How does it work?
Did you know that there is a medication available to help prevent you from developing HIV? Probably not. Given how devastating the disease used to be and how life altering it still is, one would think that this ability to prevent the transmission of the virus would be a wide known fact. Why isn’t? Is the medication really effective? If so, what can be done to increase awareness?
The earliest known human case of a HIV-1 infection (the most predominant strain of HIV in the world) was found in 1959 in a blood sample of a man from Kinshasa, Democratic Republic of the Congo. While it is unclear how he became infected, in 1999, scientists discovered a subspecies of chimpanzee in West Africa that have the chimpanzee version of the immunodeficiency virus, known as the simian immunodeficiency virus (SIV). They feel that it was most likely was transmitted to humans because it’s common practice in the region to hunt these chimpanzees for food. During this process, humans would have come into contact with the chimpanzees infected blood. Over time, the virus mutated into HIV and became the source of HIV infection in humans. When looking at the genetic analysis of the human blood sample, it has shown that HIV-1 most likely stemmed from this single virus in the late 1940s or early 1950s. As time passed, the virus slowly expanded across Africa and into other parts of the world. The virus showed up in the United States sometime in the mid- to late 1970s. This is evidenced by the fact that from 1979 to 1981 rare types of pneumonia, cancer, and other illnesses were being reported by doctors and these conditions aren’t usually found in people with healthy immune systems. In 1982, the term “acquired immunodeficiency syndrome,” or AIDS, was used for the first time to describe the occurrence of opportunistic infections and formal tracking of AIDS cases began in the United States. By 1983, scientists realized that the HTLV-III/LAV (human T-cell lymphotropic virus-type III/lymphadenopathy-associated virus) was the cause AIDS. Later, the name of the virus was changed to HIV (human immunodeficiency virus). Since the first appearance of HIV/AIDS, it has infected 70 million people with 35 million of those dying. Currently, about 37 million out of the 7.65 billion people who are living around the globe are infected with it. An estimated 1.2 million Americans have it with 1 out of 8 of these people not knowing that they do. Globally, about 5,000 new infections occur daily.
Since the emergence of HIV, there have been great strides in treating it. One of these was a medication called Truvada, which is actually the combination of two medications (tenofovir and emtricitabine). It was introduced to the market in 2004. In 2012, the Food and Drug Administration (FDA) approved it for being use as Pre-Exposure Prophylaxis (PrEP) to keep high risk HIV negative people from becoming infected. It was initially approved for those 18 years old and above, but in 2015, the FDA changed that guideline to include HIV-negative adolescents weighing at least 35 kilograms, or approximately 77 pounds. It is essential to note that PrEP is different from PEP (post-exposure prophylaxis), which is an option for someone who thinks they’ve recently been exposed to HIV during sex or through sharing of needles. PEP means taking antiretroviral medicines after a potential exposure to prevent becoming infected. It must be started within 72 hours of the possible exposure and be taken once or twice a day for 28 days.
Truvada works by staying in your body’s T cells, which is one of the several types of immune cells. The T cells are the same cells that HIV targets. So, when there are enough of the drug molecules in the cells, they can stop the virus from replicating and stop the infection before it can gain hold. This concept is very similar to malaria-prevention pills. For example, if you are going to a place where malaria is prevalent, your doctor would prescribe medications for you to take before and during your trip in order to make it harder for the infection to take hold. Unlike vaccines, your body doesn’t develop long-lasting immunity because you’re only protected while taking the medication. This is also true with Truvada, which is why you need to take the pill daily in order to be protected.
The FDA has specific recommendations as to who should take PrEP. They state that it should be used by people who are HIV-negative and in an ongoing sexual relationship with an HIV-positive partner, anyone who isn’t in a mutually monogamous relationship with a partner who recently tested HIV-negative, any gay or bisexual man who has had anal sex without using a condom or have been diagnosed with an STD in the past 6 months, any heterosexual men or women who don’t regularly use condoms during sex with partners of unknown HIV status (especially those who are at substantial risk of HIV infection, like people who inject drugs or women who have bisexual male partners). The FDA also recommends PrEP if you’ve injected drugs, have shared needles or been in drug treatment in the past six months. In addition, PrEP can help protect you and your baby from getting HIV infection if you’re trying to get pregnant, during pregnancy or while breastfeeding. If you are using PrEP for this purpose, you need to use the medication daily for at least three weeks before you can achieve maximum protection. For maximum protection for receptive anal sex takes at least seven days of daily use; whereas, maximum protection for receptive vaginal sex and injected drug use is achieved after 20 days of daily use. It’s currently unknown how long it takes to reach maximum protection for insertive anal or vaginal sex. In any scenario, you must take an HIV test prior to starting the pill to ensure that you don’t already have it. After starting the pill regimen, you must see your doctor every three months to have additional HIV tests to verify that you haven’t become infected. As far as side effects, no serious ones have been found. The ones, like nausea, aren’t life threatening and typically go away over time. Some patients did see a drop in their bone density, but it hasn’t led to an increase in bone injuries. The good news is that regular bone strength returns if you stop taking the medication. In extremely rare cases, liver complications have occurred. These are also things that your doctor will monitor at your three month follow-ups.
