Abstract
Objectives: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects. Methods: Treatment-experienced individuals starting an INSTI-based regimen during 2012–2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥1000 copies/mL or two ≥50 copies/ml or one VL measurement ≥50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated. Results: Of 13560 treatments analysed, 4284 were from INSTI-naïve, non-viraemic (IN-NV) individuals, 1465 were from INSTI-naïve, viraemic (IN-V) individuals, 6016 were from INSTI-experienced, non-viraemic (IE-NV) individuals and 1795 were from INSTI-experienced, viraemic (IE-V) individuals. Major INSTI drug resistance mutations (DRMs) were previously detected in 4/519 (0.8%) IN-NV, 3/394 (0.8%) IN-V, 7/1510 (0.5%) IE-NV and 25/935 (2.7%) IE-V individuals. The 1-year estimated probabilities of VF were 3.1% [95% confidence interval (CI): 2.5–3.8] in IN-NV, 18.4% (95% CI: 15.8–21.2) in IN-V, 4.2% (95% CI: 3.6–4.9) in IE-NV and 23.9% (95% CI: 20.9–26.9) in IE-V subjects. The 1-year estimated probabilities of INSTI discontinuation were 12.1% (95% CI: 11.1–13.0) in IN-NV, 19.6% (95% CI: 17.5–21.6) in IN-V, 10.8% (95% CI: 10.0–11.6) in IE-NV and 21.7% (95% CI: 19.7–23.5) in IE-V subjects. Conclusions: Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.
| Original language | English |
|---|---|
| Pages (from-to) | 774-789 |
| Number of pages | 16 |
| Journal | HIV Medicine |
| Volume | 23 |
| Issue number | 7 |
| Early online date | 24 Feb 2022 |
| DOIs | |
| Publication status | Published - Aug 2022 |
Keywords
- dolutegravir
- effectiveness
- elvitegravir
- HIV
- INSTI
- integrase strand transfer inhibitors
- raltegravir
- treatment-experienced
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Rossetti, B., Fabbiani, M., Di Carlo, D., Incardona, F., Abecasis, A., Gomes, P., Geretti, A. M., Seguin-Devaux, C., Garcia, F., Kaiser, R., Modica, S., Shallvari, A., Sönnerborg, A., Zazzi, M., Abecasis, A., Bobkova, M., Fabbiani, M., Garcia, F., Geretti, A. M., ... EuResist Network, INTEGRATE study group (2022). Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. HIV Medicine, 23(7), 774-789. https://doi.org/10.1111/hiv.13262
Rossetti, Barbara ; Fabbiani, Massimiliano ; Di Carlo, Domenico et al. / Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. In: HIV Medicine. 2022 ; Vol. 23, No. 7. pp. 774-789.
@article{1f8522bc82724f3eb2713638339b3327,
title = "Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe",
abstract = "Objectives: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects. Methods: Treatment-experienced individuals starting an INSTI-based regimen during 2012–2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥1000 copies/mL or two ≥50 copies/ml or one VL measurement ≥50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated. Results: Of 13560 treatments analysed, 4284 were from INSTI-na{\"i}ve, non-viraemic (IN-NV) individuals, 1465 were from INSTI-na{\"i}ve, viraemic (IN-V) individuals, 6016 were from INSTI-experienced, non-viraemic (IE-NV) individuals and 1795 were from INSTI-experienced, viraemic (IE-V) individuals. Major INSTI drug resistance mutations (DRMs) were previously detected in 4/519 (0.8%) IN-NV, 3/394 (0.8%) IN-V, 7/1510 (0.5%) IE-NV and 25/935 (2.7%) IE-V individuals. The 1-year estimated probabilities of VF were 3.1% [95% confidence interval (CI): 2.5–3.8] in IN-NV, 18.4% (95% CI: 15.8–21.2) in IN-V, 4.2% (95% CI: 3.6–4.9) in IE-NV and 23.9% (95% CI: 20.9–26.9) in IE-V subjects. The 1-year estimated probabilities of INSTI discontinuation were 12.1% (95% CI: 11.1–13.0) in IN-NV, 19.6% (95% CI: 17.5–21.6) in IN-V, 10.8% (95% CI: 10.0–11.6) in IE-NV and 21.7% (95% CI: 19.7–23.5) in IE-V subjects. Conclusions: Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.",
