Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial

Mayer, Kenneth H.; Molina, Jean‐Michel; Thompson, Melanie; Anderson, Peter L.; Mounzer, Karam; Wet, Joss J De; DeJesus, Edwin; Jessen, Heiko; Grant, Robert M.; Ruane, Peter; Wong, Pamela; Ebrahimi, Ramin; Zhong, Lijie; Mathias, Anita; Callebaut, Christian; Collins, Sean E; Das, Moupali; McCallister, Scott; Brainard, Diana M.; Brinson, Cynthia; Clarke, Amanda; Coll, Pep; Post, Frank A.; Hare, C. Bradley

doi:10.1016/s0140-6736(20)31065-5

Cited by 286 publications

(289 citation statements)

References 59 publications

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“…Likewise, this was a key area for investigation in the DISCOVER trial, which compared F/TDF and F/TAF for PrEP. In that study, F/TAF was associated with improved maintenance of BMD and renal function versus decreases in both BMD and eGFR in the F/TDF arm at the end of the 96-week treatment period [14].…”

Section: Introductionmentioning

confidence: 90%

“…Emtricitabine/tenofovir disoproxil fumarate (Truvada Ò ; F/TDF) [5-7, 12, 13] was approved in 2012, and is indicated for PrEP to reduce the risk of sexually acquired HIV-1 in adults at risk [11]. Emtricitabine/tenofovir alafenamide (Descovy Ò ; F/TAF) [14] was approved in 2019 for adults and adolescents at risk, excluding individuals at risk from receptive vaginal sex, a population that has not yet been studied with F/TAF [10].…”

Section: Introductionmentioning

confidence: 99%

“…Clinical and real-world studies have demonstrated the efficacy of F/TDF in adults and adolescents at risk of HIV infection; the studies included cisgender men who have sex with men (MSM), people who inject drugs (PWID), transgender women, and heterosexual couples in which one partner was living with HIV [5-7, 12, 13, 15, 16]. The efficacy and safety of F/TAF PrEP in cisgender men and transgender women who have sex with men (C 18 years of age) has been investigated and compared with F/TDF in the Phase 3 DISCOVER study, consisting of a 96-week randomized, double-blind period (which has been completed), and a 48-week open-label extension (which is ongoing) [14]. The results of the DISCOVER study demonstrated that F/TAF was non-inferior to F/TDF for the prevention of HIV at the primary analysis (when 100% of participants reached 48 weeks of followup and 50% reached 96 weeks), and also when all participants reached 96 weeks, indicating that the two medications have comparable efficacy at over 99% [14,17].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In addition to the proven efficacy of F/TDF and F/TAF, clinical studies have demonstrated well-tolerated safety profiles for the two medications when used as PrEP [12][13][14]. There are nevertheless important differences between F/TDF and F/TAF in terms of bone and renal safety [14]. The use of F/TDF has been associated with notable decreases in bone mineral density (BMD) and renal function [as measured by estimated glomerular filtration rate (eGFR)] both in individuals with HIV and in individuals who were HIV negative using PrEP [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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

Fields

Tung

2021

Infect Dis Ther

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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 Ò ; F/TDF) was approved by the US Food and Drug Administration in 2012, followed by emtricitabine/tenofovir alafenamide (Descovy Ò ; 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.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Fields

Tung

2021

Infect Dis Ther

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Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Gandhi

Hoy

et al. 2020

JAMA

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362

227

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ImportanceData on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices.ObjectiveTo evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV.Evidence ReviewNew evidence was collected since the previous International Antiviral (formerly AIDS) Society–USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations.FindingsFrom 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic.Conclusion and RelevanceAdvances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.

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Preexposure Prophylaxis to Prevent Acquisition of HIV

Barry,

Nicholson,

Silverstein

et al. 2023

JAMA

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ImportanceAn estimated 1.2 million persons in the US currently have HIV, and more than 760 000 persons have died of complications related to HIV since the first cases were reported in 1981. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority.ObjectiveThe US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of preexposure prophylaxis with antiretroviral therapy for the prevention of HIV acquisition, and the diagnostic accuracy of risk assessment tools to identify persons at increased risk of HIV acquisition.PopulationAdolescents and adults who do not have HIV and are at increased risk of HIV.Evidence AssessmentThe USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV.RecommendationThe USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. (A recommendation)

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Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial

Cited by 286 publications

References 59 publications

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

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

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Preexposure Prophylaxis to Prevent Acquisition of HIV

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