Two recently released clinical practice guidelines by the Centers for Disease Control and Prevention and the World Health Organization now encourage preexposure prophylaxis for patients at risk for HIV infection. Despite the reach and influence of these organizations, however, the potential to prevent further infections may depend on how clinicians take up the cause in their primary care practices.
The Centers for Disease Control and Prevention's clinical practice guideline on preexposure prophylaxis (PrEP) for HIV, released in May, highlights the effectiveness of a combination drug regimen for preventing HIV infection among several at-risk populations. The World Health Organization's guidelines on HIV prevention, diagnosis, and treatment, released in July, strongly recommend for the first time that men who have sex with men consider taking PrEP along with using condoms. To find out which of their patients should be taking PrEP, primary care physicians along with other clinicians will need to be prepared to have personal and uncomfortable discussions with their patients about sexual behaviors and drug use.
“As part of our understanding of who our patients are and what kinds of risks they may be exposed to, we should all be taking a thoughtful and careful sexual history, which may be considered intrusive, and we should be trying to understand our patients' substance use,” said Molly Cooke, MD, MACP, professor of medicine and director of education for global health sciences at the University of California, San Francisco.
“These are famously difficult conversations even for experienced clinicians, and for many of us they remain difficult,” said Dr. Cooke, immediate past president of ACP. “But we should definitely have these discussions that should allow us—unless the patient is intentionally concealing information for one reason or another—to identify people who may be at risk.”
Populations at risk
The CDC guideline recommends the antiretroviral drug combination of tenofovir disoproxil fumarate and emtricitabine for several groups of adult patients who are considered at substantial risk for HIV acquisition:
- men who have sex with men if their partner is HIV positive, if they have multiple partners, and if they have had condomless sex at any time in the previous 6 months;
- heterosexually active men and women if their partner is HIV positive, if they have multiple partners of either sex, if they have had a recent bacterial sexually transmitted infection, and if they have had condomless sex with HIV-positive partners; and
- injection drug users who use needles or other preparation equipment already used by someone else, have been in a methadone or other medication-based drug treatment program in the previous 6 months and are currently injecting, or have an HIV-positive injecting partner.
PrEP should be discussed with heterosexually active men and women whose partners are known to have HIV infection as one of several options to protect the uninfected partner during conception and pregnancy, the guideline stated.
Like the CDC guideline, the WHO advises that PrEP be used by men who have sex with men as part of an additional HIV prevention package that includes correct and consistent use of condoms with condom-compatible lubricants. Daily PrEP should also be considered for the uninfected partner within a serodiscordant couple. The WHO recommends that voluntary HIV testing and counseling be offered for patients at risk, and that clinicians initiate this testing and counseling.
The presence of acute or chronic HIV infection must be excluded by symptom history and HIV testing immediately before PrEP is prescribed, according to the CDC. No patient who tests positive for HIV should take the drugs. Any patient prescribed PrEP must be retested for HIV infection every 3 months before the prescription is refilled for another 3 months. Anyone with an incident infection should not have the prescription refilled. The drugs are also contraindicated if a patient's creatinine clearance is less than 60 mL/min, the CDC cautioned.
Patients should be counseled that PrEP must be taken daily and that it will not be effective if used intermittently. Unlike drugs for hypertension or cholesterol, which can be used again if the patient is nonadherent, irregular use of PrEP introduces more risk. And, if patients acquire HIV while on PrEP, there is the possibility that they may develop resistance to the drugs in the regimen. These agents are also used in HIV treatment, so resistance may limit their future therapies, according to Dr. Cooke.
People at risk for HIV must continue to use condoms even when they are taking PrEP every day, the experts stressed. “It should never be an issue that if you use PrEP you don't have to use a condom,” said Stacey Rizza, MD, chair of the HIV Clinic at Mayo Clinic in Rochester, Minn., and associate professor of medicine. “Injection drug users still need to use clean needles, and if people have multiple partners, then they need to find out if their partners are infected. All the other education and other safe sex practices that have been recommended before are still important.”
