Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2018 Oct 1;4(4):215-224.
doi: 10.1016/S2055-6640(20)30312-5.

How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP

Victoria Pilkington  1 , Andrew Hill  2 , Sophie Hughes  3 , Nneka Nwokolo  4 , Anton Pozniak
Affiliations
Editorial

How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP

Victoria Pilkington et al. J Virus Erad. .

Abstract

Background: Tenofovir/emtricitabine (TDF/FTC) used as pre-exposure prophylaxis (PrEP) has proven benefits in preventing HIV infection. Widespread use of TDF/FTC can only be justified if the preventative benefits outweigh potential risks of adverse events. A previous meta-analysis of TDF/FTC compared to alternative tenofovir alafenamide (TAF)/FTC for treatment found no significant difference in safety endpoints when used without ritonavir or cobicistat, but more evidence around the safety of TDF/FTC is needed to address concerns and inform widespread use.

Methods: A systematic review identified 13 randomised trials of PrEP, using either TDF/FTC or TDF, versus placebo or no treatment: VOICE, PROUD, IPERGAY, FEM-PrEP, TDF-2, iPrEX, IAVI Kenya, IAVI Uganda, PrEPare, PARTNERS, US Safety study, Bangkok TDF study, W African TDF study. The number of participants with grade 3/4 adverse events or serious adverse events (SAEs) was compared between treatment and control in the meta-analysis. Further analyses of specific renal and bone markers were also undertaken, with fractures as a marker of bone effects and creatinine elevations as a surrogate marker for renal impairment. Analyses were stratified by study duration (</>1 year of follow up).

Results: The 13 randomised trials included 15,678 participants in relevant treatment and control arms. Three studies assessed TDF use only. The number of participants with grade 3/4 adverse events was 1306/7504 (17.4%) on treatment versus 1259/7502 (16.8%) on control (difference=0%, 95% confidence interval [CI] -1% to +2%). The number of participants with SAEs was 740/7843 (9.4%) on treatment versus 795/7835 (10.1%) on no treatment (difference=0%, 95% CI -1% to +1%). The number of participants with creatinine elevations was 8/7843 on treatment versus 4/7835 on control (difference=0%, 95% CI 0%-0%). The number of participants with bone fractures was 217/5789 on treatment versus 189/5795 on control (difference=0%, 95% CI 0% to 1%). There was no difference in outcome between studies with <1 versus >1 year of randomised treatment.

Conclusions: In this meta-analysis of 13 randomised clinical trials of PrEP in 15,678 participants, there was no significant difference in risk of grade 3/4 clinical adverse events or SAEs between TDF/FTC (or TDF) and control. Furthermore, there was no significant difference in risk of specific renal or bone adverse outcomes. The favourable safety profile of TDF/FTC would support more widespread use PrEP in populations with a lower risk of HIV infection.

Keywords: Pre-exposure prophylaxis (PrEP), Safety, HIV, tenofovir, emtricitabine, kidney, bone density, adverse events.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Flowchart denoting study selection process from identification to inclusion
Figure 2.
Figure 2.
Display of safety data and forest plot of PrEP versus control for serious adverse events
Figure 3.
Figure 3.
Display of safety data and forest plot of PrEP versus control for grade 3/4 adverse events
Figure 4.
Figure 4.
Display of safety data and forest plot of PrEP versus control for grade 3/4 creatinine elevations
Figure 5.
Figure 5.
Display of safety data and forest plot of PrEP versus control for creatinine elevations of all grades (1-4)
Figure 6.
Figure 6.
Display of safety data and forest plot of PrEP versus control for bone fractures
Figure 7.
Figure 7.
Graph summarising the differences in occurrence of all adverse event types, between PrEP and control arms (number of events per total number of people in that safety analysis)
See this image and copyright information in PMC

References

    1. UNAIDS UNAIDS Data 2017. Available from: www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_e... ( accessed May 2018).
    1. Granich R, Crowley S, Vitoria M et al. . Highly active antiretroviral treatment as prevention of HIV transmission: review of scientific evidence and update. Curr Opinion HIV AIDS. - PMC - PubMed
    1. Rodger A, Cambiano V, Bruun T et al. . Risk of HIV transmission through condomless sex in MSM couples with suppressive ART: the PARTNER2 study extended results in gay men. AIDS 2018. July 2018. Amsterdam, Netherlands. Abstract WEAX0104LB.
    1. Bavinton B, Grinsztejn B, Phanuphak N, Jin F. HIV treatment prevents HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil. IAS 2017. July 2017, Paris, France. Abstract 5469.
    1. World Health Organization HIV/AIDS programme guidance on pre-exposure oral 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. Available at http://apps.who.int/iris/bitstream/handle/10665/75188/9789241503884_eng.... ( accessed May 2018). - PubMed

Publication types

LinkOut - more resources