Every first of December since 1988, the globe has recognized World AIDS Day. This annual event serves as a reminder of the global struggle to end HIV-related stigma, an opportunity to honor those we have lost and a rallying cry to continue working toward a day when HIV is no longer a public health threat.
There have been several key moments in the last 40 or so years that were genuine times to celebrate in the fight against HIV.
One of those key moments was on July 16, 2012 with the U.S. Food and Drug Administration’s approval of PrEP.
PrEP, or pre-exposure prophylaxis, is a medication that reduces a person’s chances of contracting HIV. It is a safe and highly effective drug when taken as prescribed.
The first drug approved by the FDA as PrEP was Truvada. This one-a-day pill was previously approved as part of an HIV treatment regimen but was found to offer uninfected individuals protection against the virus.
“If and when HIV infects the body, it has to incorporate genetic material into your cellular DNA and PrEP actually prevents that from happening,” says Dr. Steven Barnett, chief medical officer for CAN Community Health. “By taking this one pill every day you’ve essentially eliminated the risk of being infected with HIV.”
For years, Truvada was the only pill approved by the FDA to be used as PrEP, until 2019, when Descovy was approved for the same purpose.
“Descovy took away some of the issues that Truvada has,” Barnett says. “Truvada, which also has a generic available now, is still a very safe and effective drug but Descovy took away the concerns in some people who saw bone loss and Truvada can be a tad bit harder on the kidneys in some people.”
The issue with Descovy is it hasn’t been FDA approved for people assigned female at birth.
“They haven’t completed the studies for that but we think it is going to be fine once they do. But because of that we prescribe Truvada for those born female at birth right now,” Barnett adds.
With PrEP approved by the FDA and available to patients, who is the medication specifically for? Everyone, says Erick Suarez, nurse practitioner and chief medical officer for Pineapple Healthcare.
“PrEP is for literally anyone who has sexual contact who is 77 pounds or greater. It is actually weight based and not age based,” Suarez says. “Because PrEP is preventative and not treatment you also cannot give it to a minor without parental consent in the state of Florida.”
Suarez says that the initial trials for Descovy only being tested in people who were assigned male at birth turned out to have a silver lining.
“The plus side to them not expanding the Descovy trials is everyone in the HIV-prevention world noticed, so when we started testing other medications they saw that we need to have a broader sample set in our studies,” he says.
INJECTABLE PREP
When studies began for a PrEP injectable medication, they did just that and, in 2021, the FDA approved an injectable PrEP called Apretude — the brand name for the drug cabotegravir — for everyone. But why was the development of an injectable form of PrEP needed if the oral form was so effective?
Because of the injectable med’s long-term nature, Suarez says.
“Apretude is taken every two months after your first two injections,” he says. “So month one you do one injection, month two you do one injection and then after month two you do every two months.”
“There are many reasons why someone might want to choose Apretude over Truvada or Descovy, but the biggest one is convenience,” Barnett says. “People who have very busy schedules and have difficulty keeping up on pills will find getting a shot every two months might work out better for them.”
Convenience isn’t the only reason someone might elect to take the injectable over the daily pill. Both Barnett and Suarez suggested several reasons someone would prefer the injectable including individuals without a good housing situation which can lead to difficulties with daily regimens, fatigue in taking a pill every day and even the stigma that can come with taking PrEP.
One of the big reasons that the injectable is appealing for patients, Suarez says, is because many people on PrEP pills forget to take them.
“When I am speaking with a patient I give them permission to tell me when they have missed taking their pills. So instead of saying ‘Have you taken your pills every day?’ I say ‘How many times do you forget to take them?’ You give them permission to open up and talk about that,” he says. “That’s where we discover that daily compliance can be an issue, especially in the younger community where all they take is PrEP, there’s no other medications so it is very easy for them to forget because there aren’t other conditions they are treating.”
Compliance is a big issue when it comes to oral PrEP since just missing two doses can reduce the treatment’s efficaciousness to 55%.
“You are basically flipping a coin at that point,” Suarez says. “That’s not giving you the protection that you need if you are taking PrEP.”
One thing to consider if you are looking at switching your PrEP regimen from the daily pill to the bi-monthly shot is how you would need to get it. The current injectable PrEP available must be administered by a trained medical professional which means you are looking at more office visits with the injectable.