keywords = "dolutegravir, effectiveness, elvitegravir, HIV, INSTI, integrase strand transfer inhibitors, raltegravir, treatment-experienced",
author = "Barbara Rossetti and Massimiliano Fabbiani and {Di Carlo}, Domenico and Francesca Incardona and Ana Abecasis and Perpetua Gomes and Geretti, {Anna Maria} and Carole Seguin-Devaux and Federico Garcia and Rolf Kaiser and Sara Modica and Adrian Shallvari and Anders S{\"o}nnerborg and Maurizio Zazzi and A. Abecasis and M. Bobkova and M. Fabbiani and F. Garcia and Geretti, {A. M.} and P. Gomes and F. Incardona and R. Kaiser and R. Paredes and B. Rossetti and M. Sayan and A. S{\"o}nnerborg and Vandamme, {A. M.} and M. Zazzi and {EuResist Network, INTEGRATE study group}",
note = "Funding Information: The INTEGRATE project received an unconditioned grant from Gilead Sciences Europe Ltd. This study was also funded by the Swedish Research Council (2016‐01675, to AS), the European Union by the CARE H2020 project (under grant agreement no. 825673) and Stockholm County Council (ALF 20190451 and CIMED 20200645; to AS), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia, Portugal (INTEGRIV Project PTDC/SAU‐INF/31990/20170 and GHTM‐UID/Multi/04413/2013; to AA). Funding Information: The INTEGRATE project received an unconditioned grant from Gilead Sciences Europe Ltd. This study was also funded by the Swedish Research Council (2016-01675, to AS), the European Union by the CARE H2020 project (under grant agreement no. 825673) and Stockholm County Council (ALF 20190451 and CIMED 20200645; to AS), and the Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia, Portugal (INTEGRIV Project PTDC/SAU-INF/31990/20170 and GHTM-UID/Multi/04413/2013; to AA). The INTEGRATE study group: A. Abecasis, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical - Universidade Nova de Lisboa, Lisbon, Portugal M. Bobkova, Gamaleya Federal Center for Epidemiology and Microbiology of Russia C. Seguin-Devaux, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg M. Fabbiani, University Hospital of Siena, Siena, Italy F. Garcia, Hospital Universitario San Cecilio, Granada, Spain A. M. Geretti, University of Liverpool, UK P. Gomes, Laborat{\'o}rio de Biologia Molecular (LMCBM, SPC, CHLO-HEM), Lisbon, Portugal and Centro de Investiga{\c c}{\~a}o Interdisciplinar Egas Moniz (CiiEM), Instituto Universit{\'a}rio Egas Moniz, Caparica, Portugal F. Incardona, EuResist Network, Roma, Italy – IPRO, Roma, Italy R. Kaiser, University of Cologne, Cologne, Germany R. Paredes, Irsicaixa, Spain B. Rossetti, University Hospital of Siena, Siena, Italy M. Sayan, Kocaeli University, Medical Faculty, Turkey A. S{\"o}nnerborg, Karolinska Institutet, Stockholm, Sweden A. M. Vandamme, REGA Institut KU Leuven, Belgium M. Zazzi, University of Siena, Siena, Italy. Publisher Copyright: {\textcopyright} 2022 British HIV Association.",
year = "2022",
month = aug,
doi = "10.1111/hiv.13262",
language = "English",
volume = "23",
pages = "774--789",
journal = "HIV Medicine",
issn = "1464-2662",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "7",
}
Rossetti, B, Fabbiani, M, Di Carlo, D, Incardona, F, Abecasis, A, Gomes, P, Geretti, AM, Seguin-Devaux, C, Garcia, F, Kaiser, R, Modica, S, Shallvari, A, Sönnerborg, A, Zazzi, M, Abecasis, A, Bobkova, M, Fabbiani, M, Garcia, F, Geretti, AM, Gomes, P, Incardona, F, Kaiser, R, Paredes, R, Rossetti, B, Sayan, M, Sönnerborg, A, Vandamme, AM, Zazzi, M & EuResist Network, INTEGRATE study group 2022, 'Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe', HIV Medicine, vol. 23, no. 7, pp. 774-789. https://doi.org/10.1111/hiv.13262
Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. / Rossetti, Barbara; Fabbiani, Massimiliano; Di Carlo, Domenico et al.
