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It’s been only a few short decades since scientists identified acquired immunodeficiency syndrome (AIDS) and the virus that causes it, human immunodeficiency virus (HIV). Since HIV was discovered in the early 1980s, it has been transformed from a disease that killed people within months to years of diagnosis to a very manageable chronic disease. In so doing, the treatment of HIV has become one of the greatest successes of modern medicine. People with HIV who have access to proper medical care live quite normal lives provided that they take their medication faithfully and stay plugged in with their healthcare providers.
However, HIV is still a significant public health issue. Approximately 1.1 million people in the US are living with HIV, according to the Centers for Disease Control and Prevention (CDC), and about 14% of them have never been diagnosed (CDC-a, 2019). At the time of this writing, under two-thirds of people with HIV were receiving HIV care, and only about half had full viral suppression (undetectable levels of the virus in their blood) (HIV.gov, 2019). This means that around half of all people living with HIV in the US are at risk of having complications from HIV, including developing AIDS.
As good as HIV treatment has become, strategies to prevent its spread are extremely important. Methods of prevention include (CDC-b, 2019):
- Limiting the number of sexual partners
- Safe sex using barrier methods, including latex and polyurethane condoms and dental dams
- Viral suppression in those who already have HIV prevents transmission to their sexual partners
- Viral suppression in pregnant women with HIV
- Avoiding breastfeeding in women with HIV
- Avoiding injection drug use or using sterile equipment if you do inject drugs
- PrEP and PEP
What is pre-exposure prophylaxis or PrEP?
Certain groups are at particularly high risk of acquiring HIV due to various factors. For these groups, there is a highly effective HIV prevention strategy called pre-exposure prophylaxis or “PrEP” for short. PrEP involves taking a drug called Truvada daily to prevent HIV. Truvada contains two antiretroviral medications (emtricitabine/tenofovir disoproxil fumarate.) It is often used as part of a complete HIV treatment regimen for those already diagnosed with HIV (complete HIV regimens are usually three drugs or more). When taken daily, PrEP can reduce the risk of HIV transmission through sexual contact by about 99%.
On October 3, 2019, the United States Food and Drug Administration (FDA) approved a second drug for PrEP called Descovy (FDA, 2019). Descovy has the same two drugs as Truvada, but the tenofovir disoproxil fumarate (TDF) comes in a different form called tenofovir alafenamide (TAF). TAF is considered to be safer for the bones and kidneys than TDF. At the time of this writing, Descovy is approved for PrEP in men and transgender women, but it is not approved for HIV prevention for receptive vaginal sex.
PrEP vs. PEP: What’s the difference?
You may have heard of something called “PEP,” which sounds a whole lot like PrEP, so what is PEP, and how is it different from PrEP? PEP stands for post-exposure prophylaxis, and it is different from PrEP in a few critical ways (CDC-c, 2019).
PEP is given to people after they have an exposure that puts them at high risk for contracting HIV (CDC-c, 2019). Some examples include:
- Potential exposure to HIV during sex (e.g., a broken condom with a partner who is HIV positive or whose status is unknown),
- Cases of sexual assault
- After sharing needles or other injection drug use paraphernalia
- Healthcare workers who experience an accidental needle stick with a needle that was used on someone who is HIV positive or has unknown HIV status
This is the first significant difference between PrEP and PEP. While PrEP is a proactive form of HIV prevention, PEP is reactive and is used after a high-risk exposure occurs. PEP must be given within 72 hours of the exposure to be effective, and it is continued for 28 days. This also differs from PrEP, which is used continuously as long as the high-risk exposure continues. Another major difference between PrEP and PEP is the medications that are used. Truvada, which is not a complete regimen for those diagnosed with HIV, is used for PrEP, but PEP requires a complete HIV drug regimen with three or more drugs. The most important thing to remember is that PEP is not meant to be used by people who regularly engage in behavior that puts them at high risk for HIV. In these cases, PrEP is recommended.
|Taken before possible exposure to HIV||Taken after possible exposure to HIV (must be started within 72 hours to be effective)|
|Consists of 2 antiretroviral medications in one pill||Consists of 3 antiretroviral medications|
|Taken daily (reaches maximum protection after 20 days) or on-demand (off-label use)||Taken daily for 28 days|
|99% effective at reducing HIV transmission through sexual activity when taken properly||Efficacy varies|
|Recommended for regular use||Not recommended for regular use|
Truvada vs. PrEP: Are they the same thing?
