Pre-exposure prophylaxis

PrEP, an acronym from Pre-Exposure Prophylaxis, is the use of prescription drugs as a strategy for the prevention of HIV/AIDS by people who do not have HIV/AIDS. It 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 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. But people who use PrEP must commit to taking the drug every day and seeing their health care provider for follow-up every 3 months."[1]

One of Truvada's active ingredients, tenofovir disoproxil (TDF), is a nucleotide analog reverse transcriptase inhibitor. TDF effectively blocks 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]

Medical uses

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:

Reasons to avoid

Reasons for not using PrEP include the following:

Adverse effects

The PrEP studies have shown the drugs to be safe, with few side effects. Generally, minor side effects such as nausea or diarrhea resolve themselves within the first few months.[5] Any deleterious effect of Truvada on kidney function usually reverses with drug discontinuation,[6] but irreversible kidney damage can rarely occur.

History

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

The terms "pre-exposure prophylaxis" and "PrEP" most commonly refer to an HIV-prevention strategy where antiretrovirals are used to protect HIV-negative people from HIV infection. In the United States, the HIV antiviral Truvada was approved for PrEP by the Food and Drug Administration on 16 July 2012.[7] The CDC amended its guidelines for HIV prevention recommending pre-exposure prophylaxis with Truvada to high infection risk populations on 14 May 2014,[8] due to research indicating prophylactic effectivity preventing transmission from mother to child.[9] Prior to that date, Truvada was only approved to treat existing HIV infections.

PrEP has been gaining a lot of attention and focus, especially within the battle against AIDS in New York City, a metropolis known for the epidemic's fatality. Andrew Cuomo, Governor of New York has pledged his battle to end AIDS by 2020. According to a New York Times article, Cuomo intends to dramatically drop the infection number to 750 by 2020 from about 3000 in 2013 and 14,000 in 1993. In a city that has a large gay population, Cuomo intends to target his gay male audience. In addition to the use of condoms, Cuomo hopes that PrEP will continue to reduce the number of infections. However, the drug has met some sort of resistance as users may be noted as "Truvada whores," or people who feel enabled to be more promiscuous and less safe in their sex practices due to a perceived heightened sense of security from H.I.V. infection because of the drug. Overall, the fight against HIV infection seems to be going strong. Infection rates have fallen 28% overall from 2007 to 2012.[10]

In July 2014 the World Health Organization issued guidelines saying it "strongly recommends men who have sex with men consider taking antiretroviral medicines as an additional method of preventing HIV infection." [11]

In the United Kingdom, PrEP, which costs around £400 a month, 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 will now (subject to an appeal by the NHS) be considered for funding along with "13 other treatments including treatments for children with cystic fibrosis, for prosthetic limbs and certain types of auditory implants for deafness."[12]

Places that have approved PrEP

Research

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.[18] In 2008, the iPrEx study demonstrated 42% reduction of HIV infection among men who have sex with men,[19] and subsequent analysis of the data has suggested that 99% protection is achievable if the drugs are taken every day.[20]

In December 2015, the IPERGAY study was published[21] looking at an alternative strategy of "on-demand" PrEP where Truvada was taken 2–24 hours before sexual activity and only continued for 2 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 9 month follow-up of the study. As of December 2015, non-continuous PrEP methods have not been endorsed by WHO or national guidelines.[4][22]

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

Study Type of PrEP Study Population Efficacy Percent of patients who took medication (adherence)
CAPRISA 004 Pericoital tenofovir gel South African females 39% reduction of HIV infection[23] 72% by applicator count[24]
iPrEx Oral emtricitabine/tenofovir Men who have sex with men and transgender women 42% reduction of HIV infection.[19] 99% reduction estimated with daily adherence[20] 54% detectable in blood[25]
Partners PrEP Oral emtricitabine/tenofovir; oral tenofovir African heterosexual couples Reduction of infection by 73% with Truvada and 62% with tenofovir[9] 80% with Truvada and 83% with tenofovir[26] detectable in blood
TDF2 Oral emtricitabine/tenofovir Botswana heterosexual couples 63% reduction of infection[5] 84% by pill count[27]
FEM-PrEP Oral emtricitabine/tenofovir African heterosexual females No reduction (study halted due to low adherence) <30% with detectable levels in blood[28]
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][5] <30% with detectable levels in blood[29]
Bangkok Tenofovir Study Oral tenofovir Thai male injection drug users 48.9% reduction of infection[30] 84% by directly observed therapy and study diaries[31]
ANRS - Ipergay Oral emtricitabine/tenofovir French gay males 86% reduction of infection[21][32] (Video summary) 86% with detectable levels in blood[21]

