Ten years after pre-exposure prophylaxis (PrEP) for HIV became available in the United States, it is still being underutilized. Not only are many patients unaware of PrEP as an option for them, but many physicians, nurse practitioners, physician assistants, and other health care providers don’t realize that offering and prescribing PrEP is an appropriate and important aspect of primary care.
PrEP is an “amazing opportunity” to engage in health care prevention behaviors and build effective therapeutic relationships with patients, according to Leandro Mena, M.D., M.P.H., director of the Division of STD Prevention at the Centers for Disease Control and Prevention (CDC). “Health care providers can really play a pivotal role in reducing stigma and integrating STI [sexually transmitted infection] and HIV prevention and sexual health into routine practice and creating a welcoming environment for people,” Mena says.
PrEP initiation and management fits very well into the primary care model that physicians already use, Mena explains. “PrEP is about really engaging people and making sure that they continue to be engaged so they keep on coming back on a regular basis every three months to get medication refills and … other screenings,” he says.
Prescribing PrEP requires first learning about PrEP options, what makes a good candidate for PrEP, and how to help patients make an informed decision. Clinicians who are new to learning about or prescribing PrEP don’t need to make any radical changes in the way they practice, explains Rupa Patel, M.D., M.P.H., a research associate professor of infectious disease at the Washington University School of Medicine.
She urges physicians not to avoid prescribing PrEP simply because they feel they don’t have all the recommended resources and protocols set up in their clinic. “You can have goals over time, like over the next three years you’ll start building in some good sexual health practices and referrals into your clinic,” Patel says. “But the worst thing you could do is delay a PrEP prescription and someone seroconverts in front of you. The ideal PrEP client is someone who’s going to seroconvert in six months.”
Available PrEP Regimens
Clinicians can approach discussing the various PrEP options similarly to the way they would approach discussing contraception, according to Dawn Smith, M.D., M.P.H., a medical officer with the Division of HIV/AIDS Prevention at the CDC. Several options exist, so clinicians should briefly describe each one and then talk further about the ones that most interest the patient. Several PrEP medications are in the pipeline and likely to receive approval in coming years, but the currently approved options include two oral and one injectable:
- F/TDF (emtricitabine/tenofovir disoproxil fumarate; Truvada) is a daily oral medication of 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate. F/TDF is recommended for adults and adolescents of any gender who weigh at least 35 kg (77 lb) and are at risk for HIV through sexual contact or injection drug use.
- F/TAF (emtricitabine/tenofovir alafenamide; Descovy) is a daily oral medication of 200 mg emtricitabine and 25 mg tenofovir alafenamide. F/TAF is recommended only for cisgender men and transgender women at risk for HIV through sexual activity or injection drug use. F/TAF has not been tested for efficacy in cisgender women or in preventing HIV transmission during receptive vaginal sex, so it’s not recommended for anyone who is at risk via receptive vaginal sex.
- Cabotegravir (Apretude) is a 600-mg intramuscular injection first given in two doses a month apart, and then in 600-mg doses every 8 weeks. Patients may opt to receive oral cabotegravir during a 30-day lead-in to ensure they can tolerate the drug, but this isn’t required. Cabotegravir is recommended for anyone weighing at least 35 kg who is at risk for HIV through sexual activity, including those who inject drugs.
Before you prescribe any of these, patients should have had a negative HIV test in the previous week and labs showing adequate kidney function, indicated by a creatinine clearance of at least 60 mL/min for F/TDF and at least 30 mL/min for F/TAF. Those with poor kidney function can take cabotegravir, but increased monitoring for adverse effects is recommended.
Contraindications
The only real hard and fast contraindication with PrEP, aside from having HIV, is that those with poor kidney function should avoid F/TDF. Those with a creatinine clearance between 30 and 60 mL/min should be on F/TAF instead, as long as they qualify for it. Even someone who is borderline with a creatinine clearance of 70 mL/min may want to opt for F/TAF “just because we know that they don’t have a lot of kidney reserve,” says Joanne Stekler, M.D., a professor of medicine in allergy and infectious disease at the University of Washington.
People at risk for kidney disease, such as those with high blood pressure or diabetes, may want to consider opting for F/TAF as well. People with poor kidney function who don’t qualify for F/TAF, such as cisgender women or anyone with a creatinine clearance below 30 mL/min, can opt for the cabotegravir injection.