Since no long-term harmful health effects have been discovered, PrEP has definitely been shown to be safe and effective. If taken daily, it reduces the risk of getting HIV from sex by more than 90% and by more than 70% for people who inject drugs. Two major studies help demonstrate this success. In a study of 2,499 HIV-negative men and transgender women who have high-risk sex with men, those who took Truvada had 42% fewer HIV infections than those who did not. Another study had 4,758 heterosexual couples in which one member was infected with HIV and one was not. The study showed that PrEP reduced the risk of HIV infection by 75%. Due to this level of effectiveness, the Centers for Disease Control (CDC) and World Health Organization (WHO) now recommend it as a valuable way to prevent HIV infection among those who are at high risk. Several reports in the Journal of the American Medical Association (JAMA) of Internal Medicine show that providing PrEP to men who have sex with men, which the group at highest risk, had a significant decrease in their rates of HIV. Since it was first approved in 2012 until 2016 (the most recent year for data comparison), there has been an 880% increase in PrEP users. However, just five states, New York, California, Florida, Texas and Illinois, account for nearly 50% of these users. In 2016, the south accounted for more than half of all new HIV diagnoses, but it only accounted for just 30% of all PrEP users. There are also demographic disparities. According to an analysis done by the CDC of 2015 data, 44% of African Americans and 25% of Latinos could have potentially benefited from using PrEP, but only 1% of that African American population and 3% of that Latino population were actually prescribed it.
Since we know that nothing is 100%t effective, it should come as no surprise that health officials have confirmed that there have been six failures of PrEP with four of the six involving rare, resistant HIV strains. In all cases, the patients were switched to new HIV medications and responded quickly to the treatment, which has resulted in them becoming HIV-undetectable shortly after switching medications. While Truvada isn’t fail-proof, it’s still nearly 100% effective, which is incredible when you consider that yearly there are millions of new HIV cases across the globe and tens of thousands of those occur in the US alone. According to the CDC, condoms are only effective at stopping about 80% of HIV infections, whereas, PrEP is effective at stopping about 90%. However, when condom failures occur, we don’t say to stop using condoms, so why would it be a good idea to tell people to stop using PrEP when there are failures? The problem is that unlike condom failure, PrEP failure makes the news. It’s important to note that using PrEP doesn’t mean that you should stop using condoms because it doesn’t give you protection against other STDs, like gonorrhea, chlamydia, genital warts and herpes.
While HIV has been part of our lives since the 1970s, we still have trouble discussing its prevention, especially when we are in an intimate relationship. This lack of discussion can bring unnecessary anxiety into the relationship. Often, people taking PrEP, or those considering whether or not to take it, are concerned about what their friends, family and potential partners will think of them. Some gay men are comfortable with their sexuality and don’t have guilt around it, so for them taking PrEP seems as normal as using condoms. For gay men who aren’t comfortable with their sexuality, the idea of PrEP is uncomfortable. Additional issues are cultural perceptions about HIV and HIV treatments, mistrust of the medical system and opposing social or health priorities that play a role in a lower adherence to the drug regimen. Since the FDA expanded the use of PrEP to include adolescents who weigh at least 77 pounds, it has created another barrier because many adolescents are still under their parents’ insurance and might want to access PrEP, but would have a challenging time getting it without their parents knowing about it. PrEP also suffers from an image problem because many people feel that if someone is taking it, then they are more likely to be promiscuous. The most concerning problem regarding PrEP is that people aren’t aware it exists. All of these things need to be addressed in order to make PrEP available to those who need it the most.
