Will Final Guidelines on PrEP Stimulate More Use in Clinical Practice?

When the US Food and Drug Administration (FDA) approved tenofovir disoproxil fumarate plus emtricitabine (Truvada) as pre-exposure prophylaxis (PrEP) for HIV prevention in July 2012, it unleashed a torrent of reaction from clinicians and advocates in the HIV community, with some calling it “the new condom” and others pillorying as unsafe and potentially dangerous.¹

In mid-May, the Centers for Disease Control and Prevention released final guidelines on the use of PrEP in clinical practice.² This time, the reaction was largely positive, with 134 leading HIV/AIDS and health organizations hailing the guidelines as “a science-driven, public health approach to what remains a major health crisis in the United States.”³

The CDC released interim guidance on the use of PrEP in gay men in early 2011, after results from  the men who have sex with men (MSM) PrEP study were released, then interim guidance for heterosexuals in 2012, when the heterosexual study was published, and then additional interim guidance in 2013 for injection drug users. 

What is different about the new  guidelines, said Jared Baeten MD, is that the earlier guidance documents were brief and the new guidelines are comprehensive. Dr. Baeten, who is professor of Global Health in the University of Washington’s School of Public Health in Seattle, was one of the lead researchers in the seminal trials that led to the FDA approval of PrEP.

The new guidelines also include recommendations for its use in women, including during conception, pregnancy, and breastfeeding.² This is particularly relevant as officials estimate there are 140,000 heterosexual couples in the US in which one partner is infected and the other is not, about half of whom would like to conceive.⁴

“It’s fantastic to have guidelines, and fantastic that they are so comprehensive and smartly designed,” said Dr. Baeten. “I’m seeing very positive reaction across the spectrum of public health folks, practitioners, advocates, and community members.”

Interest in PrEP is particularly high in the United States, where younger generations of high-risk individuals who view AIDS as a treatable, chronic disease are eschewing condom use. In fact, a CDC meta-analysis of studies on condom use in gay men in the US found that just one in six men report 100% condom use.⁵ Studies find, however, that taken as directed PrEP is just as effective at preventing HIV transmission as condoms. ^6,7

“It is concerning that few people are using condoms,” said Dr. Baeten. “It opens up the possibility that the country would not see fewer infections but could see more in the absence of PrEP, and that would be devastating.” It’s also a reminder, he said, that PrEP offers the opportunity to prevent HIV in the context of these risks.

Uptake in Clinical Practice Slow

Nonetheless, uptake of PrEP to date has been slow in many communities, something that doesn’t surprise Dr. Baeten. “PrEP is something new, and fitting something new into any public health [system] and prescribing structure needs time and energy and thought,” he said. Other clinicians echo his thoughts.  One doctor from Vanderbilt University told The New York Times in mid-May that “the average doctor is still only dimly aware of this.”

One problem is that the clinicians most familiar with PrEP-those who care for people with HIV/AIDS-are not the ones who prescribe PrEP. “The best opportunity for PrEP to have a real impact for individual patients and for public health is if it finds its way into primary care, with ‘primary care’ broadly defined,” Dr. Baeten said. That means sexually transmitted disease (STD) and other community clinics, as well as private practices.

Yet an Internet-based survey of more than 9,000 MSMs found just 1% of this high-risk population were using PrEP, even through a bit more than half reported anal sex without condoms at least once in the past three months. A major reason for the low numbers? Only half felt they could discuss sex with their primary care physician. ⁸

A qualitative study published in 2012 that involved in-depth interviews with 22 healthcare providers in California about integrating PrEP into clinical practice identified several potential barriers:⁹

•  Little consensus on PrEP target populations
•  Current models of care and skill sets not always well suited for prescribing PrEP
•  Capacity building required, including training, referrals, and reimbursement
•  Concerns about monitoring adherence, side effects, resistance, and risk compensation
•  Skepticism about the efficacy of PrEP in preventing transmission

“The biggest barriers I’ve seen to PrEP are knowledge barriers on the part of clinicians and patients,” Dr. Baeten said. “The people who can take it aren’t aware it is out there or how to get it or ask for it; and the clinicians have been uncertain about how they can provide it and how it fits into HIV care and into primary care.”

He is hearing more interest from potential patients, however, and the media attention to the CDC guidelines will likely increase that. “My HIV-infected patients are also interested (for their partners) because they are interested in preventing transmission.”