PrEP is safe to use while pregnant and breastfeeding, and it can be prescribed to adolescents as long as they meet the minimum weight limit.
Payer Often Determines Options
A patient’s preference, medical history, and comorbidities are considerations in assessing which options may be most ideal for them. But often the decision has to start with how the medication will be paid for, according to Stekler.
“When I’m talking with people, the first thing that we’re going to do is talk about insurance,” Stekler says. Medicaid or another public insurance will usually only pay for generic F/TDF, unless the patient has a contraindication, such as poor kidney function, a diagnosis of osteoporosis, or a history of not being able to tolerate F/TDF.
“For someone who’s using the medication assistance program,” in which the pharmaceutical company offers the drug at a discount, “I do a joint decision-making process with people because the company is providing the medication and there’s less of a financial reason to choose one or the other,” Stekler says. “Then people choose either [F/TDF or F/TAF] depending on which long-term side effects that they would prefer to avoid,” since the short-term side effects of both are very similar.
Those with private insurance may be required to try generic F/TDF initially unless, again, there’s a contraindication that enables them to use F/TAF or cabotegravir if they don’t want to use F/TDF. “Unfortunately, insurance tends to drive a lot of this conversation,” says Stekler. Cost-effectiveness analyses of cabotegravir, for example, suggest it’s not nearly as cost-effective as F/TDF, despite a modestly superior efficacy in clinical trials. Cabotegravir often requires prior authorization, including documentation of difficulty adhering to an oral PrEP drug, problems with side effects of the oral drugs, or another reason the patient needs the injection instead, though it may become easier to get cabotegravir in the future, Stekler says.
While patients may not have as much freedom in choosing a particular PrEP medication under their insurance, they do need to know that insurance companies are required under the Affordable Care Act to fully cover PrEP and all associated clinic visits and labs, without any other charges. If a patient’s insurance company is attempting to illegally overcharge them for PrEP or PrEP-related services, they may need help filing a complaint or the paperwork for reimbursement.
Short- and Long-Term Side Effects
Less than 1% of people cannot tolerate PrEP because of adverse effects, based on clinical trials, says Smith. The short-term side effects of F/TDF and F/TAF are very similar: a chance of headaches, fatigue, and gastrointestinal symptoms, such as nausea, vomiting, or diarrhea, in the first couple of weeks. These symptoms usually subside after a month of taking oral PrEP. Some people have found that the nausea and vomiting are milder with F/TAF, Patel says, so someone struggling with F/TDF may want to switch. But again, it often depends on whether their insurance will cover it.
Those taking F/TDF may also experience a rash or weight loss. F/TDF carries a black box warning for those with hepatitis B; they may experience severe flare-ups of hepatitis B symptoms after stopping F/TDF and may need to restart hepatitis therapy.
“It’s really the long-term side effects where they differ,” Stekler says. “[F/TDF] is associated with a small chance of renal dysfunction and a small decrease in bone density over time. [F/TAF] is associated with weight gain and some potential negative changes in lipid profile, compared to [F/TDF].” Some may therefore choose F/TDF to avoid weight gain, while others may choose F/TAF because they’re concerned about long-term bone and kidney side effects, she says.
The change in bone density over time with F/TDF is statistically significant but has limited clinical significance so far because it hasn’t been linked to an increase in fracture risk. At the same time, long-term data for F/TDF use over decades aren’t available yet. “We have a fair number of young folks who are going on [F/TDF], and men lay down bone into their 20s, so if someone is young and potentially on [F/TDF] for decades, it’s something to think about.”
Lifestyle Considerations and Patient Preference
Patients who will be relying on manufacturer payment assistance programs often have the most options, so the clinician can present them with the full menu in starting to discuss which one works best for them, Patel says.
Age is not usually a consideration except that those aged 50 and older taking oral PrEP require a follow-up visit every six months to check their kidney function. There’s a balancing act in considering the comorbidities, risks for which increase with age, such as hypertension, diabetes, high cholesterol, and a history of heart attack, Patel says. If a patient’s comorbidities or risk profile suggest renal disease is a greater risk, that’s a reason to go with F/TAF, but patients who struggle with cholesterol levels may need to go with F/TDF since F/TAF can affect lipid profiles negatively.
