Expansion to adolescents, flexible dosing strategies, innovative delivery models, and long-acting antiretrovirals all help the strategy.
Pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection is a rapidly evolving area of public health. The treatment became available to high-risk individuals in the United States with the approval of the first combination antiretroviral tablet for uninfected adults, emtricitabine-tenofovir disoproxil fumarate (TDF/FTC, Truvada) in 2012.
The efficacy of emtricitabine-tenofovir in preventing HIV infection was established by the iPrEx study, a randomized placebo-controlled international trial of men who have sex with men (MSM) and transgender male-to-female adults; the results demonstrated a 44% reduction in HIV infection among 2499 participants.1 The Partners PrEP study reported similar findings among HIV serodiscordant heterosexual couples prior to universal HIV treatment in Kenya and Uganda; patients were 75% less likely to become infected with daily use of TDF/FTC.2 These findings are consistently demonstrated in controlled and real-world studies, with a 2016 meta-analysis reporting that among studies with an adherence rate > 70%, HIV acquisition was reduced by 70%.3
Despite the established efficacy of daily PrEP, its use among the 1.2 million eligible patients in the United States is relatively low.4,5 Guidelines recommend PrEP for sexually active MSM, heterosexual men and women, and injection drug users at substantial risk of acquiring HIV infection.6 Notably, this population recently expanded with the May 2018 FDA approval of TDF/ FTC for adolescents who weighed at least 35 kg, a change that will be incorporated in future guideline updates.7 A recent national prescription database study suggested that the PrEP-to-need ratio, the number of PrEP users divided by new HIV diagnoses, is 1.8 nationwide.8 Several innovations have been suggested to increase PrEP prescriptions, adherence, and persistence in care among those at risk, including new antiretrovirals, novel health care delivery models, and on-demand regimens.
PrEP prescribing by HIV specialists in the clinical setting presents challenges for patients, including financial and geographic barriers, inadequate numbers of specialists, and limited hours for required quarterly visits and laboratory testing.5 Engaging primary-care clinicians as PrEP providers is a potential way to identify eligible patients and increase use.5 Research suggests that targeted educational programs for primary-care providers may increase prescribing in a cohort that has historically underused PrEP.9,10 Pharmacist-prescribed PrEP under a collaborative practice agreement in the community pharmacy setting is another approach that leverages the expertise of pharmacists and greater accessibility of retail pharmacies. A Seattle-based independent pharmacy recently described a pharmacist-run PrEP clinic that was financially sustainable, with a high 1-year retention rate.11
Telemedicine is also emerging as a promising method of connecting patients to PrEP, allowing them to speak to specialists remotely and in private. A CDC-funded program in Iowa provides pharmacist-prescribed PrEP via telemedicine to patients in rural areas, and data suggest that most patients have persisted with PrEP for at least 6 months.12 Other home-based methods include PrEP@Home, a National Institute of Mental Health—funded study led by researchers at Emory University in Atlanta. The program eliminates in-person PrEP follow-up visits by providing patients with self-collection laboratory testing kits and telemedicine appointments if needed.13 Preliminary results indicate that 85% of participants prefer at-home testing to office visits.13
On-demand dosing has been proposed to encourage PrEP in patients at periodic risk, based on efficacy data from the IPERGAY study that reported an 86% reduction in HIV incidence among MSM compared with the placebo.14 The regimen consists of 2 pills of TDF/FTC taken 2 to 24 hours before sex and a third and fourth pill 24 and 48 hours after the loading dose, respectively.14 IPERGAY is limited by the fact that subjects had relatively high intake of 15 tablets per month, which has been shown to result in TDF concentrations above the efficacy threshold in a majority of patients.15 Pharmacokinetic modelling suggests that less frequent on-demand dosing would still produce effective concentrations, and the findings of a real-world study of French MSM patients who received on-demand PrEP supported an extremely low incidence of HIV.15,16 On-demand dosing is recommended in Australia, Canada, and Western Europe and may eventually become an option for patients in the United States at episodic risk.17-19
Alternatives to TDF/FTC are desired to minimize long-term bone and kidney toxicities.20 Despite initial questions about tenofovir alafenamide (TAF) for PrEP due to low female genitourinary concentrations, data from the DISCOVER study presented at the Conference on Retroviruses and Opportunistic Infections 2019 suggest that TAF/FTC is noninferior to TDF/ FTC in preventing HIV among MSM.21,22 Nonoral and long-acting antiretrovirals are another exciting development expected to improve patient adherence. Options in the pipeline include a long-acting injectable cabotegravir, subdermal TAF implant, and vaginal dapivirine ring.23-25 Favorable preliminary results are available for a monthly dapivirine vaginal ring; a 3-month option and a co-formulation with the contraceptive levonorgestrel are in early-phase studies.23,26 Injectable cabotegravir has been shown to be well tolerated, with 74% of ECLAIR study participants preferring the injection over oral cabotegravir.25,27
HIV PrEP is an integral component of the effort to reduce HIV transmission worldwide. Expansion to adolescents, flexible dosing strategies, innovative PrEP delivery models, and long-acting antiretrovirals all widen the scope and acceptance of PrEP.
Claire Solofra, Ryan Sanok, and Ryan Lindstrom are PharmD candidates at the Medical College of Wisconsin School of Pharmacy in Milwaukee.
Kristen Bunnell, PharmD, is an assistant professor of clinical sciences at the Medical College of Wisconsin School of Pharmacy.
The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied healthcare professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit sidp.org.