Early Experience with PrEP

A study of early experiences with PrEP in San Francisco, which has one of the country’s highest per capita rates of HIV-infected individuals, holds several interesting lessons for public health officials and clinicians.¹⁰ The study reported on three demonstration projects in the first year after the FDA approval: a National Institutes of Health-funded project in an STD clinic, and delivery programs in a managed care organization and an HIV-specific reproductive health clinic. Key findings included:

•  Patients feel significant stigmatization around the use of PrEP, reporting that their peers believe that taking PrEP will encourage risky behavior and divert resources from HIV-positive people, while medical providers appear “judgmental” about their decision to use it and often don’t want to prescribe it. This stigma poses a major barrier to uptake, the authors concluded.
•   A quarter of patients in the managed care population prescribed PrEP discontinued it. The main reasons were decreased risk perception and side effects.¹⁰
•   Consumer education and knowledge is critical to increase awareness.
•   Patients need more information about the risks of HIV infection compared to the potential side effects of PrEP.
•   Clinics need appropriate capacity in terms of staff, time, space, and expertise to manage the demand for PrEP in the short- and long-term.
•   Insurance coverage is an important consideration in uptake.

Considering the Cost

There’s no doubt that the widespread use of PrEP will be expensive. Currently, the drug costs between $700 to $900 a month in the United States and cost- effectiveness analyses are mixed.¹¹

One analysis found that initiating PrEP in 20% of men who have sex with men  would reduce new HIV infections by about 13% over 20 years at a cost of $172,091 per quality-adjusted life year (QALY) gained, translating to a cost of $2 million per infection prevented.¹²  Economists generally consider $50,000 per QALY the threshold for cost effectiveness.  Once the drug is available in generic form, however, the cost effectiveness should significantly improve.¹¹

However, the researchers found, using the regimen only in high-risk MSMs makes it more cost effective,  resulting in a cost of $50,000 per QALY gained. Healthcare-related costs would be an addition $75 billion, or about $600,000 per HIV infection prevented.¹²

Most insurance companies and state Medicaid systems cover the drug, although many require preauthorization. That may be changing, however. MediCal in California, for instance, eliminated a prior authorization requirement in May ahead of the CDC announcement, striking down one prescribing barrier.¹³

Despite the challenges ahead with PrEP implementation, Dr. Baeten is optimistic.

“To move so rapidly from the trials to FDA approval to national guidelines on integrating the use of PrEP into community practice is an amazing evolution,” he said.

References:

1.    Glazek C. Why is No One on the First Treatment to Prevent HIV? The New Yorker. October 1, 2013.
2.    Centers for Disease Control and Prevention. Pre-exposure prophylaxis for the Prevention of HIV Infection in the United States - 2014 Clinical Practice Guidelines. (2014)
3.    Leading HIV/AIDS groups endorse CDC HIV PrEP Guidelines; Reiterate that PrEP is a powerful, additional tool in the AIDS response. myprepexperience.blogspot.com (blog sponsored by AIDS Chicago). May 19, 2014.
4.    Aaron E, Cohan D. Preexposure prophylaxis for the prevention of HIV transmission to women. AIDS. (2013) 27:F1-5.
5.    Smith D, et al. Condom efficacy by consistency of use among MSM: US. Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013; Atlanta.
6.    Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. (2012) 367:399-410.
7.    Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.N Engl J Med. (2012) 367:423-434.
8.    Mayer KH, et al.

Top Antivir Med. (2014) 22(e-1):496.
9.    Arnold EA, Hazelton P, Lane T, et al. A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection.PLoS One. (2012) 7:e40603.
10.    Liu A, Cohen S, Follansbee S, et al. Early experiences implementing pre-exposure prophylaxis (PrEP) for HIV prevention in San Francisco. PLoS Med. (2014) 11:e1001613.
11.    Li J, Dufrene SL, Okulicz JF. Systemic preexposure prophylaxis for HIV: translating clinical data to clinical practice.Ann Pharmacother. (2014) 48:507-518.
12.    Juusola JL, Brandeau ML, Owens DK, et al. The cost-effectiveness of preexposure prophylaxis for HIV prevention in the United States in men who have sex with men.Ann Intern Med. (2012) 156(8):541-550.
13.    McCrory W. ASOs Applaud Use of Truvada. EDGE Washington.  May 7, 2014. Accessed May 22, 2014.