This lack of understanding surrounding PrEP isn’t just limited to consumers, but is abundant among insurance companies. Many are unaware that it has dual indications for both the treatment and prevention of HIV. Some insurance companies have gone so far to deny people coverage if they were taking PrEP as a prevention technique. Despite this misconception by some companies, the cost of it is covered by many health insurance plans, which is vital since the monthly price tag is about $1600. One issue is that there are different level of co-pays, so it can still result in a hefty monthly pill for the patient. Thankfully, for those with limited or without insurance, a commercial medication assistance program provides free PrEP to people who need it. On average, it costs somewhere between $8,000 to $14,000 a year to take PrEP. When you consider that lifetime HIV treatment costs between $375,000 and $400,000, it’s easy to see that PrEP is much more affordable. For most people, if they were to be diagnosed with HIV and a doctor said here’s a pill that will keep you from dying, they’d probably be more willing to pay for that pill than they are to pay for a pill that will prevent them from getting the disease in the first place. This is why we need to continue to educate people on their risk. Yet, some people decide to stop taking PrEP. They might do this because the risk of getting HIV becomes lower due to changes in their life, they don’t want to take a pill every day, often forget to take their pills or they have side effects from the medicine that are interfering with their life. A major concern with people who don’t take pills daily is that they’ll get infected and the HIV strain will end up with resistant to the medications, which means this resistant strain could be passed to other people. To help make it easier for people to stick with a PrEP regimen, researchers are working on other forms, including injections, intravaginal rings and implants, but these are still several years away from being available.
In an effort to raise awareness about PrEP, Gilead (the manufacturer of Truvada) has started several endeavors. From June through August of 2018, they had a television ad campaign hoping that it would inspire open and honest discussions about sexual health and elevate public awareness of HIV prevention. In September 2018, they increased the annual benefit they offer for Truvada to $7200 from the original $4800. Also, for those who qualify for the medication assistance program, they are eligible to receive the benefits for 12 months, instead of the original 6 months that had been offered. Gilead isn’t the only one trying to make sure that PrEP is available. An increasing number of state health departments have also unveiled PrEP drug assistance programs using state funding to make it available for those who otherwise don’t have access to it. The unfortunate thing is that often patients aren’t aware of these assistance programs.
Despite all of these programs, the only one way that PrEP will work is if people see their doctors and their doctors actually ask them about their sex lives. With the FDA approval for PrEP comes their guidelines for a risk-reduction program. They state that the use of PrEP should include discussion of safer-sex practices, counseling, HIV testing and it should not be used alone for HIV prevention. Due to these guidelines and the belief that if people are taking PrEP they will engage in riskier behavior, some doctors don’t prescribe it. In reality, there are a lot of people who don’t use condoms anyway and the drug doesn’t make users more promiscuous or more reckless about their risk. We have to be realistic about what is really going on.
There is no question that prescribing PrEP requires a strong doctor-patient relationship and the role of the family physicians is playing in increasing role in the awareness and use of PrEP. This will continue because primary care physicians are likely be the doctors who provide care to most of these uninfected patients who are at risk for HIV. In order to help doctors with this process, the staff in the Department of Family & Community Medicine at the University of California, San Francisco and provides free, expert advice via their PrEPline. They help doctors as they decide who might benefit from PrEP, how to prescribe it, knowing the protocols for follow-ups to ensure safe use of the medication and how to identify new transmissions. The hotline can be reached by calling 855-448-7737 from 11 a.m. to 6 p.m. EST, Monday through Friday.
In order to help spread the message to doctors, a group of independent experts was convened by the government called the US Preventive Services Task Force (USPSTF). Many professional organizations follow the advice that is set forth by the USPSTF. In order to come up with their recommendations, the task force analyzes all the available evidence, including several large studies looking at specific groups of people at high risk of infection that showed PrEP could lower the risk of the healthy partner from becoming infected with HIV by up to 90%. They gave PrEP the highest grade the task force awards for the quality and strength of the evidence. Their recommendation is that people at high risk of acquiring HIV infection be prescribed PrEP. Also, they recommend that all teens and adults between the ages 15 to 65 and pregnant women, be screened for HIV. This supports the current guidelines by the CDC that have been in place since 2014. The purpose of their recommendation is to help break down the barriers of resistance.
PrEP is just one small component of a much larger HIV prevention plan. There is no individual intervention is going to get rid of HIV. We need to approach the problem from many different perspectives. According to the National HIV/AIDS Prevention Strategy for the United States, there are several areas that we should be focusing on in the next few years. One of them is promoting full access to PrEP. The others are making sure HIV testing is widespread in order to enable early treatment for infected patients and providing support to people living with HIV so they can continue to receive care over their lifetime. By doing all of these things, we’ll be closer to achieving universal viral suppression. In order to have the best chance of this, we need to put aside concerns that a drug-based prevention strategy for HIV will lead to more unsafe behavior and higher HIV rates. The development of PrEP is the first medical intervention we’ve had to prevent HIV in the entire history of the epidemic. Unfortunately, of the estimated 1.1 million Americans who would benefit from PrEP, only about 250,000 are taking or have taken the medication. Preventing new HIV infections is a critical part of a comprehensive strategy in controlling the epidemic because if more people are protected from infection, then fewer people can spread the virus to others. We are at the cusp of a time period that will be looked back on a critical moment in the fight against the spread of HIV…what an awesome place to be!