The two biggest factors determining whether someone should opt for cabotegravir are whether their insurance or other payer will cover it (unless they’re using the manufacturer payment assistance program) and whether they can come to the clinic every two months for a follow-up appointment and injection, which must be given by a health care provider.
Cabotegravir has only a one-week window around the two-month injections, “so people whose lives [have many] priorities may have a challenge in making those two-month visits,” Stekler says. “I think we’re all really excited about injectables or implants or things that don’t rely on daily adherence, but I think that it’s still uncertain how it’s going to play out in implementation.”
For some people, however, coming to the clinic every two months may be easier than remembering to take a pill every day. Patel notes several reasons that she’s had patients choose the injection over daily oral PrEP.
“No. 1, it’s big and they just don’t like taking it,” Patel says. “Two, there’s stigma associated with having a pillbox and where to keep it. And three, it’s, ‘I can’t take my pill every day.’ Even among people who can take their pill, they say they just don’t like taking it or ‘taking it every day reminds me I have a problem.’” Patel says that people who aren’t able to take the pill every day would rather try the injection. “Coming to the clinic in the era of remote work is easier for some people.”
Avoiding Internal Biases
The decision to prescribe PrEP should not depend on whether a provider believes the patient can take the medication on the schedule recommended. “One of the things we learned in the early days of HIV treatment is that clinicians are very bad at anticipating who can take medication regularly and who can’t, so that should never be the basis for deciding whether or not to offer someone PrEP,” Smith says. “The basis for offering PrEP is that someone is reporting behaviors that may lead to HIV, and you want to help them avoid HIV.”
Clinicians need to be sure they don’t have any unrecognized biases that influence whether they believe a patient can take a daily pill or come into the clinic every two months for an injection. For example, a clinician might initially think someone with housing insecurity is too transient to be able to receive the injection on a regular basis. However, for some with housing insecurity, it may actually be easier to visit a clinic every two months than to keep track of a pill bottle. Some communities may also have systems in place or injection PrEP navigators who can help ensure people get their injection every two months.
Patel says she’s looking forward to seeing whether the injection option affects whether she’s able to focus more on retention in care than adherence for some patients.
“A lot of the clients I see have case managers and are easily retained, but I can’t get adherence at home with a pill, so I’m very optimistic that in some of these patients, can I now get adherence with directly observed therapy if they want the injection?” she says. “I’m not saying it’s perfect—we’re going to have a steep learning curve—but this new modality offers a different way to care for people who are affected by substance use, mental health, and food and housing insecurity.” With the injection, retention and adherence are one and the same, she says.
Providers can check their internal biases by asking themselves if they think this patient is more or less likely to be able to follow a particular regimen and why. Then, they should ask the patient what they feel they can follow best. The CDC PrEP guideline recommends that providers say to patients, “Many people find it difficult to take a medicine every day. Thinking about the last week, on how many days have you not taken your medicine?”
The guideline also offers approaches to effectively support medication adherence, including:
- Educating patients about their medications.
- Helping patients anticipate and manage side effects.
- Asking about adherence successes and issues.
- Helping patients establish dosing routines that work with their schedules.
- Providing reminder systems and tools.
- Addressing financial, substance use disorder, or mental health needs.
- Facilitating social support.
Strategies that can help patients remember to take their PrEP regimen include:
- Setting an alarm on a smartphone, smartwatch, activity tracker like Fitbit, or other device.
- Using a medication reminder app.
- Setting the pill bottle in a location where they’ll see it daily, such as next to their toothbrush, near the coffee maker, near their shoes, or another place they visit or see every day.
- Asking a friend or family member to help remind them.
Understanding the 2-1-1 On-Demand Protocol
On-demand PrEP, also called event-driven or intermittent PrEP, is an option for men who have sex with men with infrequent sexual encounters or those that are planned and predictable, Patel says. On-demand PrEP is not currently approved by the FDA, but two clinical trials—IPERGAYand PREVENIR—have established its effectiveness with F/TDF for both insertive and receptive anal sex.
“We get this all the time, where somebody is in a long-distance, monogamous partnership, and they see their partner every two weeks or every month, and they travel to see them,” Patel says. “It’s a short visit, so they can plan [sex], or they know they’re going to have a period of [sexual] activity that’s infrequent.”
The regimen involves taking two pills in the two to 24 hours before sex, one pill 24 hours after the first dose, and a final pill 48 hours after the first dose. For more information about this protocol, read our on-demand PrEP clinician guide.