Many people think that Truvada and PrEP are the same thing, but this is not the case. Truvada is simply the combination of two HIV drugs. It has different uses, only one of which is PrEP. Truvada is also a component of some complete regimens for people already diagnosed with HIV, and Truvada is also part of recommended PEP regimens for those who have had a high-risk exposure.
- Can be used for PrEP
- Can be used as part of PEP
- Can be used as part of treatment for those with HIV
- Truvada is a 2-drug regimen that was approved for PrEP in 2012
- Descovy is a 2-drug regimen that was approved for PrEP in 2019 except for in those engaging in receptive vaginal sex
- Other medications are currently being studied and may be used for PrEP in the future
Journey to FDA approval
The FDA initially approved TDF for the treatment of HIV-1 in combination with other medications in 2001 (FDA, 2018). TDF alone is branded as Viread, and it was the first type of medication known as a nucleotide analog to be approved for treatment. The FDA initially approved emtricitabine for the treatment of HIV-1 in combination with other medications in 2003. Emtricitabine alone is branded as Emtriva and is a type of medication known as a nucleoside reverse transcriptase inhibitor.
In 2004, the FDA approved the combination of TDF and emtricitabine in a single pill branded as Truvada. This combination allowed for a more straightforward dosing regimen for patients who were taking both drugs for the treatment of HIV.
Eight years later, in 2012, Truvada was approved for PrEP thanks in part to the results of two clinical trials that demonstrated the safety and efficacy of using the medication for HIV prevention (AIDSinfo, 2012). The iPrEx study evaluated the effectiveness of Truvada in men and transgender women who have sex with men, while the Partners PrEP study assessed the efficacy of Truvada in heterosexual couples where one partner was HIV-positive, and one partner was HIV-negative.
Who is PrEP for?
According to the CDC, PrEP is recommended for the following groups who are at high risk of acquiring HIV.
- Men who have sex with men (MSM) who are not in monogamous relationships with an HIV negative partner and have had unprotected anal sex (top or bottom) or a bacterial sexually transmitted infection (STI) such as syphilis, gonorrhea, or chlamydia in the past six months.
- Heterosexually active men and women (MSW or WSM) who are not in a monogamous relationship and don’t use condoms consistently with one or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (MSM or IVDU)
- Heterosexually active men and women who are in a monogamous relationship with an HIV-positive partner (also known as a serodiscordant couple)
- Injection drug users who have shared needles or other drug use paraphernalia in the past six months
How effective is PrEP?
According to the CDC, PrEP decreases the risk of acquiring HIV from sex by 99% and from injection drug use by 74% if it is taken daily (CDC-d, 2019). This makes PrEP an extremely effective tool in preventing the spread of HIV in addition to other prevention methods listed above.
PrEP is intended to be taken every day. If you miss one or more doses, PrEP will not be as effective at preventing HIV. It is also not maximally effective right away. It takes approximately seven days of use for PrEP to be maximally effective at preventing HIV during receptive anal sex. It takes about 20 days of use for PrEP to be maximally effective at preventing HIV during receptive vaginal sex or injection drug use. It is unknown how long it takes for PrEP to be maximally effective during insertive anal or vaginal sex.
New research is looking into the efficacy of Truvada if taken on-demand (NYC Health, 2019). Taking Truvada on-demand means taking two tablets 2–24 hours before sex, then one pill 24 hours after the first dose and one tablet 48 hours after the first dose. Altogether, this involves taking four tablets in 48 hours. The IPERGAY study found that taking Truvada on demand reduces the transmission of HIV through sexual contact by 86% in MSM. And no transmission was seen in another study called Prevenir. People who the on-demand method might be right for include:
- People who have long periods of sexual inactivity
- People with kidney problems
- People who inconsistently use condoms during sex
- People who cannot afford PrEP and want to take fewer pills
- People who otherwise do not want to take a daily medication
While it may be more appealing to take PrEP on demand rather than daily, some people may find it easier to take a pill at the same time every day as part of their daily routine than to remember to take doses around sexual activity. Additionally, taking medication daily is currently the only FDA-approved method for PrEP. Taking the medication on-demand is an off-label use of the drug.