In: HIV Medicine, Vol. 23, No. 7, 08.2022, p. 774-789.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe
AU - Rossetti, Barbara
AU - Fabbiani, Massimiliano
AU - Di Carlo, Domenico
AU - Incardona, Francesca
AU - Abecasis, Ana
AU - Gomes, Perpetua
AU - Geretti, Anna Maria
AU - Seguin-Devaux, Carole
AU - Garcia, Federico
AU - Kaiser, Rolf
AU - Modica, Sara
AU - Shallvari, Adrian
AU - Sönnerborg, Anders
AU - Zazzi, Maurizio
AU - Abecasis, A.
AU - Bobkova, M.
AU - Fabbiani, M.
AU - Garcia, F.
AU - Geretti, A. M.
AU - Gomes, P.
AU - Incardona, F.
AU - Kaiser, R.
AU - Paredes, R.
AU - Rossetti, B.
AU - Sayan, M.
AU - Sönnerborg, A.
AU - Vandamme, A. M.
AU - Zazzi, M.
AU - EuResist Network, INTEGRATE study group
N1 - Funding Information:The INTEGRATE project received an unconditioned grant from Gilead Sciences Europe Ltd. This study was also funded by the Swedish Research Council (2016‐01675, to AS), the European Union by the CARE H2020 project (under grant agreement no. 825673) and Stockholm County Council (ALF 20190451 and CIMED 20200645; to AS), and the Fundação para a Ciência e Tecnologia, Portugal (INTEGRIV Project PTDC/SAU‐INF/31990/20170 and GHTM‐UID/Multi/04413/2013; to AA). Funding Information:The INTEGRATE project received an unconditioned grant from Gilead Sciences Europe Ltd. This study was also funded by the Swedish Research Council (2016-01675, to AS), the European Union by the CARE H2020 project (under grant agreement no. 825673) and Stockholm County Council (ALF 20190451 and CIMED 20200645; to AS), and the Fundação para a Ciência e Tecnologia, Portugal (INTEGRIV Project PTDC/SAU-INF/31990/20170 and GHTM-UID/Multi/04413/2013; to AA). The INTEGRATE study group: A. Abecasis, Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical - Universidade Nova de Lisboa, Lisbon, Portugal M. Bobkova, Gamaleya Federal Center for Epidemiology and Microbiology of Russia C. Seguin-Devaux, Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg M. Fabbiani, University Hospital of Siena, Siena, Italy F. Garcia, Hospital Universitario San Cecilio, Granada, Spain A. M. Geretti, University of Liverpool, UK P. Gomes, Laboratório de Biologia Molecular (LMCBM, SPC, CHLO-HEM), Lisbon, Portugal and Centro de Investigação Interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, Portugal F. Incardona, EuResist Network, Roma, Italy – IPRO, Roma, Italy R. Kaiser, University of Cologne, Cologne, Germany R. Paredes, Irsicaixa, Spain B. Rossetti, University Hospital of Siena, Siena, Italy M. Sayan, Kocaeli University, Medical Faculty, Turkey A. Sönnerborg, Karolinska Institutet, Stockholm, Sweden A. M. Vandamme, REGA Institut KU Leuven, Belgium M. Zazzi, University of Siena, Siena, Italy.Publisher Copyright:© 2022 British HIV Association.
