The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial

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The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals : a randomised, placebo-controlled, double-blind trial. / Rasmussen, Thomas A.; McMahon, James H.; Chang, J. Judy; Audsley, Jennifer; Rhodes, Ajantha; Tennakoon, Surekha; Dantanarayana, Ashanti; Spelman, Tim; Schmidt, Tina; Kent, Stephen J.; Morcilla, Vincent; Palmer, Sarah; Elliott, Julian H.; Lewin, Sharon R.

In: The Lancet HIV, Vol. 5, No. 5, 01.05.2018, p. e221-e230.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Rasmussen, TA, McMahon, JH, Chang, JJ, Audsley, J, Rhodes, A, Tennakoon, S, Dantanarayana, A, Spelman, T, Schmidt, T, Kent, SJ, Morcilla, V, Palmer, S, Elliott, JH & Lewin, SR 2018, 'The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial', The Lancet HIV, vol. 5, no. 5, pp. e221-e230. https://doi.org/10.1016/S2352-3018(18)30040-7

APA

CBE

Rasmussen TA, McMahon JH, Chang JJ, Audsley J, Rhodes A, Tennakoon S, Dantanarayana A, Spelman T, Schmidt T, Kent SJ, Morcilla V, Palmer S, Elliott JH, Lewin SR. 2018. The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial. The Lancet HIV. 5(5):e221-e230. https://doi.org/10.1016/S2352-3018(18)30040-7

MLA

Vancouver

Author

Rasmussen, Thomas A. ; McMahon, James H. ; Chang, J. Judy ; Audsley, Jennifer ; Rhodes, Ajantha ; Tennakoon, Surekha ; Dantanarayana, Ashanti ; Spelman, Tim ; Schmidt, Tina ; Kent, Stephen J. ; Morcilla, Vincent ; Palmer, Sarah ; Elliott, Julian H. ; Lewin, Sharon R. / The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals : a randomised, placebo-controlled, double-blind trial. In: The Lancet HIV. 2018 ; Vol. 5, No. 5. pp. e221-e230.

Bibtex

@article{7eddaaf8708b411b986260a21c334506,
title = "The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial",
abstract = "Background: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. Methods: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per mL at screening and two CD4 counts higher than 350 cells per μL in the previous 24 months including screening. Participants were randomly assigned (1:1) to receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The primary outcome was the change from baseline in frequency of 2-long terminal repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is registered with ClinicalTrials.gov, number NCT02500446. Findings: Between Sept 21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or placebo group (n=19). All enrolled participants completed the study procedures and no individuals were lost to follow up. All participants were on suppressive ART with 12{\%} receiving protease inhibitors and the others non-nucleoside reverse transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7 was −0·17 (IQR −0·90 to 0·90) in the dolutegravir group and −0·26 (−1·00 to 1·17) in the placebo group (p=0·17). The addition of dolutegravir to pre-existing ART regimens was safe and there were no treatment discontinuations or treatment-related serious adverse events. Interpretation: Our findings show that in HIV-infected individuals on modern suppressive ART regimens, residual replication is rare, if at all present, and was not recorded in blood after dolutegravir intensification. Because tissue biopsies were not done we cannot exclude the possibility of residual virus replication in tissue. Strategies other than ART alone are needed to eliminate HIV persistence on treatment. Funding: ViiV Healthcare.",
author = "Rasmussen, {Thomas A.} and McMahon, {James H.} and Chang, {J. Judy} and Jennifer Audsley and Ajantha Rhodes and Surekha Tennakoon and Ashanti Dantanarayana and Tim Spelman and Tina Schmidt and Kent, {Stephen J.} and Vincent Morcilla and Sarah Palmer and Elliott, {Julian H.} and Lewin, {Sharon R.}",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/S2352-3018(18)30040-7",
language = "English",
volume = "5",
pages = "e221--e230",
journal = "Lancet HIV",
number = "5",

}

RIS

TY - JOUR

T1 - The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals

T2 - a randomised, placebo-controlled, double-blind trial

AU - Rasmussen, Thomas A.

