How Effective Is PrEP at Preventing HIV?

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Pre-exposure prophylaxis (PrEP) medications Truvada and Descovy are taken daily to prevent human immunodeficiency virus (HIV) in HIV-negative people who are considered at high risk for infection.

When taken as prescribed, PrEP can reduce the risk of getting HIV from sex by more than 90% and from injection-drug use by more than 70%.

Bottles of antiretroviral drug Truvada are displayed at Jack's Pharmacy on November 23, 2010 in San Anselmo, California.
Justin Sullivan / Getty Images News / Getty Images

This article will explore exactly who PrEP is intended for, each PrEP medication, and factors that may support or reduce their effectiveness.

Who PrEP Is For

Anyone can get HIV. Your sex, age, sexual orientation, race, and ethnicity do not independently factor into your risk.

PrEP is for those considered to be a high risk of HIV. Reasons that put you at high risk include:

  • You have a sexual partner with HIV or whose status is unknown
  • You do not consistently use condoms
  • You have sex in a region or network in which HIV is common
  • You have been diagnosed with a sexually transmitted infection (STI) in the past six months
  • You have a drug-injecting partner with HIV
  • You share needles, syringes, or other equipment, such as cookers, to inject drugs

PrEP can be used by women trying to get pregnant or who are pregnant or breastfeeding and have a partner with HIV.

PrEP Medications

There are two PrEP medications approved by the Food and Drug Administration (FDA) for use in adults and adolescents. One may be recommended over the other depending on your risk behaviors and health profile.

Both are prescription combination medications taken in a once-daily tablet:

  • Truvada (emtricitabine and tenofovir disoproxil fumarate): Recommended for anyone at risk of HIV through sex or drug use; a generic version is also available
  • Descovy (emtricitabine and tenofovir alafenamide): Recommended for those at risk of HIV through anal or oral sex, but vaginal; not used in those assigned female at birth

Recap

Before deciding for yourself that you are not at high risk for HIV, remember that this is dictated by your behaviors, not your background.

If your doctor determines you are at high risk, Truvada or Descovy may be recommended depending on whether or not you have vaginal sex, inject drugs, or were assigned female at birth.

Real-World Efficacy of PrEP

Some studies among high-risk gay men have reported no infections among those fully adhered to therapy. Among gay men considered the highest level of risk, the use of PrEP was associated with an estimated 86% protective benefit over counterparts who don't use PrEP.

These results are promising but may not translate to real-word scenarios where numerous factors, including behaviors or rare strains of virus, may reduce the efficacy of PrEP on an individual level.

The main factors that can significantly reduce the efficacy of PrEP include:

  • Inconsistent dosing: Skipping doses means you may not maintain high enough levels of the drug in your bloodstream.
  • Not using other protective measures when starting PrEP: It takes seven days for PrEP to reach maximum effectiveness against anal transmission; that window pushes out to 21 days for vaginal transmission and injection-drug use.

It takes longer to establish an adequate level of protective enzymes in vaginal tissues than in anal and rectal tissue.

PrEP-Resistant HIV

It was widely reported in 2016 that a man taking the HIV prevention drug Truvada contracted the virus despite being fully adherent to the once-daily drug regimen.

The news raised serious concerns among some as to how effective the strategy actually is at ensuring that an HIV-negative person remains 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 Truvada. A review of both pharmacy records and the patient’s blood tests that measure drug concentrations showed that drug was taken as prescribed.

Genetic testing eventually revealed that the man had acquired a rare mutated strain of HIV that was resistant to the two individual drug agents that comprise Truvada. This effectively cancelled out the drug's protective benefit.

A 2019 study in the journal Drugs looked at drug resistance found four additional case reports of people acquiring HIV while taking PrEP consistently. Three of those four people also had strains of HIV that were resistant to both drug agents.

In one case, researchers found the person had wild-type HIV, which means there were no HIV-resistant mutations of any sort. (Most people are initially infected with wild-type HIV, or HIV in its natural state.)

PrEP-resistant HIV is still considered rare. For example, in 2018, University of Washington researchers did thousands of genetic sequence tests. They estimated that between 0.4% and 0.6% of the 6,798 people living with HIV in Kings County, which includes Seattle, had both a detectible viral load (HIV found in blood) and a strain of HIV resistant to tenofovir and emtricitabine.

Among patients failing therapy, studies suggest tenofovir resistance runs anywhere from 20% (in Europe) to 57% (in Africa), according to a 2016 report from the TenoRes Study Group. In cases like this, the emtricitabine component in PrEP may not be enough to prevent infection.

It's possible that the effectiveness of PrEP in some populations may be far lower than in others, but more research is needed.

Recap

PrEP reaches maximum effectiveness after seven days for anal sex and 21 days for vaginal sex or injection-drug use. Skipping doses or failing to use additional protective measures until you reach these points makes PrEP much less effective.

There are rare strains of HIV that are resistant to PrEP, though this is rare.

PrEP and Multiple Sex Partners

The efficacy of PrEP does not appear to be inherently diminished by many of the traditional risk factors associated with infection in most cases.

While inconsistent condom use and multiple sex partners, for instance, are known to increase the potential for HIV, they don't seem to mitigate the effectiveness of PrEP in high-risk individuals.

However, this is not proven and more research is needed.

The case of the person who contracted a wild-type HIV while on PrEP was part of a European PrEP study. The man took the medication as prescribed, which was confirmed through blood tests.

He reported over 90 sex partners and over 100 acts of condom-less anal sex during the 12-week trial. While on PrEP, the man was diagnosed twice with rectal gonorrhea and once with rectal chlamydia.

Given his record of taking the medication, some researchers suspect that the medication may have been overwhelmed by very high levels of exposure to HIV or other factors, such as having other STDs when exposed to HIV.

If so, these still-unidentified factors may place others at risk. Until researchers know more, safer sex practices, such as using condoms, should be adhered to if only to provide an additional layer of protection.

This added protection is particularly important if you don't know whether or not your partners were tested for HIV, or if they have HIV but you're unsure if they're being treated with medication.

HIV drugs can reduce viral load, which is the amount of HIV in their blood. A high viral load increases the likelihood of spreading HIV.

In addition, PrEP does not protect you against other types of sexually transmitted infections.

Recap

PrEP still cannot be considered a "magic bullet" that somehow negates the benefits of other forms of protection, such as condoms. It is important that you continue to practice safer sex while taking PrEP.

Summary

PrEP can reduce the risk of getting HIV from sex by more than 90% and from injection-drug use by more than 70%. If you miss doses, PrEP is much less effective.

There are two PrEP medications approved by the FDA, both of which are taken daily. Truvada can be used to reduce risk from sex or drug use. Descovy is only recommended for those at risk of HIV through anal or oral sex, and it is not for those assigned female at birth.

There are rare strains of HIV virus with mutations that make it resistant to PrEP. There may be other factors that also lower effectiveness. Additional protective measures, such as using condoms, can support PrEP and reduce risk of HIV.

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