Demetre Daskalakis, MD, MPH, medical director of ambulatory HIV services at Mt. Sinai Hospital and associate professor at Icahn School of Medicine in New York, said that PrEP is ideally a supplement to maximize adherence to condoms. PrEP can be a backup “if something goes wrong or if you are in a situation where condoms can't be used,” he said. Plus, condoms can help prevent other sexually transmitted diseases. “The messaging should be that PrEP gives you another tool to prevent HIV, but all those tools should be used in combination,” he said.
Have the conversation
Primary care doctors are well positioned to discuss HIV risk with their patients and to discuss use of a medication regimen that could protect them from that risk, said Dr. Daskalakis, who was a member of the FDA advisory committee that recommended approval of PrEP. “This is something that could have 90%-plus efficacy in preventing HIV, but if you don't know whether your patient needs it and they don't acknowledge that they need it, then it will not make any impact,” he said.
Many people who are PrEP candidates do not know their risk of HIV infection. In a study published in the June 2014 LGBT Health, Dr. Daskalakis and colleagues found that 22% of men having sex with men who were included in the study and met eligibility criteria for HIV prophylaxis did not think they were at sufficient risk to warrant use of the drugs.
Assessing a patient's risk—and educating the patient about that risk—begins with asking questions, such as whether the patient has made a change in sexual partners or whether the patient has made a change in a previous monogamous relationship. Answers to other questions help the physician assess the patient's risk and start the conversation about safe sex practices and the possible need to consider PrEP:
- Have you had more than 1 sexual partner in the last 6 months?
- If you are a man who has sex with another man, have you had sex without a condom even once during the past 6 months?
- Do you know whether your partner (or partners) has been tested for HIV?
- Has your sexual partner changed since the last time you were in my office?
- Do you use any IV drug?
“I think it's fair to ask every primary care doctor to regularly ask those questions,” Dr. Cooke said. “If the patient says they are still in a monogamous relationship, then move on to something else. But most primary care doctors don't ask.”
Dr. Daskalakis recommends that the conversation be extended if the patient is at risk, saying to the patient: “If you use condoms 100% of the time, you probably don't need to take a pill a day. In that case, if there is a condom mistake or break, you should know that there is something called PEP (post-exposure prophylaxis) that you need to start within 72 hours and continue for 28 days. If you use condoms inconsistently, and are in an HIV epidemiological risk environment, then PrEP may be right for you.”
Managing and following patients who are at risk for HIV infection and are prescribed PrEP can be challenging for primary care physicians. In addition to patient education about the need for daily adherence and continued condom use, education about safe sex in general and safe needle use is also needed. Because the PrEP drug combination is new, some doctors may have no experience with the drugs in either of the classes involved and may be reluctant to use them, Dr. Cooke said.
However, primary care physicians who refer their at-risk patients to HIV specialists for PrEP management should gradually become more comfortable as they observe how doctors with more experience handle the medication and patient follow-up, Dr. Cooke noted. They may eventually start managing their own patients.
“This really isn't all that difficult and complex. These patients don't have HIV,” she said. “We're talking about 1 pill a day and a little bit of surveillance from the lab point of view and referral to community resources that the patient may need.”
Dr. Rizza agreed that even if primary care physicians are reluctant to manage patients at risk for HIV infection, they should be willing to screen, to be aware of their patients' risks and the availability of PrEP, and to “have an HIV doc in their pocket that they refer the patient to.”
Although PrEP does not treat acute or chronic HIV infection, there is hope that its use—along with condoms—will ultimately diminish the HIV epidemic as more cases are prevented, according to Dr. Daskalakis. Some studies have shown that over half of new HIV infections are transmitted by acutely infected people who may not be aware of their status, and PrEP helps prevent acute infection, he said.
“For me, there is this secret public health piece that if you have less seroconversion, you are going to have less forward transmission, and that may impact the dynamics of the epidemic. We look at tobacco screening as a quality indicator. It is almost time to start thinking about sex risk-taking as another,” he said. “A primary care doctor would not dream of not asking about tobacco. Talking about sexual risk-taking should be a casual part of our interaction with patients, something that we acknowledge and deal with.”