Last week, we described a high-risk young man seeking intermittent pre-exposure prophylaxis (PrEP) for HIV infection and asked whether you would be likely to prescribe PrEP for him. Of the nearly 400 people who responded to our poll, 45% said they would not prescribe PrEP, 35% said they would prescribe intermittent PrEP, and 20% said they would prescribe continuous PrEP. Now, two experts describe what they would do.
THE CASE
A 29-year-old man goes to the emergency department (ED) to request post-exposure prophylaxis (PEP) to prevent HIV infection. He has just returned from a week-long vacation, during which he had unprotected oral and receptive anal intercourse with several men whose HIV status he does not know. His last HIV test was 6 months prior to this ED visit, and the result was negative. He reports no medical problems and is not taking any medications. He receives a 28-day course of tenofovir/FTC + lopinavir/ritonavir PEP.
Four days later, the patient has a follow-up visit with his primary care provider (PCP), who is aware that he has received at least three similar courses of PEP during the previous 4 years. His HIV antibody test has again returned negative. He says he is aware of when he is going to put himself at high risk for HIV infection (usually during vacations and particular weekends) and would like a supply of tenofovir/FTC to take during these periods; however, he does not want to take the drugs continuously.
If you were the PCP, what additional history would you obtain? Would you try to change the patient's high-risk behavior? If so, what specifically would you say to him? Would you recommend tenofovir/FTC pre-exposure prophylaxis (PrEP) for him? If so, would it be continuous or intermittent? How frequently would you monitor for HIV, other sexually transmitted infections (STIs), and tenofovir/FTC toxicity? If you would not prescribe PrEP, what is your reasoning?
RESPONSE 1
— Anthony Mills, MD
I would begin with a frank, nonjudgmental discussion with this patient about his exposure history, including use of recreational drugs and alcohol, possible sources of infection, and the likelihood that any of his partners could be contacted for further inquiry. I would certainly have a heart-to-heart conversation with him about the risks that he is taking and would work with him to put together a risk-reduction plan, which may include referral to a case manager or psychotherapist to focus attention on why he takes these risks. I would also determine his hepatitis serology status and screen him for various STIs, including syphilis and hepatitis B and C.
Although the iPrEx study supports the use of PrEP in high-risk men who have sex with men (MSM;
N Engl J Med 2010; 363:2587), I would only consider prescribing it to this particular patient after extensive testing and discussion. Establishing his HIV status for certain, although difficult, is a key priority. Men in iPrEx who were antibody-negative but HIV-infected at study entry were at risk for developing drug resistance. To ensure that this patient is truly HIV-negative, I would recommend that he undergo both HIV antibody testing and HIV viral-load testing 4 to 6 weeks after he has completed his course of PEP.
In discussing PrEP with this patient, I would emphasize that it should never be the first line of defense against HIV infection. PrEP has been shown to be beneficial only in the context of condom usage and regular testing for HIV and other STIs. Furthermore, oral PrEP must be taken every day. Although the use of tenofovir gel before and after sex reduced the risk for HIV infection among women in CAPRISA 004 (
Science 2010; 329:5996), intermittent use of oral tenofovir/FTC was not effective among men in iPrEx and cannot be recommended without further study.
If this patient proves to be HIV-negative, is willing to work together to reduce his HIV risk, is willing to take PrEP every day, and is committed to close regular follow-up, then and only then would I consider PrEP for him. I would prescribe no more than a 90-day supply of tenofovir/FTC, and I would recommend follow-up visits at least every 3 months. At these visits, I would check his HIV antibody status (and other safety labs as needed), evaluate his adherence, assess his risk behaviors, test and treat for other STIs, and provide risk-reduction counseling, condoms, and his next 90-day PrEP prescription.
RESPONSE 2
— Demetre C. Daskalakis, MD
I would obtain a social and mental health history to better understand what might be influencing this patient's sexual risk-taking. I would explore his use of alcohol and recreational drugs, such as methamphetamine, and assess the need for a referral to mental health care. I would also ask him why he engages in unprotected sex and confirm that he understands the medical implications of HIV infection. Finally, I would also search for symptoms of acute HIV infection and other STIs.
Changing his sexual behavior would be difficult. Although PCPs have a role in risk reduction, this patient requires more-intensive prevention counseling than is offered in a standard medical practice.
I would not prescribe PrEP to this patient at this time. He has expressed a clear desire for intermittent antiretroviral use, but no data are available on the safety and efficacy of this intervention. The iPrEx study only supports daily PrEP with a high level of adherence (
N Engl J Med 2010; 363:2587), and I am concerned that we do not know enough about the correct timing of intermittent PrEP to ensure preventive efficacy. A broader issue is that the healthcare system currently lacks the infrastructure to support PrEP care in the manner recommended by the CDC (
MMWR Morb Mortal Wkly Rep 2011; 60:65). For example, although the CDC recommends PrEP use in high-risk MSM, there is little if any third-party payer coverage of antiretrovirals for preventive indications.
For MSM who are willing to take continuous PrEP and are able to pay for their own drugs (and, potentially, for HIV and STI testing as well, if the frequency required is not covered), I would consider prescribing daily tenofovir/FTC. I would follow the CDC PrEP guidance, with some variation based on my HIV primary care experience. For example, the CDC recommends testing for HIV every 2 to 3 months and for other STIs every 6 months; however, I would test for both every 2 to 3 months, regardless of symptoms. Similarly, the CDC recommends evaluating renal function at baseline, at 3 months, and then annually. However, I would check renal function more frequently and also assess baseline liver function, evaluate blood counts, and perform a urinalysis to monitor drug toxicity.
FOLLOW-UP
As anyone practicing HIV medicine or engaged in HIV research can tell you, the publication of the iPrEx study raised as many questions as it answered. Nonetheless, the application of the study results to clinical practice has already become a reality.
The case presented here — adapted from one seen in our clinic only a month after the iPrEx results were released — raised considerable controversy among our providers, most of whom thought the patient should not be prescribed PrEP because he was not committed to continuous therapy. This view was shared by our two expert respondents and by most of the readers who weighed in with
comments or votes online. Of considerable interest is that the second most common response was to prescribe intermittent PrEP, even though this strategy has not yet been shown in clinical studies to be effective.
Despite this majority view not to prescribe PrEP, one respondent raised an interesting point under the title "Double Standard?" She writes:
"How is this different than prescribing a PPI for heartburn when a patient refuses to give up coffee or a statin for hypercholesterolemia when a patient will not make dietary modifications? Our business is to prescribe medicines to mitigate risk when people do not (for whatever reason) make healthy lifestyle choices."
Indeed, this legitimate perspective in favor of PrEP highlights just how challenging the issue of PrEP will be in clinical practice.
Dr. Mills is in private practice in Beverly Hills and is an Assistant Professor of Clinical Medicine at the University of California, Los Angeles. He reports no conflicts of interest.
Dr. Daskalakis is an Assistant Professor of Medicine and Director of the Men's Sexual Health Project at New York University Medical Center. He reports no conflicts of interest.
2 weeks of follow-up (mean age, 32.1; median follow-up, 27.5 months). The incidence of new genital HPV infection was 38.4/1000 person-months and did not vary with age. Median time to clearance was 7.2 months for oncogenic HPV types and 7.6 months for nononcogenic types. This interval was significantly longer in 18- to 30-year-olds than in older men. In multivariate analysis, oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners or recent male anal-sex partners.
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2 nucleoside reverse transcriptase inhibitors. Forty-six percent of the patients had never received a protease inhibitor (PI) before, and 84% of the patients had no major PI mutations.