Access Restrictions to HIV Pre-Exposure Prophylaxis (PrEP) May Lead to Unintended Consequences

Despite federal, state, and societal goals to curb the human immunodeficiency virus (HIV) epidemic, HIV continues to be a significant health burden in the United States. In February 2019, the US Department of Health and Human Services committed to end the HIV epidemic by reducing annual new infections by 75% within 5 years and 90% within 10 years.¹ PrEP for HIV prevention plays an important role in meeting those goals.¹

The objective of this commentary is to address current patient awareness and usage of PrEP for HIV, the cost-effectiveness of medication options, barriers to usage, and the impact of prescription nonadherence and patient walkaway rates.

At the end of 2018, it was estimated that 1.2 million people in the US were living with HIV or acquired immunodeficiency syndrome (AIDS), which is caused by HIV.² Nearly 40,000 Americans are newly diagnosed every year, and 700,000 Americans have died due to HIV since 1981.¹ Even more concerning is the fact that Black and Latinx Americans are disproportionately affected. In 2018, Black and Latinx people accounted for 69% of all new HIV diagnoses, yet they make up only 31% of the US population.³

As the HIV/AIDS epidemic persists, the disease presents a considerable cost burden. Based on data from the years 2002-2011, the incremental annual cost of treating patients with HIV/AIDS was estimated to be approximately $10.7 billion higher in the US than the cost for people without HIV/AIDS.⁴ Today, that number has ballooned to an estimated $20 billion per year.⁵

Controlling the HIV epidemic is a multi-pronged effort, requiring wide-spread education for insurers/payers, providers, and patients on prevention and treatment; antiretroviral therapy for people with HIV; pre-exposure prophylaxis (PrEP) for at-risk people; behavioral changes; and harm reduction interventions.^6-9

Oral PrEP is the use of oral antiretroviral (ARV) drugs before HIV exposure, taken by people who are at risk for HIV.⁶ The use of antiretroviral therapy (ART) as PrEP to prevent the acquisition of HIV was first approved by the FDA in July 2012. When used as prescribed, PrEP provides high levels of protection, blocking the acquisition  of HIV.^6,7 In addition, when used broadly by people within locally defined at-risk populations, PrEP has a significant influence on reducing the incidence of HIV transmission events at the population level.⁷

The use of PrEP as a health care strategy for preventing HIV is recommended in guidelines from the Centers for Disease Control and Prevention (CDC),¹⁰ the International Antiviral Society–USA (IAS-USA),⁷ and the World Health Organization (WHO).⁶ The combination of tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) is the WHO’s recommended oral PrEP regimen for all at-risk populations.⁶ 

In 2012, TDF/FTC, the first antiretroviral drug, was approved by the FDA for PrEP. A second antiretroviral medication, tenofovir alafenamide plus emtricitabine (TAF/FTC), was approved for PrEP in 2019.⁸

Both products show similar efficacy rates (>99% effective when used and adhered to as prescribed).⁷ The CDC currently recommends TDF/FTC for all men, women, and transgender people at risk of HIV infection through sex or injected drug use^10,11 and TAF/FTC for men and transgender women who have sex with men.¹¹ Both drugs have similar safety profiles and are considered safe and well-tolerated by most patients.⁸ TAF/FTC has been shown to be safer for people with bone or kidney issues.¹²

Although awareness and use of PrEP appears to be growing, its use is still lower than desired, based upon current treatment guidelines. In fact, the CDC estimates only 1 out of 5 people who could benefit from PrEP are actually receiving it.¹³ Siegler et al estimated even lower, at less than 10%.¹⁴

There appears to be a correlation between increased awareness of PrEP for HIV and increased willingness to use PrEP. In 2016, Huang et al estimated 1.1 million people in the US had an indication for PrEP, yet only about 7% of the population was prescribed PrEP. Although the numbers of prescriptions for at-risk people was still extremely low, the study authors noted a significant increase (470%) in the use of PrEP by users age 16 years and older from 2014 to 2016.¹⁵ Of these, the majority (68.7%) were white. Only 4.7% were women, 11.2% were Black, and 13.1% were Hispanic,¹⁵ pointing to a disparity in usage.

