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HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans

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Abstract

Purpose

Despite established HIV prevention strategies and broadly available diagnostic strategies in developed western countries, rates of HIV new infections remain high. Alternative strategies for HIV prevention, particularly among men who have sex with men (MSM), are crucial. HIV pre-exposure prophylaxis (PrEP) has been discussed as one additional option that this review seeks to explore.

Methods

An online search identifying PrEP-relevant literature from 1st January 2010 to 1st August, 2015 was performed.

Results

The iPrEx study, first published in 2010, demonstrated a reduction in relative risk (RRR) of HIV seroconversion of 44 % for continuous PrEP with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in MSM. The efficacy of PrEP has been confirmed for continuous PrEP in the PROUD study and for intermittent PrEP in the IPERGAY study (RRR = 86 % in both studies). The PrEP was well tolerated in all studies, and the evolution of HIV resistance has been low. Compensatory increased sexual risk behavior was not observed in recent studies. In contrast to the high efficacy of risk reduction for HIV transmission in MSM, the results of TDF PrEP and TDF/FTC PrEP studies using microbicidal agents or pills among heterosexual women were different (RRR 6–75 %).

Conclusions

Continuous and intermittent PrEP demonstrated high efficacy in preventing HIV seroconversion, notably among MSM. PrEP was well tolerated. Adherence was critical for high efficacy in all studies. Further studies to evaluate implementation strategies and cost-effectiveness in different risk populations are needed as well as drug approval in Europe.

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Abbreviations

AIDS:

Acquired immunodeficiency syndrome

AIDS:

International AIDS conference

CROI:

Conference on retroviruses and opportunistic infections

FDA:

Federal Drug Administration (United States of America)

HIV:

Human immunodeficiency virus

IAS:

International AIDS society conference

INSTI:

HIV integrase inhibitor

IVDA:

Intravenous drug abuse(r)

NNRTI:

Non-nucleosidic reverse transcriptase inhibitor

NRTI:

Nucleoside reverse transcriptase inhibitor

PrEP:

HIV pre-exposure prophylaxis

RRR:

Relative risk reduction

TAF:

Tenofovir alafenamide

TDF/FTC:

Tenofovir disoproxil fumarate/emtricitabine

TDF:

Tenofovir disoproxil fumarate

TFV:

Tenofovir

YMSM:

Young men having sex with men

References

  1. May M, Gompels M, Sabin C. Life expectancy of HIV-1-positive individuals approaches normal conditional on response to antiretroviral therapy: UK Collaborative HIV Cohort Study. J Int AIDS Soc. 2012;15(Suppl 4):18078.

    PubMed Central  Google Scholar 

  2. Cohen MS, McCauley M, Gamble TR. HIV treatment as prevention and HPTN 052. Curr Opin HIV AIDS. 2012;7:99–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hull MW, Montaner JSG. HIV treatment as prevention: the key to an AIDS-free generation. J Food Drug Anal. 2013;21:S95–101.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Beyrer C. Strategies to manage the HIV epidemic in gay, bisexual, and other men who have sex with men. Curr Opin Infect Dis. 2014;27:1–8.

    Article  PubMed  Google Scholar 

  5. van Griensven F, Lind van Wijngaarden JW, Baral S, Grulich A. The global epidemic of HIV infection among men who have sex with men. Curr Opin HIV AIDS. 2009;4:300–7.

    Article  PubMed  Google Scholar 

  6. WHO: Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations [Internet]. [cited 2015 Mar 26]. Available from: http://www.who.int/hiv/pub/guidelines/keypopulations/en/.

  7. Kelesidis T, Landovitz RJ. Preexposure prophylaxis for HIV prevention. Curr HIV/AIDS Rep. 2011.

  8. García-Lerma JG, Cong M-E, Mitchell J, Youngpairoj AS, Zheng Q, Masciotra S, et al. Intermittent prophylaxis with oral truvada protects macaques from rectal SHIV infection. Sci Transl Med. 2010;2:14ra4.

    PubMed  Google Scholar 

  9. García-Lerma JG, Otten RA, Qari SH, Jackson E, Cong M-E, Masciotra S, et al. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. PLoS Med. 2008;5:e28.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Patterson KB, Prince HA, Kraft E, Jenkins AJ, Shaheen NJ, Rooney JF, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011;3:112re4.