What are the side effects of PrEP?
PrEP is safe for most people, and few people who begin Truvada for PrEP have to stop using it due to side effects. The most common side effects in PrEP studies that occur more frequently than placebo are headaches (7%), abdominal pain (6%), and unintentional weight loss (3%) (FDA, n.d.). Other potential side effects include worsening kidney function and decreased bone density. See the Truvada prescribing information for a full list of potential Truvada side effects.
Testing for hepatitis B virus, HIV, and kidney function should be completed before starting PrEP with ongoing HIV and kidney function testing. PrEP should never be used in someone who is HIV positive. These individuals require a full HIV treatment regimen, usually with three or more HIV medications. There is a risk of the virus developing drug resistance if PrEP is used alone in someone with HIV.
Who has access to PrEP?
Any primary care provider can prescribe PrEP. However, some providers may be unfamiliar with PrEP and may not be willing to prescribe it. Your best bet is to ask your provider about PrEP, and if they say no, ask them to refer you to somebody who will prescribe it. Taking Truvada also requires having a blood test done every three months to check kidney function and HIV status, so to be on Truvada, you have to be willing and able to undergo this testing.
For those who are unable to find a PrEP provider in-person, some online applications prescribe PrEP on their platforms after a telemedicine interaction with a licensed provider. In some cases, the blood test can also be mailed to your home, further reducing barriers to getting the medication.
On its own, Truvada can be extremely expensive. However, with health insurance, this cost can be significantly reduced. Gilead (the company that makes Truvada) also offers a co-pay card, which further reduces the cost—often to $0 (Gilead, n.d.). And some states (such as New York) have medication assistance programs that lower the cost of the medication for those without insurance (NYC Health, 2018). In fact, in many cases, Truvada is completely free when the right resources are utilized.
The point is, the ability to see a healthcare provider in person and cost should not be barriers to taking PrEP. Anybody who wants to be on PrEP and does not have any contraindications to its use should be able to access it.
Does PrEP increase sexual risk-taking?
One of the concerns about the widespread use of PrEP is that people may increase high-risk sexual behaviors because of the protection PrEP offers against HIV. The research on this has been conflicting, with earlier studies showing no increased risk-taking (Liu, 2013). However, a more recent study on MSM in Australia showed decreasing condom use as PrEP use increased in the studied population (Holt, 2018).
It’s important to remember that PrEP does not protect against other STIs, such as gonorrhea, chlamydia, and syphilis. While there may be an increase in risky sexual behavior with PrEP use, its role in preventing the spread of HIV is a critical public health initiative, and recommendations for PrEP use remain the same even with this new data. People who use PrEP should be educated on the risks that remain with the use of PrEP.
If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.
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- Liu, A. Y., Vittinghoff, E., Chillag, K., Mayer, K., Thompson, M., Grohskopf, L., et al. (2013). Sexual Risk Behavior Among HIV-Uninfected Men Who Have Sex With Men Participating in a Tenofovir Preexposure Prophylaxis Randomized Trial in the United States. JAIDS: Journal of Acquired Immune Deficiency Syndromes, 64(1), 87–94. doi: 10.1097/qai.0b013e31828f097a. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23481668
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- NYC Health. (2019, June). “On-Demand” Dosing for PrEP: Guidance for Medical Providers. Retrieved from https://www1.nyc.gov/assets/doh/downloads/pdf/ah/prep-on-demand-dosing-guidance.pdf
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- U.S. Food and Drug Administration (FDA). (2018, January 5). HIV/AIDS Historical Time Line 2000 – 2010. Retrieved from https://www.fda.gov/patients/hiv-timeline-and-history-approvals/hivaids-historical-time-line-2000-2010
Dr. Mike is a licensed physician and the Director, Medical Content & Education at Ro.