The persistence of PrEP: Essential for ending HIV

Approximately 30 years after the beginning of the HIV epidemic, emtricitabine–tenofovir disoproxil fumarate (FTC/TDF; Truvada, Gilead) was approved in 2012 as the first pre-exposure prophylaxis (PrEP) therapy. However, of the 1.2 million Americans eligible for PrEP, only an estimated 70,000 had an active prescription for PrEP as of the end of 2017.¹ In 2019, FTC–tenofovir alafenamide (FTC/TAF; Descovy, Gilead) was approved as a second PrEP therapy option. The PrEP continuum of care includes awareness of risk, uptake of therapy, and adherence and retention in care.² Barriers to adherence and retention in care include forgetfulness, competing priorities, safety concerns, stigma, and lack of a supportive social network.³

It is well known that PrEP adherence is directly related to efficacy.⁴ Thus, a barrier that should be addressed is the ability to remain on PrEP after initiation, referred to as PrEP persistence. PrEP persistence is also defined as the length of time a person continues to refill PrEP prescriptions without an interruption of more than 30 days.⁵

Initiation of PrEP may be a poor measure because the discontinuation of PrEP at 1 month is reported to be as high as 45%.⁶ A study of 11,807 people with commercial insurance and 647 with Medicaid revealed a significant disparity in PrEP persistence.⁵ People with commercial insurance remained on PrEP for a median of 13.7 months (95% CI, 13.3-14.1 months) compared with 6.8 months (95% CI, 6.1-7.6 months) among those on Medicaid. After adjustment for covariates, female sex (hazard ratio [HR], 1.81; 95% CI, 1.6-2.1) and younger age (18-24 years: HR, 2.4; 95% CI, 2.1-2.7) were predictors of nonpersistence.⁵

A separate study of 300 people also showed that age affected PrEP persistence.⁷ In this study, 85% of participants had at least 1 behavior associated with a high risk for HIV acquisition. Of the participants, 178 (59%) were 30 years of age or older, 287 (96%) were men, and 178 (59%) identified as men who have sex with men (MSM).⁷ There were 57 (19%) participants who were not white. After 12 months, 44% of participants were persistent with PrEP. Only 34% attended quarterly follow-up visits. Being age 30 years or older was associated positively with PrEP persistence (odds ratio [OR], 1.04; 95% CI, 1.0-1.1). Additionally, a negative association was found with PrEP persistence and minority group status (OR, 0.33; 95% CI, 0.12-0.83).⁷

Understanding Changes Use

Some people may stop PrEP for appropriate reasons, such as no longer being at high risk for HIV acquisition, but many discontinue due to structural issues. A study of 25 people taking PrEP and 18 providers of PrEP care identified several reasons for the PrEP discontinuation,⁸ including side effects and lack of perceived risk. In addition, a lack of housing caused 1 person to stop therapy. From a provider perspective, there is often a focus on short-term clinical visits rather than long-term PrEP persistence. An analysis of 103 MSM taking PrEP found that 18% attended clinic appointments less often than the 3-month interval recommended by guidelines.⁹ The emergent reported barrier to PrEP adherence was insurance (39%), specifically the need for prior authorization and mail-order pharmacy mandates. In addition, systemic barriers to medical care were reported, such as poor availability of appointments, leading to medical appointment–related barriers.⁹ Removal of these appointment- and insurance-related barriers may help with PrEP persistence.

A systematic review and meta- ethnography of experiences with PrEP use in cisgender men in the United States revealed interventions such as telehealth and pharmacist-prescribed approaches to PrEP distribution might reduce barriers to PrEP uptake and persistence.¹⁰ However, structural interventions were not likely to alleviate barriers in underserved communities. Of interest, a study of approximately 1,000 participants taking PrEP reported that out-of-pocket costs for medication and clinic visits were not barriers to PrEP persistence. In this study, the average quarterly out-of-pocket cost was $34 (median, $5; interquartile range, $0-$25), and those with commercial insurance had higher costs than those without insurance.¹¹ The authors noted that the costs were absolute and not analyzed relative to income, which may have led to a different interpretation of the data.

The introduction of 2-1-1 PrEP dosing, sometimes called “on-demand PrEP,” provided an option for people who don’t want to take medication every day.¹² A study of 140 men who had used the 2-1-1 dosing strategy reported high adherence to the double dose before sexual encounters. However, barriers to using this dosing strategy, such as stigma, cost, and unplanned sexual encounters, were reported.¹² It should be noted that this particular PrEP dosing strategy is currently only recommended by the International Antiretroviral Society-USA for the MSM population.¹³

