Outcomes of switching from protease inhibitor-based antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically suppressed adults with nucleos(t)ide analogue resistance- a phase IV randomised, open-label study (PIBIK study)

被引：0

作者：

Iwuji, Collins ^{[1
,2
]}

Waters, Laura ^{[3
]}

Milinkovic, Ana ^{[4
]}

Orkin, Chloe ^{[5
,6
]}

Fox, Julie ^{[7
]}

Post, Frank ^{[8
]}

Perry, Nicky ^{[9
]}

Bruce, Chloe ^{[10
]}

Dailey, Natalie ^{[10
]}

To, Ye ^{[10
]}

Bremner, Stephen ^{[10
,11
]}

Churchill, Duncan ^{[9
]}

Geretti, Anna Maria ^{[12
,13
,14
]}

机构：

[1] Univ Sussex, Brighton & Sussex Med Sch, Dept Global Hlth & Infect, Brighton BN1 9PX, England

[2] Africa Hlth Res Inst, Kwa Zulu, South Africa

[3] Cent & Northwest London NHS Fdn Trust, Mortimer Market Ctr, London, England

[4] Chelsea & Westminster Hosp NHS Fdn Trust, London, England

[5] Queen Mary Univ London, Blizard Inst, Fac Med & Dent, London, England

[6] Barts Hlth NHS Trust, London, England

[7] Guys & St ThomasNHS Fdn Trust, London, England

[8] Kings Coll Hosp NHS Fdn Trust, London, England

[9] Univ Hosp Sussex NHS Fdn Trust, London, England

[10] Univ Sussex, Brighton & Sussex Clin Trials Unit, Brighton, England

[11] Univ Sussex, Brighton & Sussex Med Sch, Dept Primary Care & Publ Hlth, Brighton, England

[12] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy

[13] Royal Free London NHS Fdn Trust North Mid, London, England

[14] Kings Coll London, Sch Immun & Microbial Sci, London, England

来源：

VIROLOGY JOURNAL | 2025年 / 22卷 / 01期

关键词：

HIV; Drug resistance; Archive; Bictegravir; Tenofovir alafenamide; Integrase strand transfer inhibitor; Boosted protease inhibitor; Switch; TENOFOVIR DISOPROXIL FUMARATE; NON-INFERIORITY; CARDIOVASCULAR-DISEASE; HIV-1; INFECTION; DOUBLE-BLIND; MULTICENTER; DOLUTEGRAVIR; K65R; EMTRICITABINE; LAMIVUDINE;

D O I：

10.1186/s12985-025-02648-3

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

BackgroundThere are limited data on how historical nucleoside reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs) other than M184V/I, affect the activity of B/F/TAF. We evaluated the outcomes of switching virologically suppressed (HIV-1 RNA < 50 copies/mL) individuals harbouring major RAMs from boosted protease inhibitor (bPI)-based therapy to B/F/TAF. MethodsParticipants had various historical genotypic patterns including M184V/I, <= 2 thymidine analogue mutations (TAMs), and other NRTI RAMs (NAMs), and no integrase resistance. Baseline RAMs were explored by retrospective sequencing of cellular HIV-1 DNA. Participants were randomised (1:1) to switching to B/F/TAF either immediately or after 24 weeks. The primary outcome was the proportion of participants maintaining virological suppression (pure virologic response) at week-24; secondary outcomes were proportion of participants with virological suppression at week-48, pre-specified safety measures, and treatment-emergent resistance. ResultsHistorically, 21/72 (29.2%) participants had M184V/I, 5 (6.9%) M184V/I + 1 NAM, 31 (43.1%) 1 TAM +/- M184V/I +/- 1 NAM, and 15 (20.8%) 2 TAMs +/- M184V/I +/- 1 NAM. At week-24, proportions maintaining virological suppression were 33/33 (100%) on B/F/TAF vs. 38/39 (97.4%) on bPI (difference 2.6%; 95% CI -2.4%, 7.5%). Drug-related adverse events (AEs) were reported in 10/33 (30.3%) vs. 1/39 (2.6%), respectively. The immediate switch arm had improved lipid parameters but increased HbA1c and weight. Virological suppression was maintained at week-48. There were six discontinuations; four on B/F/TAF were drug-related and the two on bPI were not drug-related. ConclusionsHistorical NRTI resistance did not compromise the effectiveness of B/F/TAF in virologically suppressed adults. 12% experienced treatment-limiting AEs after switching. RegistrationEudraCT no: 2018-004732-30

引用

页数：11

共 31 条

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Pozniak, Anton
Markowitz, Martin
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Stellbrink, Hans-Juergen
Antela, Antonio
Domingo, Pere
Girard, Pierre-Marie
Henry, Keith
Thai Nguyen
Piontkowsky, David
Garner, Will
White, Kirsten
Guyer, Bill
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[22] Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial
Ramgopal, Moti N.
Castagna, Antonella
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Sims, James
Di Perri, Giovanni
Sutton, Kenneth
Sutherland-Phillips, Denise
Berni, Alessandro
Latham, Christine L.
Zhang, Feifan
D'Amico, Ronald
Bernaldez, Miguel Pascual
Van Solingen-Ristea, Rodica
Van Eygen, Veerle
Patel, Parul
Chounta, Vasiliki
Spreen, William R.
Garges, Harmony P.
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Perez-Valero, I.
Llibre, J. M.
Pulido, F.
Molina, J-M
Esser, S.
McNicholl, I.
Lorgeoux, R-P
Piontkowsky, D.
Sathia, L.
Haubrich, R.
HIV MEDICINE, 2018, 19 : S21 - S21
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Maggiolo, Franco
Rizzardini, Giuliano
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Ong, Edmund
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[27] Week 48 results of EMERALD: a Phase 3, randomised, non-inferiority study evaluating the efficacy and safety of switching from boosted-protease inhibitors (bPI) plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) regimens to the once daily (QD), single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in virologically suppressed, HIV-1-infected adults
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Molina, J-M
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