    PubMed  PubMed Central  Google Scholar 

  11. Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Van Damme L, Corneli A, Ahmed K, Agot K, Lombaard J, Kapiga S, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012;367:411–22.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372:509–18.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Molina JM, Capitant C, Charreau I, et al. On demand PrEP with oral TDF/FTC in MSM: results of the ANRS Ipergay trial. Program and abstracts of the 2015 Conference on Retroviruses and Opportunistic Infections; Feb 23–26, 2015; Seattle, Washington. Abstract 23LB.

  16. McCormack S, Dunn D. Pragmatic open-label randomised trial of preexposure prophylaxis: the PROUD study. Program and abstracts of the 2015 Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015; Seattle, Washington. Abstract 22LB.

  17. Choopanya K, Martin M, Suntharasamai P, Sangkum U, Mock PA, Leethochawalit M, et al. 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. Lancet. 2013;381:2083–90.

    Article  PubMed  Google Scholar 

  18. Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4:151ra125.

    PubMed  PubMed Central  Google Scholar 

  19. Centers for Disease Control and Prevention (CDC). Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb. Mortal. Wkly. Rep. 2012. pp. 586–589.

  20. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423–34.

    Article  CAS  PubMed  Google Scholar 

  21. Liu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS ONE. 2011;6:e23688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pattacini L, Murnane PM, Baeten JM, Fluharty TR, Thomas KK, Bukusi E, et al. Antiretroviral pre-exposure prophylaxis does not enhance immune responses to HIV in exposed but uninfected persons. J Infect Dis. 2015;211:1943–52.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine II, University Hospital Klinikum rechts der Isar der TUM, Ismaningerstr. 22, 81675, Munich, Germany

    Christoph D. Spinner

  2. Department of Internal Medicine I, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Christoph Boesecke & Jürgen Kurt Rockstroh

  3. Department of Dermatology and Allergology, University Hospital Klinikum rechts der Isar der TUM, Biedersteiner Str. 29, 80802, Munich, Germany

    Alexander Zink

  4. Medical Group Practice, Motzstr. 19, 10777, Berlin, Germany

    Heiko Jessen

  5. ICH Study Center, Grindelallee 25, 20146, Hamburg, Germany

    Hans-Jürgen Stellbrink

  6. Department of Dermatology, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Stefan Esser

  7. German Center for Infection Research (DZIF), Brunswick, Germany

    Christoph D. Spinner, Christoph Boesecke, Alexander Zink & Jürgen Kurt Rockstroh

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  1. Christoph D. Spinner
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Correspondence to Christoph D. Spinner or Stefan Esser.

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Conflict of interest

Dr. Christoph D. Spinner received grants for travel and participation in advisory boards of AbbVie, Bristol-Meyers Squibb, Gilead, Janssen-Cilag, MSD, and ViiV. Grants for investigator initiated studies (ISR) from Gilead Sciences, Janssen-Cilag, and ViiV Healthcare were also given. Dr. Christoph Boesecke received Grants for travel and speakers honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen-Cilag, MSD and ViiV Healthcare as well as research Grants from German Center for Infectious Diseases (DZIF), German Liver Foundation, and NEAT ID. Dr. Alexander Zink received travel Grants from AbbVie, Bristol-Meyers Squibb, Gilead Sciences and MSD. Dr. Heiko Jessen received speaker’s honoraria and participated in advisory boards of ViiV Healthcare, AbbVie Deutschland, Bristol-Myers Squibb, and Gilead Sciences. Grants for investigator initiated studies (ISR) from Gilead Sciences, MSD, and ViiV Healthcare were also given. Prof. Dr. Hans-Jürgen Stellbrink received speaker’s honoraria from AbbVie, Gilead Sciences, MSD, Bristol-Myers Squibb, ViiV Healthcare, and Janssen-Cilag. Prof. Dr. Jürgen Rockstroh received speaker’s honoraria and participated in advisory boards of Abbvie, Bionor, Bristol-Meyers Squibb, Gilead Sciences, Janssen-Cilag, MSD, and ViiV. Grants for investigator initiated studies (ISR) from MSD Sharp and Dohme and Gilead were also given. Dr. Stefan Esser received travel grants and participated in advisory boards of AbbVie, Bionor, Bristol-Meyers Squibb, Gilead Sciences, Janssen-Cilag, MSD, and ViiV. Grants for investigator initiated studies (ISR) from AbbVie, Bristol-Meyers Squibb, Gilead Sciences, Janssen-Cilag, MSD Sharp and Dohme, and ViiV Healthcare were also given.

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Spinner, C.D., Boesecke, C., Zink, A. et al. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans. Infection 44, 151–158 (2016). https://doi.org/10.1007/s15010-015-0850-2

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  • DOI: https://doi.org/10.1007/s15010-015-0850-2

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