“The injection is an intramuscular injection, so you are 90 degrees darting right into the muscle,” Suarez says. “It is usually injected into your backside but, because some people do have butt implants, studies have been done with the thigh muscle and it works there as well.”
Barnett adds that receiving the medication has zero risks as long as it is being administered by a trained professional.
“First, it is very difficult to give yourself an intramuscular shot in the buttocks,” he says. “But doing it at home, even if you could tolerate giving yourself a shot that deep, you’ve got to make sure it isn’t going directly into the bloodstream.”
Getting the injection into the muscle and not into the bloodstream is extremely important because of how this medication works.
“It is an emulsion,” Barnett says. “It sits in the muscle where it is injected and it slowly releases it into the blood stream.”
Suarez adds that the injection is a milky like substance that is quite gentle going in.
“The solution creates this kind of clay and that’s how it dissolves slowly over two months,” he says. “It is perceptible to the patient but it is not perceptible to the outside world. You do not have a lump or a mark there but the patient can sometimes feel it there. We tell them if they do feel it then take that as a good sign that it is working how it is supposed to.”
This technology for injectable medications isn’t new, says Barnett.
“Probably the most commonly known of these types of medications is the birth control Depo-Provera,” he says. “That’s an injection that lasts for three months instead of taking a daily pill. It’s just a way that the drug is embedded into this solution that is very slow releasing.”
As with any medication there is a chance for side effects; however, both Barnett and Suarez say that for most people there are little to no side effects.
“We have seen very few issues and those issues are the typical ones you see with all injectables —soreness or redness at the injection site,” Barnett says.
According to the website of ViiV Healthcare, the company that manufactures Apretude, possible side effects can include fever, tiredness, muscle or joint pain, blisters, redness and swelling. It also warns against using Apretude if you take any of the following medications: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin or rifapentine. Be sure you share what medications you are taking when speaking with your health care provider about PrEP.
While injectable PrEP is the popular new kid on the block, there are still reasons that taking the one-a-day pill might be a better option for some people.
“The injectable isn’t for everyone,” Barnett says. “Some people just do not like injections. It isn’t a painful shot but we understand that some people just have a injection phobia. Something else to consider, you have to show up for your appointments for the injection. There is a window after your injection that you are protected and if you go beyond that window we can’t guarantee your protection. So you have to show up to the office for the injections.”
Along with possibly needing to take that extra time off work for the appointments, Barnett says that blood needs to be drawn and tested more frequently.
“With pills we usually require labs every three months, with the injectable it’s every two months,” he says. “So the time for that as well as the added cost of the office visits and the labs with copays and such is something to consider.”
The cost of the drug is something that will come into play when working to cover it with your insurance plan.
“I am actually one of the largest providers in Central Florida for injectable PrEP and it is kind of a 50/50 mixed bag,” Suarez says. “About 50% of insurances will cover it, the other half of our patients go through the patient assistance program through the drug manufacturer. So if insurance will not cover it or they are uninsured or don’t have access to insurance, we advise them to access it through the patient assistance program.”
Suarez adds that while the Affordable Care Act specifies PrEP is a preventive drug and needs to be covered, it doesn’t specify which type needs to be covered.
“It allows the insurance company to pick and choose which one is best for their policies and limit patients to one or the other,” he says. “One might say we covered the generic Truvada, we did our job and complied with the Affordable Care Act, our job is done. Yes, they are following the law and doing what they are supposed to, but by limiting their patients to just one type they are leaving behind a lot of people that could benefit from this drug.”
INJECTABLE HIV TREAMENT
PrEP isn’t the only form of treatment that has an injectable medication option now. In Jan. 2021, the FDA approved Cabenuva, an injectable, long-acting HIV treatment regimen.
“Cabenuva is actually two injectables and has proven to be extremely effective,” Barnett says. “Because it is two medications, they are administered one into each buttock.”
The regimen follows the same track as Apretude, with a pair of shots each of the first two months followed by a pair of shots every two months following that. The first of the two shots is actually the exact same medication taken as PrEP (that injection being 200 mg/mL of cabotegravir) with the second shot being 300 mg/mL of the drug rilpivirine.