PrEP awareness has increased since its introduction. Finlayson, et al, showed that among men who have sex with men (MSM) living in 20 urban areas in the US, awareness increased from 60% to 90% from 2014 to 2017. At the same time, PrEP use increased from 6% to 35%, although lower among Black and Hispanic MSM (Figure 1).¹⁶ 

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Siegler et al determined that nearly 50% of new US HIV diagnoses occurred in the South, but that region showed lower PrEP usage rates than in the Northeast and West, and similar rates to the Midwest. The authors posited that the lower PrEP usage and higher HIV infection rate were likely due to larger percentages of the population in some states in the South being residents who were living in poverty, were uninsured, and were African American. They also indicated usage was higher in states with expanded Medicaid under the Affordable Care Act and where Medicaid covered routine HIV screening costs. Usage of PrEP was also much higher for men than for women.¹⁴

There appears to be a significant opportunity for increasing education around PrEP and raising awareness in at-risk communities about PrEP’s benefits in preventing the acquisition of HIV. This opportunity for increasing awareness and subsequent use is particularly critical in underserved populations, such as women, Black, and Latinx people.

The WHO’s guidelines on HIV prevention indicate that offering PrEP to patients is expected to be cost-effective in many high-incidence situations, especially in areas where the incidence of HIV is more than 3 out of 100 people per year. Prioritizing people at risk increases the impact of PrEP on reducing the number of infections, which can be cost-effective depending upon the cost of the delivery systems and the cost of HIV treatment if PrEP is not used.⁶

The cost of PrEP is approximately $21,600 per patient per year.¹⁷ In addition, Smith et al estimated that the costs of lab tests for a year are between $502 to $1721 and clinician visits for a year are $422, for a total between $924 to $2143.¹⁸ Therefore, the total cost of PrEP therapy is less than $23,743 per year. In comparison, McCann et al estimated the average annual cost of initial ART for people with HIV at more than $36,000 per patient,¹⁹ while Enns et al estimated the annual average costs of HIV treatment ranging from $35,300 in the Northeast to $41,528 in the South.²⁰ When comparing these estimates of annual HIV treatment costs to PrEP costs, the average annual HIV treatment costs range from $11,557 to $17,785 higher than the average annual cost of PrEP therapy.

PrEP appears to be cost-effective in the US, with acceptable willingness-to-pay thresholds for patients who are at high risk for HIV infection.²¹ Chen and Dowdy developed a decision analytic model of PrEP for MSM, which serves both as a population cost-effectiveness calculator and an individual risk calculator. Their model showed that the use of PrEP was cost-effective for high-risk individuals in populations with a 35% HIV prevalence ($27,000/Quality-adjusted life year [QALY]) and in the base case ($160,000/QALY).²¹ Cost-effectiveness is the cost of an intervention per every QALY gained, with therapies traditionally considered cost-effective when below $100,000 per QALY but with more recent estimates of cost-effectiveness ranging up to around $300,000/QALY.²² The authors found that “effectiveness and cost-effectiveness of oral PrEP is highly dependent on condom use, HIV prevalence, PrEP adherence, and the degree of behavioral disinhibition…”²¹

Bernard et al developed a model to evaluate the cost-effectiveness and optimal delivery conditions of PrEP for people who inject drugs. They determined that PrEP when given alone or combined with frequent screening of people at risk for HIV and enhanced ART provision for those infected with HIV would reduce HIV prevalence over 20 years in the study’s population. The cost/QALY was estimated at $253,000 for PrEP combined with screening and ART for people with HIV.²³

When PrEP is used as prescribed (daily) or consistently (4+ times a week), the protection afforded by PrEP for HIV is extremely high (>99%).^7,24 PrEP effectiveness does not differ based on age, sex, type of ARV, or mode of exposure (rectal, penile, or vaginal). However, there is a strong correlation between adherence and the level of protection.^6,24 The less a person adheres to the PrEP regimen, the lower the level of protection they receive. PrEP protection is highest among high-adherence people (>70% drug detection), and relatively high with moderate adherence (41-70% drug detection). Low adherence (<40% drug detection) shows no effect in reducing HIV infections.⁶ 

The health impact of nonadherence to PrEP or disruptions in the continuity of care with PrEP by at-risk people is high, causing an increase in subsequent HIV infections. The costs to treat this lifelong infection are significant. The CDC estimates that avoiding one new HIV infection can save an average of $850,557 in lifetime health care costs.²⁵

Regrettably, at-risk people experience considerable barriers to accessing and adhering to PrEP. These barriers disrupt continuity of care, contribute to adherence problems, and increase walkaway rates for people who are indicated for PrEP. The walkaway rate is defined as the total of claims rejected by the insurer/payer for prescribed product and not filled with an alternative PrEP product, plus prescriptions abandoned at the pharmacy. 

