Opportunities for identifying and addressing barriers to HIV PrEP

HIV preexposure prophylaxis (PrEP) has a critical role in ending the HIV epidemic in the United States. This article will explore the current state of HIV PrEP uptake in this country and describe measures that can help to both increase awareness of HIV PrEP and improve adherence to this important prevention strategy.

High-risk behaviors related to, and populations affected by, HIV infection

In the United States, an estimated 1.2 million people aged 13 years or older were living with HIV in 2019; an estimated 13.3% of these patients, however, had not received a diagnosis.¹ Behaviors that increase the risk of acquiring HIV infection include sexual activity with an infected person and injection of illicit drugs.^2-4 Individuals who inject illicit drugs and have an HIV-positive injecting partner or share injection equipment are at highest risk of HIV acquisition.²

Although HIV infection can occur in persons of any age, gender, race, ethnicity or sexual orientation, HIV disproportionately affects gay and bisexual men and other men who have sex with men (MSM) in the United States.³ Members of racial and ethnic minority communities are also highly affected. In the United States, 42.1% of new HIV infections occurred in Black populations in 2019, a rate that was more than eight times higher than that reported among White populations (5%).¹ Individuals with Hispanic/Latino ethnicity comprised 21.7% of newly infected people.¹

HIV PrEP

Clinical guidelines

HIV PrEP involves taking medication to prevent HIV infection. Clinical practice guidelines issued in 2021 by the Centers for Disease Control and Prevention (CDC) recommend informing all sexually active adults and adolescents about HIV PrEP, screening all sexually active patients for an HIV PrEP indication and screening all adult patients for use of injectable illicit drugs. The guidelines also recommend that clinicians discuss HIV PrEP with sexually active patients and prescribe it to those who are at risk of HIV infection or who request a prescription. Similarly, clinicians should prescribe HIV PrEP to patients who inject illicit drugs and are at risk for acquiring HIV or who request it.²

Oral PrEP

Two drug combinations are recommended by the CDC for oral HIV PrEP.² In 2012, Truvada, a combination pill composed of emtricitabine and tenofovir disoproxil fumarate (F/TDF), became the first FDA-approved HIV PrEP agent.⁵ Daily F/TDF is indicated for adult and adolescent men and women weighing at least 35 kilograms; its use is recommended for those who report either illicit drug injection or sexual practices that place them at risk of acquiring HIV infection.^2,6 Another oral pill, Descovy, gained FDA approval for HIV PrEP in 2019.⁷ This combination of emtricitabine and tenofovir alafenamide (F/TAF) is indicated for daily oral use in transgender women and in sexually active men or adolescents weighing at least 35 kilograms; it is also recommended for those who report sexual practices that place them at risk of acquiring HIV.^2,8 The effectiveness of F/TAF has not been studied in individuals at risk of HIV infection from receptive vaginal sex, so it is not recommended in this population.^2,8

Long-acting, injectable PrEP

In December 2021, the FDA approved the first injectable option for HIV PrEP.⁹ Apretude (cabotegravir; CAB) is a long-acting, injectable drug indicated for adults and adolescents who weigh at least 35 kilograms; its use is recommended in those who report sexual practices that place them at risk of acquiring HIV.^2,10 The CDC recommends that CAB be given, as indicated, every two months by injection into the gluteal muscle with an optional oral four-week lead-in.^2,10 Intramuscular (IM) CAB therapy may be appropriate for patients who have significant renal disease, difficulty in adhering to oral HIV PrEP or a preference for receiving injections every two months versus using oral PrEP.² For patients taking oral HIV PrEP, laboratory tests recommended before or during PrEP use include estimated creatine clearance, hepatitis B-virus serology and lipid panel testing; however, these tests are not required for patients taking CAB for HIV PrEP.² Unlike oral HIV PrEP medications, CAB can be taken by patients with severe renal impairment or end-stage renal disease.^6,8,10

IM CAB: Clinical studies

IM CAB was evaluated in clinical studies that involved a wide range of participants, including cisgender women (HPTN 084; NCT03164564) and cisgender MSM and transgender women who have sex with men (HPTN 083; NCT02720094).^11,12

HPTN 083 was a phase 2b/3, international, multicenter, double-blind, randomized controlled trial (RCT) that examined the safety and efficacy of IM CAB injection administered every eight weeks versus daily oral F/TDF given to adult cisgender MSM and transgender women who have sex with men. Incidence of HIV infection was lower in the CAB arm (n = 2,282) than in the F/TDF arm (n = 2,284; 0.41 vs. 1.22 per 100 person-years, respectively), and the risk of infection was 66% lower in the CAB arm than in the F/TDF arm (hazard ratio, or HR, 0.34; 95% confidence interval, or CI, 0.18-0.62; p-value < .001). The safety population included 4,562 patients (CAB arm, 2,280 patients; F/TDF arm, 2,202 patients). In this population, 92.5% reported side effects of grade two or higher, 32.7% reported side effects of grade three or higher and 5.3% reported serious side effects, with similar frequencies of events noted across the two groups. Among patients who received active CAB injections, 2.4% of patients (50 of 2,117 patients) discontinued injections because of injection-related side effects.¹²

