Regulatory Decision Summary for TRUVADA

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):

emtricitabine, tenofovir disoproxil fumarate

Therapeutic area:


Type of submission:

Supplement to a New Drug Submission

Control number:

What was the purpose of this submission?

The purpose of this Supplemental New Drug Submission was to seek market authorization for Truvada (emtricitabine and tenofovir disoproxil fumarate) as pre-exposure prophylaxis (PrEP) of human immunodeficiency virus type 1 (HIV-1) infection.

Why was the decision issued?


Health Canada considers that the benefit/risk profile of Truvada is favourable for use as prophylaxis in HIV-1 uninfected men who have sex with men (MSM), and in HIV-1 serodiscordant couples.

The primary clinical efficacy and safety data supporting this new indication are derived from two international, Phase III, placebo-controlled efficacy trials, one trial (iPrEx trial) in HIV-1 uninfected men who have sex with men (MSM), and the other (Partners PrEP) in HIV-1 serodiscordant couples.


Both Phase III trials demonstrated the superiority of once-daily oral Truvada over placebo in preventing HIV1 acquisition through sexual exposure when offered as part of a comprehensive prevention strategy that included monthly HIV testing, risk reduction counseling, provision of condoms, and treatment of any sexually-transmitted infections. In these populations and trial settings, Truvada reduced the risk of HIV infection by 42% relative to placebo in the iPrEx trial, and by 75% relative to placebo in the Partners PrEP trial.

The relative efficacy of Truvada was substantially greater among subjects with a high degree of adherence, particularly as evidenced by the testing for quantifiable drug concentrations. In addition, among the MSM population, the relative efficacy of Truvada was greater for those who engaged in unprotected receptive anal intercourse.


The major risks associated with use of Truvada for the PrEP indication include development of drug resistance, and drug toxicity related to kidney, bone, and hepatic flares in persons infected with hepatitis B virus (HBV) - as noted with Truvada use in the treatment of HIV-1 infection.

In the two Phase III trials, uninfected subjects receiving Truvada had comparable safety and tolerability to uninfected subjects who received placebo. No new safety issues were identified. In general, adverse events were balanced between treatment groups. No evidence of hepatic flares was observed among the limited number of subjects with acute or chronic HBV infection enrolled in these trials.

Although a small imbalance was observed in the rates of creatinine elevations between the Truvada and placebo groups across multiple trials, renal toxicity was generally uncommon, was mostly mild, rarely serious, and at all times manageable. Discontinuations of medication for any reason were infrequent and generally balanced between groups.

With respect to bone safety, subjects receiving Truvada in the iPrEx trial had small but statistically significant mean decreases in bone mineral density (BMD) compared to baseline and relative to placebo. Bone mineral density losses greater than 5% from baseline at the spine were observed in 14% of Truvada subjects compared with 6% of placebo subjects. Of note, among subjects with greater than 5% decrease from baseline in BMD at the spine, five subjects (all taking Truvada ) also had evidence of treatment-emergent hypophosphatemia. After discontinuation of Truvada these changes all reversed towards baseline levels. In all clinical trials, bone fractures were balanced between treatment arms and predominantly appeared to be trauma-related.

The detection of resistant viruses in the pivotal trials was limited to isolates from small numbers of subjects who were in the acute stage of HIV-1 infection at baseline and received active drug. The Truvada Product Monograph emphasizes the importance of screening potential candidates for PrEP for acute signs and symptoms of HIV infection and for risk behavior in the month preceding evaluation, and also emphasizes the use HIV diagnostic methods that are sensitive to detect acute or early infection.

Overall Benefit-Risk Assessment

Once-daily oral Truvada, taken as part of a comprehensive risk-reduction program, significantly reduced new HIV-1 acquisitions compared with placebo in populations of high-risk MSMs and in serodiscordant heterosexual couples. The totality of the data supports the conclusion that the benefits of Truvada for PrEP outweigh the risks. The decision to prescribe Truvada for the prevention of sexual acquisition of HIV infection should carefully weigh the individual’s risks for acquiring HIV, their understanding of the importance of adherence to medication, and their potential for development of renal or bone toxicity. Risk mitigation strategies by both the prescriber and user will further diminish potential risks. 


Decision issued

Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.