Cost is one of the first barriers to consider for people wishing to use PrEP for HIV.^7,26 Previously, most insurers/payers covered PrEP but may have required patient cost-sharing via copayments or deductibles. As of January 1, 2021, patient cost-sharing should be eliminated for most commercial plans and plans covering Medicaid expansion populations, due to the A recommendation from the US Preventive Services Task Force.^27,28 The Affordable Care Act requires that preventive services that receive an A or B rating from the US Preventive Services Task Force must be covered by most private health plans without making members share the cost through copayments or deductibles.^28,29 When copays and deductibles are eliminated, the only financial barriers that remain for insured patients are lab and clinical services associated with these medications.^27,28 Without federal guidance to clarify that all PrEP-related ancillary tests and services must be covered with no cost-sharing, it is unclear if private insurers/payers will cover these costs.²⁸ California and New York require health plans to cover these costs without cost-sharing for patients.^27,30 However, information on other states is limited. For uninsured patients, costs for drugs and services remain a barrier.²⁸

Coverage restrictions, such as prior authorizations, present another barrier to PrEP, with their effect becoming more apparent with recent changes to coverage policies implemented by some health plans. These changes appear to delay or discourage PrEP prescription fills, inadvertently increasing walkaway rates.

A recent analysis of Symphony Health Solutions (SHA) prescription data (all claims submitted before adjudication, i.e., both paid and rejected claims) examined the impact of PrEP coverage restrictions implemented by two large national health care plans (prior authorization, with documented medical exceptions in most cases) for their commercial population on walkaway rates.³¹ The coverage restriction from these two national plans appears to have been put in place in anticipation of the market introduction of a generic version of TDF/FTC, with the goal of steering patients to the generic.

In the months that led up to the restriction (June, July, and August 2020), the walkaway rate for TAF/FTC (in Plan A nationally) was steady at approximately 25% for PrEP-naïve patients. In September 2020, when Plan A no longer covered TAF/FTC, the plan’s walkaway rate rose to 35% for naïve patients (Figure 2). Plan B’s walkaway rate increases were similar after implementing coverage restrictions in May 2020 for TAF/FTC, with walkaway rates rising from 19% in March and 32% in April to 46% for TAF/FTC for naïve patients in May (Figure 2).³¹

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In comparison, the national walkaway rate for TAF/FTC averaged 19% for PrEP-naïve patients from January to November 2020 (all plans excluding Plan A and Plan B). In California, where state law prohibited health plans from requiring prior authorization or step therapy for PrEP products,³² the walkaway rate for September was 30% for Plan A and 25% for plan B (Figure 3). Walkaway rates were dramatically lower in California than nationally for both plans in October and November (Figure 3).³¹ 

Trying to move patients to the generic product had the unintended consequence of causing nearly one-third to one-half of all new patients prescribed TAF/FTC not receiving any PrEP medication.

When surveyed, 90% of physicians say they believe that prior authorizations have a negative impact on patient clinical outcomes, and 74% say a prior authorization requirement can at least sometimes lead to treatment abandonment—or walkaways.³³ Delays in the introduction of PrEP for HIV caused by prior authorization requirements increase the likelihood that the person will be exposed to HIV before obtaining the drug.

These insurance restrictions also present additional problems in underserved communities. Just as efforts are being made to understand and address socioeconomic and racial disparities to increase use of PrEP in at-risk populations that have difficulty in accessing medical care, coverage restrictions present additional barriers to PrEP for those very populations.

