ^ "Norway becomes first country to offer free PrEP - Star Observer". starobserver.com.au. Retrieved 12 January 2017. 
  28. ^ "Truvada gets green light for Australian HIV prevention". 6 May 2016. Retrieved 13 January 2017. 
  29. ^ a b "Canada and Israel OK Truvada as PrEP to Prevent HIV". POZ. 1 March 2016. Retrieved 12 January 2017. 
  30. ^ "EU approves HIV prevention drug". News.com.au. 2016-07-22. Retrieved 12 January 2017. 
  31. ^ "European Medicines Agency - News and Events - First medicine for HIV pre-exposure prophylaxis recommended for approval in the EU". ema.europa.eu. Retrieved 12 January 2017. 
  32. ^ "Pre-Exposure Prophylaxis (PrEP) for HIV Prevention" (PDF). Retrieved 12 January 2017. 
  33. ^ McNEIL, DONALD (23 May 2014). "Are We Ready for H.I.V.’s Sexual Revolution?". The New York Times. Retrieved 26 February 2017. 
  34. ^ "Why I am a Truvada Whore". OUT magazine. 20 May 2014. Retrieved 12 January 2017. 
  35. ^ "'Truvada Whore' Stigma Endures Among Doctors and LGBTs". The Advocate. 11 August 2014. Retrieved 12 January 2017. 
  36. ^ "NHS watchdog to weigh cost of HIV prevention drug Prep". BBC News. 7 June 2016. Retrieved 12 January 2017. 
  37. ^ "Make PrEP available". tht.org.uk. Terrence Higgins Trust. Retrieved 12 January 2017. 
  38. ^ "HIV campaigners win NHS drug battle". BBC News Online. 2 August 2016. Retrieved 4 August 2016. 
  39. ^ "Scotland approves HIV-preventing PrEP drugs". PinkNews. 10 April 2017. Retrieved 26 May 2017. 
  40. ^ a b Wilson, Clare (9 January 2017). "Massive drop in London HIV rates may be due to internet drugs". New Scientist. Retrieved 12 January 2017. 
  41. ^ "Dramatic fall in London HIV 'may be due to internet drugs'". Evening Standard. 10 January 2017. Retrieved 12 January 2017. 
  42. ^ "HIV 'may soon be wiped out in London' after dramatic drop in new infections". The Independent. 11 January 2017. Retrieved 12 January 2017. 

Further readingEdit

External linksEdit