PY - 2022/8
Y1 - 2022/8
N2 - Objectives: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects. Methods: Treatment-experienced individuals starting an INSTI-based regimen during 2012–2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥1000 copies/mL or two ≥50 copies/ml or one VL measurement ≥50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated. Results: Of 13560 treatments analysed, 4284 were from INSTI-naïve, non-viraemic (IN-NV) individuals, 1465 were from INSTI-naïve, viraemic (IN-V) individuals, 6016 were from INSTI-experienced, non-viraemic (IE-NV) individuals and 1795 were from INSTI-experienced, viraemic (IE-V) individuals. Major INSTI drug resistance mutations (DRMs) were previously detected in 4/519 (0.8%) IN-NV, 3/394 (0.8%) IN-V, 7/1510 (0.5%) IE-NV and 25/935 (2.7%) IE-V individuals. The 1-year estimated probabilities of VF were 3.1% [95% confidence interval (CI): 2.5–3.8] in IN-NV, 18.4% (95% CI: 15.8–21.2) in IN-V, 4.2% (95% CI: 3.6–4.9) in IE-NV and 23.9% (95% CI: 20.9–26.9) in IE-V subjects. The 1-year estimated probabilities of INSTI discontinuation were 12.1% (95% CI: 11.1–13.0) in IN-NV, 19.6% (95% CI: 17.5–21.6) in IN-V, 10.8% (95% CI: 10.0–11.6) in IE-NV and 21.7% (95% CI: 19.7–23.5) in IE-V subjects. Conclusions: Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.
AB - Objectives: To explore the effectiveness and durability of integrase strand transfer inhibitor (INSTI)-based regimens in pre-treated subjects. Methods: Treatment-experienced individuals starting an INSTI-based regimen during 2012–2019 were selected from the INTEGRATE collaborative study. The time to virological failure [VF: one measurement of viral load (VL) ≥1000 copies/mL or two ≥50 copies/ml or one VL measurement ≥50 copies/mL followed by treatment change] and to INSTI discontinuation were evaluated. Results: Of 13560 treatments analysed, 4284 were from INSTI-naïve, non-viraemic (IN-NV) individuals, 1465 were from INSTI-naïve, viraemic (IN-V) individuals, 6016 were from INSTI-experienced, non-viraemic (IE-NV) individuals and 1795 were from INSTI-experienced, viraemic (IE-V) individuals. Major INSTI drug resistance mutations (DRMs) were previously detected in 4/519 (0.8%) IN-NV, 3/394 (0.8%) IN-V, 7/1510 (0.5%) IE-NV and 25/935 (2.7%) IE-V individuals. The 1-year estimated probabilities of VF were 3.1% [95% confidence interval (CI): 2.5–3.8] in IN-NV, 18.4% (95% CI: 15.8–21.2) in IN-V, 4.2% (95% CI: 3.6–4.9) in IE-NV and 23.9% (95% CI: 20.9–26.9) in IE-V subjects. The 1-year estimated probabilities of INSTI discontinuation were 12.1% (95% CI: 11.1–13.0) in IN-NV, 19.6% (95% CI: 17.5–21.6) in IN-V, 10.8% (95% CI: 10.0–11.6) in IE-NV and 21.7% (95% CI: 19.7–23.5) in IE-V subjects. Conclusions: Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.
KW - dolutegravir
KW - effectiveness
KW - elvitegravir
KW - HIV
KW - INSTI
KW - integrase strand transfer inhibitors
KW - raltegravir
KW - treatment-experienced
UR - http://www.scopus.com/inward/record.url?scp=85133756731&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35199909
U2 - 10.1111/hiv.13262
DO - 10.1111/hiv.13262
M3 - Article
C2 - 35199909
SN - 1464-2662
VL - 23
SP - 774
EP - 789
JO - HIV Medicine
JF - HIV Medicine
IS - 7
ER -
Rossetti B, Fabbiani M, Di Carlo D, Incardona F, Abecasis A, Gomes P et al. Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. HIV Medicine. 2022 Aug;23(7):774-789. Epub 2022 Feb 24. doi: 10.1111/hiv.13262
