Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study

Jorge A. Tavel; Abdel Babiker; Cate Carey; Martin Fisher; Lawrence Fox; Daniela Gey; Gustavo D. Lopardo; Juan Carlos Lopez; Norman Markowitz; David Munroe; Nick Paton; Kiat Ruxrungtham; Barbara Standridge; Deborah Wentworth; Nicole Wyman; Bitten Aagaard; Liselotte Borup; Jesper Grarup; Per Olof Jansson; Karoline Jensen; Jens Lundgren; David Mollerup; Søren Reilev; Nafisah Braimah; Janet Darbyshire; Jessica Horton; Eleanor King; Nicki Smith; Fionna Van Hooff; David A. Cooper; David Courtney-Rodgers; Sean Emery; Elizabeth Finley; Fred Gordin; Adriana Sánchez; Doug Thomas; Judith Bebchuk; Patty Bollenbeck; Eileen Denning; Alain G. DuChene; Lisa Fosdick; Merrie Harrison; Eric Krum; Gregg Larson; James D. Neaton; Ray Nelson; Kien Quan; Siu Fun L. Quan; Terri Schultz; Greg Thompson; Simon Collins; David Hans Haerry; Michael Meulbroek; Dwight Peavy; Claire Rappoport; Siegfried Schwarze; Mirta Valdez; Jo Watson; Waldo H. Belloso; Rick Davey; Daniel Duprez; Jose Maria Gatell; Jenny Hoy; Alan Lifson; Court Pederson; George Perez; Richard Price; Ronald Prineas; Frank Rhame; James H. Sampson; John Worley; John F. Modlin; Valerie Beral; Richard E. Chaisson; Thomas R. Fleming; Catherine Hill; Kyung Mann Kim; Barbara E. Murray; Billy Pick; Maxime Seligmann; Ian Weller; Mary Anne Luzar; Ana Martinez; Vanita Costas; Julie Eckstrand; Shawn Brown; Sergio H. Lupo; Marcelo H. Losso; Jonathan Anderson; John Chuah; Mark Kelly; David Orth; Marcelo J. Wolff; Stefano Rusconi; Giuseppe Tambussi; Andrzej Horban; Francisco Antunes; Kamal Mansinho; Jose Alfredo Viegas Da Conceicao Vera; Hakima Himmich; Ploenchan Chetchotisakd; Pacharee Kantipong; Chloe Orkin; Simon Portsmouth; Alan Winston; Martin J. Wiselka; Gregory M. Anstead; Roberto C. Arduino; Matthew B. Goetz; Karen Hennessey; Wafaa El-Sadr; Ann M. Labriola; Daniel E. Nixon; Maria C. Rodriguez-Barradas

doi:10.1371/journal.pone.0009334

Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study

Jorge A. Tavel, Abdel Babiker, Cate Carey, Martin Fisher, Lawrence Fox, Daniela Gey, Gustavo D. Lopardo, Juan Carlos Lopez, Norman Markowitz, David Munroe, Nick Paton, Kiat Ruxrungtham, Barbara Standridge, Deborah Wentworth, Nicole Wyman, Bitten Aagaard, Liselotte Borup, Jesper Grarup, Per Olof Jansson, Karoline JensenJens Lundgren, David Mollerup, Søren Reilev, Nafisah Braimah, Janet Darbyshire, Jessica Horton, Eleanor King, Nicki Smith, Fionna Van Hooff, David A. Cooper, David Courtney-Rodgers, Sean Emery, Elizabeth Finley, Fred Gordin, Adriana Sánchez, Doug Thomas, Judith Bebchuk, Patty Bollenbeck, Eileen Denning, Alain G. DuChene, Lisa Fosdick, Merrie Harrison, Eric Krum, Gregg Larson, James D. Neaton, Ray Nelson, Kien Quan, Siu Fun L. Quan, Terri Schultz, Greg Thompson, Simon Collins, David Hans Haerry, Michael Meulbroek, Dwight Peavy, Claire Rappoport, Siegfried Schwarze, Mirta Valdez, Jo Watson, Waldo H. Belloso, Rick Davey, Daniel Duprez, Jose Maria Gatell, Jenny Hoy, Alan Lifson, Court Pederson, George Perez, Richard Price, Ronald Prineas, Frank Rhame, James H. Sampson, John Worley, John F. Modlin, Valerie Beral, Richard E. Chaisson, Thomas R. Fleming, Catherine Hill, Kyung Mann Kim, Barbara E. Murray, Billy Pick, Maxime Seligmann, Ian Weller, Mary Anne Luzar, Ana Martinez, Vanita Costas, Julie Eckstrand, Shawn Brown, Sergio H. Lupo, Marcelo H. Losso, Jonathan Anderson, John Chuah, Mark Kelly, David Orth, Marcelo J. Wolff, Stefano Rusconi, Giuseppe Tambussi, Andrzej Horban, Francisco Antunes, Kamal Mansinho, Jose Alfredo Viegas Da Conceicao Vera, Hakima Himmich, Ploenchan Chetchotisakd, Pacharee Kantipong, Chloe Orkin, Simon Portsmouth, Alan Winston, Martin J. Wiselka, Gregory M. Anstead, Roberto C. Arduino, Matthew B. Goetz, Karen Hennessey, Wafaa El-Sadr, Ann M. Labriola, Daniel E. Nixon, Maria C. Rodriguez-Barradas

