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

[1] Switching to bictegravir/emtricitabine/tenofovir alafenamide single tablet regimen from boosted protease inhibitor-based ART in virologically suppressed adults with HIV-1 harbouring drug resistance: a phase IV randomised, open-label pilot study (PIBIK study)
Iwuji, C.
Waters, L.
Milinkovic, A.
Orkin, C.
Perry, N.
Dailey, N.
To, Y.
Bremner, S.
Geretti, A.
Churchill, D.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, 2022, 25 : 89 - 90
[2] Switching to bictegravir/ emtricitabine/tenofovir alafenamide single tablet regimen from boosted protease inhibitor-based ART in virologically suppressed adults with HIV-1 harbouring drug resistance - A phase IV randomized, open-label pilot study (PIBIK study)
Iwuji, C.
Waters, L.
Milinkovic, A.
Orkin, C.
Fox, J.
Post, F.
Perry, N.
Bruce, C.
Dailey, N.
To, Y.
Bremner, S.
Geretti, A. M.
Churchill, D.
HIV MEDICINE, 2023, 24 : 681 - 683
[3] A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naive, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial
Iwuji, Collins C.
Churchill, Duncan
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Bruce, Chloe
Waters, Laura
Orkin, Chloe
Geretti, Anna Maria
BMC INFECTIOUS DISEASES, 2020, 20 (01)
[4] A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial
Collins C. Iwuji
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Chloe Orkin
Anna Maria Geretti
BMC Infectious Diseases, 20
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LANCET HIV, 2018, 5 (07): : E347 - E356
[7] Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged >65 or older: week 48 results from a phase 3b, open-label trial
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HIV MEDICINE, 2020, 21 : 17 - 17
[8] Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged>65 or older: week 48 results from a phase 3b, open-label trial
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HIV MEDICINE, 2021, 22 : 33 - 34
[10] Switching to Fixed-Dose Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF) in Virologically Suppressed HIV-1 Infected Women: A Randomized, Open-Label, Multicenter, Active-Controlled, Phase 3, Noninferiority Trial
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Martin, Hal
Makadzange, Tariro
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2019, 82 (03) : 321 - 328

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