How Effective Is PrEP in Preventing HIV?

Reports of Infection in Canadian Man in Raises Questions, Concerns

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It was widely reported on February 25, 2016 that a man taking the HIV prevention drug, Truvada, contracted the virus despite being fully adherent to once-daily drug regimen. The news raised serious concerns among some as to how effective the strategy—known as HIV pre-exposure prophylaxis (or PrEP)—actually is ensuring that HIV-negative persons remain uninfected.

In their report, investigators with the Maple Leaf Medical Clinic (MLMC) in Canada confirmed that a 43-year-old gay man had tested positive for HIV while on PrEP, and that a review of both pharmacy records and the patient’s therapeutic drug tests (used to measure drug concentration in blood) paid evidence to the individual's high level of compliance.

Further genetic testing eventually revealed that the man had acquired a "rare" mutated strain of HIV, which was resistant to the two individual drug agents that comprise Truvada.

So the question remains: is this case as "rare" as some in the media have reported? Or does the incident, in fact, expose a possible chink in the armor of this much-touted HIV prevention strategy?

What Is the Real-World Efficacy of PrEP?

Most HIV organizations today will advise you that PrEP, if taken correctly in the form of a daily Truvada tablet, can reduce a person's risk of getting HIV by 90% or more. They will also caution users, particularly those at high risk, that the drug is not to be used in isolation but rather as part of an overall HIV prevention program (including condoms, limiting the number of sex partners, etc.)

But the message is often filtering down to the public is far different ways, with social media and news outlets frequently over-hyping or skewing the actual evidence.

Today it is not uncommon to hear that PrEP is "99% effective" in preventing HIV, or to see research sensationalized in order to declared that PrEP "100% effective" among high-risk gay men don't use condoms.

And while it is true that some studies among men who have sex with men (MSM) have reported no infections among those fully adhered to therapy, these kinds of results don't necessarily translate to real-world situations, where numerous confounders can significantly reduce the efficacy of PrEP an individual level.

It is many of these confounders that place the Canadian incident in a more telling light.

What Can Undermine the Effectiveness of PrEP?

In their research, the MLMC investigators suggested that the Canadian man was infected by an HIV-positive partner whose own antiretroviral therapy was failing. After genetic resistance testing, the partner's virus was shown to be resistant to both tenofovir and emtricitabine (the component drugs of Truvada), effectively cancelling out the protective benefit of PrEP. 

While some pundits have asserted that this type of multi-drug resistance is "rare"—with a prevalence of less than 1%—other research paints slightly a different picture. We know, for example, that tenofovir resistance currently runs anywhere from 20% (in Europe) to 57% (in Africa) among patients failing therapy, according to a 2016 report from the TenoRes Study Group.

In cases like this, even if the emtricitabine component were to remain viable, its ability to prevent infection remains, at the very best, low to negligible. This alone questions whether the conditions for infection in the Canadian case were necessarily "rare,” while highlighting the challenges faced by communities where tenofovir resistance rates run high.

Meanwhile, other confounders can potentially undermine the efficacy of PrEP. Chief among them:

  • The failure to achieve and maintain the adequate levels of Truvada in the bloodstream. While inconsistent dosing is most often the cause of these failures, it is also known that patients starting PrEP need to be on treatment for around 20-30 days before the drug can be considered effective. Once therapeutic drug levels are achieved, occasional missed doses become less of an issue—at least in gay male populations.
  •  A disparity in the effectiveness of PrEP in gay men versus heterosexual women. There is now also evidence to suggest that PrEP may not be as effective in women, and that even with complete, uninterrupted adherence, the protective benefit may fall well below the 90% threshold seen in gay men.

    In their totality, these facts suggest two things: that the effectiveness of PrEP in some populations will be far lower than in others, and that the need for condoms and other preventive interventions remain as relevant as ever.

    With that being said, the efficacy of PrEP does not appear to be inherently diminished by many of the traditional risk factors associated with infection. While inconsistent condom use and multiple sex partners, for instance, are known to increase the potential for HIV, they don't necessarily mitigate the effectiveness of PrEP in high-risk individuals.

    In fact, among gay men seen to be among the highest level of risk, the use of PrEP is still associated with an estimated 82-86% protective benefit over counterparts who don't use PrEP. The benefit is only seen to increase in those who dose consistently, who use condoms regularly, and who limit their number of sex partners (particularly those of unknown status or treatment status).

    So while PrEP was never intended to be the "magic bullet" that some had hyped it to be, it remains an invaluable tool in not only preventing HIV infection on the individual level, but potentially reversing infection rates in many high-prevalence communities.


    POZ Magazine. "PrEP Fails in Gay Man Adhering to Daily Truvada, He Contracts Drug Resistant HIV." February 25, 2016.

    New York Times. "Is Truvada, the Pill to Prevent H.I.V., 99% Effective? Don’t Be So Sure." July 17, 2014.

    Fox News. "HIV prevention drug 100% effective, latest research suggests." September 4, 2015.

    The TenoRes Study Group. "Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study." Lancet Infectious Diseases. January 28, 2016; published online; DOI: 10.1016/S1473-3099(15)00536-8.

    Molina, J.; Capitant, C.; Spire, B.; et al. "On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection." New England Journal of Medicine. December 1, 2015; published online in advance of print; DOI: 10.1056/NEJMoa1506373.

    UK PROUD Trial Steering Committee. "PROUD study interim analysis  finds pre- exposure prophylaxis (PrEP) is highly protective against HIV for gay men and other men who have sex with men in the UK." London, England; press release issued October 16, 2014.

    Cottrell, M.; Yang, K.; Prince, H.; et al. "Predicting effective Truvada PrEP dosing strategies with a novel PK–PD model incorporating tissue active metabolites and endogenous nucleotides (EN)." HIV Research for Prevention Conference. 28-31 October, 2014; Cape Town, South Africa; oral abstract 22.06 LB.

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