Patient-Focused Selection of PrEP Medication for Individuals at Risk of HIV: A Narrative Review

Abstract

Pre-exposure prophylaxis (PrEP) medication is a key component of the HIV prevention strategy in the US, which has been demonstrated to be highly effective in preventing HIV acquisition among individuals at risk. Two PrEP medications are currently approved: emtricitabine/tenofovir disoproxil fumarate (Truvada^®; F/TDF) was approved by the US Food and Drug Administration in 2012, followed by emtricitabine/tenofovir alafenamide (Descovy^®; F/TAF) in 2019. An ongoing randomized, double-blind, Phase 3 study (DISCOVER) demonstrated that F/TAF had non-inferior efficacy to F/TDF. While both medications have been found to be efficacious and well tolerated, several studies have identified that important differences exist with regards to pharmacokinetics, bone and renal safety profiles, and other factors. In this narrative review, we conducted a comprehensive evaluation of the populations at risk of HIV who may also be affected by, or at risk of, bone or renal conditions. We reviewed the safety profiles of F/TDF and F/TAF to develop an evidence-based algorithm for selecting the appropriate PrEP medication, based on biological, behavioral, and health characteristics of an individual at risk of HIV, and considered how the choice of PrEP medication may or may not compound safety concerns for these individuals. We identified that the introduction of F/TAF provides a valuable alternative to F/TDF, allowing the personalization of PrEP. F/TAF may be the preferred medication for cisgender men and transgender women at risk of HIV infection who are predisposed to, or already have, bone or renal conditions. While the approval of F/TAF is the first step in personalization of PrEP, additional options are still warranted to help accommodate the wide spectrum of individuals at risk of HIV with different lifestyles, medical histories, preferences, and requirements.

Keywords: Bone; Decision making; HIV prevention; Kidney; Personalized medicine; Pre-exposure prophylaxis; Preference; Renal; Tenofovir alafenamide; Tenofovir disoproxil fumarate.

Fig. 1

Algorithm for choosing PrEP. ACEi angiotensin-converting enzyme inhibitor, AE adverse event, ARB angiotensin receptor blocker, BMI body mass index, CKD chronic kidney disease, CVD cardiovascular disease, F/TAF emtricitabine/tenofovir alafenamide, F/TDF emtricitabine/tenofovir disoproxil fumarate, MSM men who have sex with men, NSAID non-steroidal anti-inflammatory drug, PrEP pre-exposure prophylaxis. ^aIf no significant drug–drug interactions. ^bEligibility is limited to MSM who have infrequent sex, are able to plan for sex at least 2 h in advance, and do not have chronic hepatitis B infection. ^cF/TDF is currently not approved for on-demand dosing. ^dIncluding psychotropic medications, NSAIDs, ACEi/ARBs, certain antibiotics, certain chemotherapies.^eIncluding corticosteroids. ^fWeight gain has been observed among individuals using both F/TAF and F/TDF, with slightly less weight gain among those on F/TDF, which may be a factor to consider when discussing PrEP options

Fig. 2

Markers of renal function in individuals ≥ 50 years of age using F/TAF or F/TDF for PrEP (DISCOVER study) (reproduced with permission from [17]). Cr creatinine, eGFR_CG estimated glomerular filtration rate (based on the Cockcroft–Gault equation), F/TAF emtricitabine/tenofovir alafenamide, F/TDF emtricitabine/tenofovir disoproxil fumarate, PrEP pre-exposure prophylaxis, RBP retinol binding protein, β2M β2 microglobulin. Median changes from baseline in (a) eGFR_CG and (b), (c) proximal tubular protein to Cr ratios: (b) RBP:Cr ratio and (c) β2M:Cr ratio. p values at 96 weeks are derived from the Van Elteren test stratified by baseline F/TDF for PrEP to compare the two study arms

Fig. 3

BMD at 96 weeks in individuals using F/TAF or F/TDF for PrEP (DISCOVER study) (reproduced with permission from [17]). BMD bone mineral density, F/TAF emtricitabine/tenofovir alafenamide, F/TDF emtricitabine/tenofovir disoproxil fumarate, PrEP pre-exposure prophylaxis. Proportion of participants with ≥ 3% change in BMD from baseline in (a) spine and (b) hip. All p values are based on dichotomized response from Cochran–Mantel–Haenszel test for nominal data (general association statistic), adjusting for baseline F/TDF for PrEP