HPTN 084 was an RCT that evaluated IM CAB versus oral F/TDF given in three phases to 3,224 sexually active cisgender women.^11,12 Among the 1,614 women in the CAB arm, the incidence of HIV infection was lower (0.2 per 100 person-years; 95% CI, 0.06-0.52) than that recorded among the 1,610 women in the F/TDF arm (1.86 per 100 person-years; 95% CI, 1.3-2.57).¹¹ Overall, women in the CAB group had an 89% lower risk of HIV infection than did women in the F/TDF group (HR, 0.11; 95% CI, 0.01-0.31; p-value = .000027). Any site reaction was experienced by 32% of patients in the CAB arm and 9% of patients in the F/TDF arm; reactions of grade two or higher were noted among 7% and 1% of patients, respectively, and there were no discontinuations due to injection-site reactions in either study arm.¹¹

Importance of adherence

Adherence to oral HIV PrEP is critical to prevent HIV acquisition.2 For patients who may struggle to achieve high adherence to oral HIV PrEP, IM CAB provides an alternate option. Rather than taking a daily pill, patients need to receive only one injection of CAB every two months. The results of clinical trials have shown that IM CAB provides 66% to 89% higher efficacy than does oral F/TDF.^2,11,12

Managed care considerations

In 2019, substantial evidence that PrEP could reduce risk of HIV acquisition via sexual activity or illicit drug injection led to a U.S. Preventive Services Task Force (USPSTF) A rating for the recommendation that it be offered to persons at high risk of HIV infection.⁴ The USPSTF guidelines are currently being updated, and injectable CAB was not yet approved by the FDA when the 2019 version was released. According to the provisions of the Affordable Care Act (ACA) part 47, this A rating requires most insurers to cover PrEP with no cost-sharing.¹³ No-cost coverage must include not only medication but also counseling (including for adherence, risk reduction and mental health counseling) and the laboratory testing and office visits necessary for initiation or continuation of PrEP use.¹³

Per ACA part 47, plans and issuers are allowed to employ reasonable medical management techniques regarding HIV PrEP coverage, which may include no-cost coverage of generic PrEP but imposition of cost-sharing on the equivalent branded version. If a patient’s healthcare provider deems use of the covered drug to be medically inappropriate, plans and issuers must provide a mechanism to waive cost-sharing for a more appropriate medication.¹³ For individuals who lack prescription drug coverage, the U.S. Department of Health and Human Services has made F/TDF and F/TAF available free of charge through the Ready, Set, PrEP program.²

PrEP uptake: Current status, barriers and opportunities

As of 2018, of nearly 1.2 million people in the United States who had indications for HIV PrEP therapy, only approximately 220,00 individuals received a prescription.² The reasons for this relatively low uptake of HIV PrEP are multifactorial. A review of literature published from 2016 to 2019 identified the following key barriers: low awareness of HIV PrEP among providers and patients, especially those individuals at risk for or living with HIV; low perception of personal HIV risk; social stigma associated with PrEP use; provider bias (whether implicit racial/ethnic prejudice or bias against LGBTQ+ patients); patient distrust of the healthcare system; lack of access to medical care or financial assistance; and provider and patient concerns about side effects and medication interactions.¹⁴

One method for increasing uptake of HIV PrEP is to facilitate discussion of PrEP between healthcare providers and patients.² This includes taking sexual histories of patients, which can help identify patients who are at risk for HIV infection and who may benefit from HIV PrEP. This method also includes providing information about PrEP so patients can respond openly to risk assessment questions and discuss PrEP with others who may benefit from its use.²

To promote adherence, providers should establish trust and bidirectional communication with their patients who start HIV PrEP. Providers should stress the need for adherence, educate patients on potential medication side effects, help create dosing schedules, identify and address barriers to adherence, and monitor HIV PrEP adherence in a nonjudgmental manner. A multidisciplinary approach can also help. The 2021 CDC PrEP guidelines emphasize that a care team of healthcare professionals (e.g., physicians, nurses, pharmacists) working together can improve a patient’s HIV PrEP medication adherence.²

Conclusions

PrEP has a critical role to play in ending the HIV epidemic in the United States. Efforts should be focused on preventing infection via expanded awareness of, and access and adherence to, HIV PrEP for everyone at risk of sexual or injection-acquired infection. The 2021 FDA approval of an injectable option for HIV PrEP provides clinicians and patients with an effective therapeutic choice that does not require remembering to take a pill every day. In addition, to promote widespread HIV PrEP use, it is crucial to address barriers that contribute to lack of patient access or withdrawal from PrEP care.

REFERENCES

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    Department of Labor. July 19, 2021. Accessed March 30, 2022. https://www.dol.gov/sites/dolgov/files/EBSA/about-ebsa/our-activities/resource-center/faqs/aca-part-47.pdf
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