AU - McMahon, James H.

AU - Chang, J. Judy

AU - Audsley, Jennifer

AU - Rhodes, Ajantha

AU - Tennakoon, Surekha

AU - Dantanarayana, Ashanti

AU - Spelman, Tim

AU - Schmidt, Tina

AU - Kent, Stephen J.

AU - Morcilla, Vincent

AU - Palmer, Sarah

AU - Elliott, Julian H.

AU - Lewin, Sharon R.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. Methods: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per mL at screening and two CD4 counts higher than 350 cells per μL in the previous 24 months including screening. Participants were randomly assigned (1:1) to receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The primary outcome was the change from baseline in frequency of 2-long terminal repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is registered with ClinicalTrials.gov, number NCT02500446. Findings: Between Sept 21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or placebo group (n=19). All enrolled participants completed the study procedures and no individuals were lost to follow up. All participants were on suppressive ART with 12% receiving protease inhibitors and the others non-nucleoside reverse transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7 was −0·17 (IQR −0·90 to 0·90) in the dolutegravir group and −0·26 (−1·00 to 1·17) in the placebo group (p=0·17). The addition of dolutegravir to pre-existing ART regimens was safe and there were no treatment discontinuations or treatment-related serious adverse events. Interpretation: Our findings show that in HIV-infected individuals on modern suppressive ART regimens, residual replication is rare, if at all present, and was not recorded in blood after dolutegravir intensification. Because tissue biopsies were not done we cannot exclude the possibility of residual virus replication in tissue. Strategies other than ART alone are needed to eliminate HIV persistence on treatment. Funding: ViiV Healthcare.

AB - Background: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment. Methods: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia. Eligible participants had fewer than 50 copies per mL HIV-1 plasma RNA for more than 3 years and fewer than 20 copies per mL at screening and two CD4 counts higher than 350 cells per μL in the previous 24 months including screening. Participants were randomly assigned (1:1) to receive 50 mg oral dolutegravir or placebo once a day for 56 days in addition to background ART. Follow-up was done at days 1, 3, 7, 14, 28, 56, and 84. The primary outcome was the change from baseline in frequency of 2-long terminal repeat (2-LTR) circles in peripheral blood CD4 cells at day 7. This trial is registered with ClinicalTrials.gov, number NCT02500446. Findings: Between Sept 21, 2015, and Sept 19, 2016, 46 individuals were screened for inclusion. 40 were eligible for inclusion and were randomly assigned to the dolutegravir (n=21) or placebo group (n=19). All enrolled participants completed the study procedures and no individuals were lost to follow up. All participants were on suppressive ART with 12% receiving protease inhibitors and the others non-nucleoside reverse transcriptase inhibitors. Median 2-LTR circles fold-change from baseline to day 7 was −0·17 (IQR −0·90 to 0·90) in the dolutegravir group and −0·26 (−1·00 to 1·17) in the placebo group (p=0·17). The addition of dolutegravir to pre-existing ART regimens was safe and there were no treatment discontinuations or treatment-related serious adverse events. Interpretation: Our findings show that in HIV-infected individuals on modern suppressive ART regimens, residual replication is rare, if at all present, and was not recorded in blood after dolutegravir intensification. Because tissue biopsies were not done we cannot exclude the possibility of residual virus replication in tissue. Strategies other than ART alone are needed to eliminate HIV persistence on treatment. Funding: ViiV Healthcare.

UR - http://www.scopus.com/inward/record.url?scp=85044931673&partnerID=8YFLogxK

U2 - 10.1016/S2352-3018(18)30040-7

DO - 10.1016/S2352-3018(18)30040-7

M3 - Journal article

VL - 5

SP - e221-e230

JO - Lancet HIV

JF - Lancet HIV

IS - 5

ER -