In addition to costs and coverage restrictions, other barriers to PrEP for HIV include:²⁶

• Low awareness of PrEP by at-risk individuals;²⁶
• Inaccurate perception of HIV risk by at-risk individuals;^26,28
• Potential stigma of being identified as having HIV or of being shamed;^6,26
• Distrust of health care providers, including fears of homophobia or racism;²⁶
• Lack of access to providers and medical care, including distance, transportation, homelessness, and lack of HIV- or LGBTQ-experienced providers;^26,28
• Low awareness and reluctance of providers to offer PrEP;²⁶
• Limited government support for PrEP assistance programs such as AIDS Drug Assistance Programs (ADAP), which help pay for drugs for people living with HIV; and 
• Such assistance programs should be streamlined; burdensome applications and 6-month renewal processes pose another barrier.^34,35

Despite the clear advantages to PrEP for HIV, major barriers are blocking its usage by at-risk individuals. Solutions to these problems will require the combined efforts of insurers/payers, manufacturers, pharmacists, and providers. Some solutions may be more immediate; others may be more complex.

A clear first step for insurers/payers would be to evaluate PrEP utilization trends within their own population data. Identifying walkaway and adherence rates within their own target populations will show insurers/payers whether their current coverage policies are actively working towards the Ending the HIV Epidemic initiative’s goals, and could highlight areas for immediate action in reviewing or revising coverage policies to align with HIV prevention guidelines. Such a review could also reveal unexpected or unconscious biases within the organization, where benefit designs to support the at-risk population may have been de-prioritized. Insurers/payers could then create action plans for both providers and patients to encourage usage and adherence to PrEP for HIV.

Insurers/payers can also partner with manufacturers to reduce barriers and increase access to those who need prevention the most. This may include outcomes-based incentives for reimbursement and patient assistance programs to provide initial access with a long-term plan for sustainability beyond one year. Addressing these issues will increase the likelihood of patients going to the pharmacy to pick up their prescriptions once they know they can afford it.

Removing cost barriers to PrEP will require coordinated efforts between federal and state agencies, manufacturers, insurers/payers, and health care providers. Expanding manufacturer-sponsored³⁶ and government-sponsored cost-sharing assistance programs for PrEP (such as Ready, Set, PrEP from the US Department of Health and Human Services^37,38) would help more at-risk people afford PrEP drug. Additional support to address other barriers, such as transportation to clinics and pharmacies, and to support community health care centers in their efforts to provide PrEP care^39,40 would also improve access.

Better education of payers/insurers, pharmacists, and health care providers across the spectrum from general practitioners to specialists is required to raise their awareness of the benefits of PrEP for HIV. This improved awareness is likely to lead to a reduced number of new HIV infections.⁶ Pharmacy management programs, digital therapy, supplemental adherence programs, and other tools could be used to increase adherence above 40%, which has been shown to be the minimal level of effectiveness. Payers/insurers, providers, and pharmacists should also be educated on the fears expressed in the community of potential bias or stigmas.

Additionally, there is a continuing need for better education for at-risk individuals themselves, to raise their awareness of the benefits of PrEP.

To help curb the HIV epidemic, it is essential to raise awareness among insurers/payers, providers, pharmacists, and patients on three crucial points: the guidelines for HIV prevention that strongly recommend PrEP, the dangers of walkaways and nonadherence, and the impacts that insurance barriers have by restricting access to PrEP therapy. Barriers to PrEP therapy for at-risk individuals can greatly increase the risk of HIV infection, which in turn increases health care costs and negatively affects outcomes across the US.

There is significant value in removing barriers to PrEP and in encouraging adherence to treatment/prevention guidelines. Insurers/payers, pharmacists, manufacturers, and providers all play a role in helping to stop the HIV epidemic.  By identifying barriers to PrEP for HIV, stakeholders can create programs to increase access for the at-risk people who most need protection. Insurers/payers have a particular and immediate opportunity to acknowledge and address the impact of coverage restrictions on PrEP for HIV within their own populations. 

Gary Oderda, PharmD, MPH. College of Pharmacy, University of Utah. Goderda@pharm.utah.edu, 801-581-6257.

Joseph Biskupiak, PhD, MBA. College of Pharmacy, University of Utah. Joseph.Biskupiak@pharm.utah.edu, 801-585-5249.

Diana Brixner, PhD, RPh. College of Pharmacy, University of Utah. Diana.Brixner@utah.edu, 801-581-3182.