People taking PrEP may also discontinue therapy due to a low perceived risk for HIV acquisition.¹⁴ This may occur without consultation with a health care provider. Data at the 6- to 12-month mark indicate discontinuations occur even though there is an ongoing risk for HIV acquisition.⁸ In a study of 112 Black ciswomen, PrEP persistence was 18%, with an average of 8.1 months on therapy.¹⁵ This small percentage was mainly attributed to a low perception of risk by participants and health care providers. Perceived and ongoing risk should be discussed at the initiation of therapy to avoid inappropriate discontinuation.¹⁴

While PrEP persistence is an important topic, there will be people for whom it is appropriate to discontinue therapy. It should be noted that major and international guidelines provide differing recommendations on the duration of oral therapy after the last exposure if PrEP discontinuation is desired.¹⁴ Length of therapy should be considered based on the type of exposure, and it varies from 2 to 28 days.¹⁴

PrEP specialized services, navigation, LGBTQIA+ competent providers, and accessible clinic locations may reduce barriers to PrEP persistence. In addition, a comprehensive approach should be used; referrals for substance use, housing, and mental health services should be provided if appropriate.⁹ Other strategies that should be considered include 90-day prescriptions, drop-in clinic visits, and standing orders for laboratory testing. “Same-day” PrEP is also an emerging strategy to avoid delays in PrEP initiation.¹⁶ Data suggest that discontinuation with this strategy occurs at the same rate as standard prescribing practices.

Understanding barriers to the initiation and persistence of PrEP is a critical factor to ending the HIV epidemic. Data on people with specific characteristics continue to expand. New PrEP options will also provide more opportunities for diverse populations. Targeted interventions based on the available data should be implemented to increase PrEP persistence.

By Milena Murray, PharmD, MSc, BCIDP, AAHIVP

References

1. Beymer MR, Holloway IW, Pulsipher C, et al. Current and future PrEP medications and modalities: on-demand, injectables, and topicals. Curr HIV/AIDS Rep. 2019;16(4):349-358.
2. Nunn AS, Brinkley-Rubinstein L, Oldenburg CE, et al. Defining the HIV pre-exposure prophylaxis care continuum. AIDS. 2017;31(5):731-734.
3. Clement ME, Kofron R, Landovitz RJ. Long-acting injectable cabotegravir for the prevention of HIV infection. Curr Opin HIV AIDS. 2020;15(1):19-26.
4. Koss CA, Liu AY, Castillo-Mancilla J, et al. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. AIDS. 2018;32(15):2189-2194.
5. Huang YA, Tao G, Smith DK, et al. Persistence with human immunodeficiency virus pre-exposure prophylaxis in the United States, 2012-2017. Clin Infect Dis. 2021;72(3):379-385.
6. Stankevitz K, Grant H, Lloyd J, et al. Oral preexposure prophylaxis continuation, measurement and reporting. AIDS. 2020;34(12):1801-1811.
7. Keyes J, Crouse EC, DeJesus E, et al. Determinants of pre-exposure prophylaxis (PrEP) persistence in a high-risk population in central Florida. J Investig Med. 2021;69(2):397-401.
8. Laborde ND, Kinley PM, Spinelli M, et al. Understanding PrEP persistence: provider and patient perspectives. AIDS Behav. 2020;24(9):2509-2519.
9. D’Angelo AB, Lopez-Rios J, Flynn AWP, et al. Insurance- and medical provider-related barriers and facilitators to staying on PrEP: results from a qualitative study. Transl Behav Med. 2021;11(2):573-581.
10. Edeza A, Karina Santamaria E, Valente PK, et al. Experienced barriers to adherence to pre-exposure prophylaxis for HIV prevention among MSM: a systematic review and meta-ethnography of qualitative studies. AIDS Care. 2021;33(6):697-705.
11. Furukawa NW, Schneider JA, Coleman ME, et al. Out-of-pocket costs and HIV pre-exposure prophylaxis persistence in a US multicity demonstration project. Health Serv Res. 2020;55(4):524-530.
12. Camp C, Saberi P. Facilitators and barriers of 2-1-1 HIV pre-exposure prophylaxis. PLoS One. 2021;16(5):e0251917.
13. Saag MS, Gandhi RT, Hoy JF, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2020 recommendations of the International Antiviral Society–USA panel. JAMA. 2020;324(16):1651-1669.
14. Rutstein SE, Smith DK, Dalal S, et al. Initiation, discontinuation, and restarting HIV pre-exposure prophylaxis: ongoing implementation strategies. Lancet HIV. 2020;7(10):e721-e730.
15. Pyra M, Johnson AK, Devlin S, et al. HIV pre-exposure prophylaxis use and persistence among black ciswomen: “Women need to protect themselves, period.” J Racial Ethn Health Disparities. 2021 Mar 17: 1-10. doi: 10.1007/s40615-021-01020-9
16. Rowan SE, Patel RR, Schneider JA, et al. Same-day prescribing of daily oral pre-exposure prophylaxis for HIV prevention. Lancet HIV. 2021;8(2):e114-e120.