See also

References

  1. 1 2 3 4 5 6 7 8 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. doi:10.4103/0253-7184.81246. PMC 3139281Freely accessible. PMID 21799568.
  3. ↑ Gilead Sciences. "Important Safety Information About TRUVADA for PrEP". Gilead Sciences. Retrieved 12 July 2015.
  4. 1 2 3 4 5 6 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.
  5. 1 2 3 Celum, CL (December 2011). "HIV preexposure prophylaxis: new data and potential use.". Topics in antiviral medicine. 19 (5): 181–5. PMID 22298887.
  6. ↑ http://www.aidsmap.com/iTruvadai-PrEP-does-not-harm-the-kidneys-trial-shows/page/2827796/
  7. ↑ "FDA approves first drug for reducing the risk of sexually acquired HIV infection" (Press release). Food and Drug Administration. Retrieved 28 February 2015.
  8. ↑ "Pre-Exposure Prophylaxis (PrEP)". Centers for Disease Control and Prevention. Retrieved 28 February 2015.
  9. 1 2 Celum, C; Baeten, JM (February 2012). "Tenofovir-based pre-exposure prophylaxis for HIV prevention: evolving evidence". Current Opinion in Infectious Diseases. 25 (1): 51–7. doi:10.1097/QCO.0b013e32834ef5ef. PMC 3266126Freely accessible. PMID 22156901.
  10. ↑ Barro, Josh (3 July 2014). "Pill to Prevent H.I.V. Gets a Prominent Backer: Andrew Cuomo". The New York Times. Retrieved 30 November 2014.
  11. ↑ Hellmann, Melissa (11 July 2014). "WHO says all men who have sex with men should take antiretroviral drugs". Time. Retrieved 20 June 2015.
  12. ↑ "HIV campaigners win NHS drug battle". BBC News Online. 2 August 2016. Retrieved 2016-08-04.
  13. ↑
  14. ↑
  15. 1 2 Canada, Israel OK Truvada PrEP
  16. ↑
  17. ↑
  18. ↑ 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. doi:10.1371/journal.pmed.0050016. PMC 2194746Freely accessible. PMID 18198941.
  19. 1 2 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. doi:10.1056/NEJMoa1011205. PMC 3079639Freely accessible. PMID 21091279.
  20. 1 2 "PrEP: PK Modeling of Daily TDF/FTC (Truvada) Provides Close to 100% Protection Against HIV Infection". TheBodyPRO.com. Retrieved 28 February 2015.
  21. 1 2 3 "On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection". New England Journal of Medicine. 373: 2237–2246. December 4, 2015. doi:10.1056/NEJMoa1506273. Retrieved December 18, 2015.
  22. ↑ "WHO expands recommendation on oral pre-exposure prophylaxis of HIV infection (PrEP)" (PDF). World Health Organization. November 2015. Retrieved December 18, 2015.
  23. ↑ 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): 379–89. doi:10.1016/j.chom.2011.08.015. PMC 3201796Freely accessible. PMID 22018238.
  24. ↑ Mansoor, Leila Essop; Karim, Quarraisha Abdool; Yende-Zuma, Nonhlanhla; MacQueen, Kathleen M.; Baxter, Cheryl; Madlala, Bernadette T.; Grobler, Anneke; Karim, Salim S. Abdool (2014-03-19). "Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial". AIDS and Behavior. 18 (5): 811–819. doi:10.1007/s10461-014-0751-x. ISSN 1090-7165. PMC 4017080Freely accessible. PMID 24643315.
  25. ↑ "Adherence Indicators and PrEP Drug Levels in the iPrEx Study" (PDF). Retrieved December 23, 2015.
  26. ↑ Baeten, Jared M.; Donnell, Deborah; Ndase, Patrick; Mugo, Nelly R.; Campbell, James D.; Wangisi, Jonathan; Tappero, Jordan W.; Bukusi, Elizabeth A.; Cohen, Craig R. (2012-08-02). "Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women". New England Journal of Medicine. 367 (5): 399–410. doi:10.1056/NEJMoa1108524. ISSN 0028-4793. PMC 3770474Freely accessible. PMID 22784037.
  27. ↑ "TDF2 STUDY OF PRE-EXPOSURE PROPHYLAXIS (PrEP) AMONG HETEROSEXUAL MEN AND WOMEN IN BOTSWANA: KEY FACTS" (PDF). Centers for Disease Control and Prevention. Retrieved December 23, 2015.
  28. ↑ "Top Stories : Poor Adherence Crippled PrEP Efficacy in Women's Study - by Tim Horn". www.aidsmeds.com. Retrieved 2015-12-23.
  29. ↑ "Top Stories : Failed VOICE PrEP Trial Failed to Preempt Lies About Adherence". www.aidsmeds.com. Retrieved 2015-12-23.
  30. ↑ 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. doi:10.1016/S0140-6736(13)61127-7. PMID 23769234.
  31. ↑ "Bangkok Tenofovir Study: PrEP for HIV prevention among people who inject drugs" (PDF). CDC Fact Sheet. Centers for Disease Control and Prevention. Retrieved December 23, 2015.
  32. ↑ Gilles Pialoux. "Ipergay : La Prep "à la demande", ça marche fort (quand on la prend)".

External links

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