“The same rule applies with injectable HIV treatment as with injectable PrEP, do not massage the area,” Suarez says. “Let that little clay mass develop there and we want it to dissolve ever so slowly over time. We tell patients do not mess with it, if you feel it there then look at that as a reassurance that it is working.”
Barnett says that just as with injectable PrEP, very few side effects have been observed in patients using the injectable HIV treatment.
“Pain at the injection site occurs in about 10% of those you have gotten it, but we find that even that goes away by the second or third injection,” he says. “Honestly, the current medications that we have now, both oral and injectable, are extremely safe and void of side effects. We also are not seeing the resistance like we used to see in the older medications.”
So why would someone who has had great results using oral HIV treatments switch to an injectable? The same reason someone would want the injectable PrEP, Suarez says: convenience.
“We are at a place now with managing HIV that many people who are HIV positive and take HIV meds are healthy enough that they have no other conditions and this is the only pill they take,” he says. “Also for a lot of people, HIV was not a positive thing that happened in their life. It has its own negative connotation and psychologically it takes them back to that moment every time they take the pill. So to have an injection every two months as opposed to taking a pill everyday means they can be triggered less by it.”
Suarez does add that someone newly infected with HIV will need to start with an oral HIV treatment before switching over to the injectable.
“The reason is their viral load needs to be below 50 before they can start the injectable,” Suarez says. “In fact most insurance companies will not approve the use of the injectable until there is proof the patient’s viral load is below 50.”
Viral load is the amount of HIV in a person’s blood. It is measured by how many particles of HIV are in a blood sample with the results being given as the number of copies of HIV per milliliter of blood — for example 50 copies/mL. According to the Centers for Disease Control and Prevention, Someone with HIV is at an “undetectable level” when they have less than 200 copies/mL.
“We have found that when a patient starts with the injectable, they have a very difficult time in getting to an undetectable status,” Suarez says. “The injectable treatments are wonderful when it comes to maintenance but having the bite to really lower the viral load from someone who is newly detected, not so much.”
The success of injectables used for HIV prevention and treatment has led to some medication advancements on the horizon. The most promising being the PrEP injectable Lencaprivir.
“It is a new class that we call capsid inhibitors,” Barnett says. “It lasts for six months with one subcutaneous injection. Preliminary studies show that it is just as effective in preventing HIV all by itself.”
A subcutaneous injection is a type of shot that is administered under the skin as opposed to the current intramuscular injection. That would mean the injection could be administered by the patient at their home.
“That’s the holy grail of PrEP. The patient can administer themselves and then they would just need to show up for their labs every six months,” Barnett says. “The hope is that it will be FDA approved within a year.”
“I definitely feel like with PrEP, long-acting injectables will become common and whoever has the longest lasting injectable will win the gold,” Suarez says. “But we have to wait and see what that will look like. For example, if you have an injectable PrEP that lasts for a year but leaves you with green welts then you probably aren’t going to care that it protects you for a year.”
As for HIV treatment, Bartnett says there are some possibilities of using Lencaprivir.
“It is currently approved only for use as part of an HIV treatment regimen in those who have drug resistance to other HIV meds,” he says. “Some studies are looking at developing another long-acting injection to go along with Lencaprivir for HIV treatment or possibly taking the Lencaprivir shot along with a long lasting pill that you would take once a month or something like that but that is still a ways off.”
For Suarez, he sees the future of HIV treatment going a different route.
“To be honest, I don’t see injectables being the future of HIV treatment,” he says. “What I see going on right now in science, if I had to predict where we are going in the future with HIV treatment, I would say HIV would look like an infusion. Like an IV drip infusion in the doctor’s office once or twice a year. You come in for a 30-minute appointment and they hook you up to the first medication, flush you out and hook up the second one and then you are on your way.”
Regardless of which treatment or prevention you choose, nothing will work if you’re not on it, Barnett says.
“We have three options for PrEP, two pills and one injectable, but you have got to be on something,” he says. “If you are HIV positive, we currently have about five options for the one-a-day-pills and one injectable option, and those are all amazing treatments that work really well.”
For more information on HIV prevention and treatment, you can visit Pineapple Healthcare at PineappleHealthcare.com or contact them at 407-553-6336. Visit CAN Community Health at CANCommunityHealth.org or contact them at 844-922-2777.