School of Medicine

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Abstract

Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4⁺ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4⁺ cells/mm³ were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 ⁺ counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4⁺ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4⁺ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4⁺ cells. Trial Registration: ClinicalTrials.gov NCT00110812.

Original language	English (US)
Article number	e9334
Journal	PloS one
Volume	5
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0009334
State	Published - Feb 23 2010

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Tavel, J. A., Babiker, A., Carey, C., Fisher, M., Fox, L., Gey, D., Lopardo, G. D., Lopez, J. C., Markowitz, N., Munroe, D., Paton, N., Ruxrungtham, K., Standridge, B., Wentworth, D., Wyman, N., Aagaard, B., Borup, L., Grarup, J., Jansson, P. O., ... Rodriguez-Barradas, M. C. (2010). Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study. PloS one, 5(2), Article e9334. https://doi.org/10.1371/journal.pone.0009334

Tavel, JA, Babiker, A, Carey, C, Fisher, M, Fox, L, Gey, D, Lopardo, GD, Lopez, JC, Markowitz, N, Munroe, D, Paton, N, Ruxrungtham, K, Standridge, B, Wentworth, D, Wyman, N, Aagaard, B, Borup, L, Grarup, J, Jansson, PO, Jensen, K, Lundgren, J, Mollerup, D, Reilev, S, Braimah, N, Darbyshire, J, Horton, J, King, E, Smith, N, Van Hooff, F, Cooper, DA, Courtney-Rodgers, D, Emery, S, Finley, E, Gordin, F, Sánchez, A, Thomas, D, Bebchuk, J, Bollenbeck, P, Denning, E, DuChene, AG, Fosdick, L, Harrison, M, Krum, E, Larson, G, Neaton, JD, Nelson, R, Quan, K, Quan, SFL, Schultz, T, Thompson, G, Collins, S, Haerry, DH, Meulbroek, M, Peavy, D, Rappoport, C, Schwarze, S, Valdez, M, Watson, J, Belloso, WH, Davey, R, Duprez, D, Gatell, JM, Hoy, J, Lifson, A, Pederson, C, Perez, G, Price, R, Prineas, R, Rhame, F, Sampson, JH, Worley, J, Modlin, JF, Beral, V, Chaisson, RE, Fleming, TR, Hill, C, Kim, KM, Murray, BE, Pick, B, Seligmann, M, Weller, I, Luzar, MA, Martinez, A, Costas, V, Eckstrand, J, Brown, S, Lupo, SH, Losso, MH, Anderson, J, Chuah, J, Kelly, M, Orth, D, Wolff, MJ, Rusconi, S, Tambussi, G, Horban, A, Antunes, F, Mansinho, K, Da Conceicao Vera, JAV, Himmich, H, Chetchotisakd, P, Kantipong, P, Orkin, C, Portsmouth, S, Winston, A, Wiselka, MJ, Anstead, GM, Arduino, RC, Goetz, MB, Hennessey, K, El-Sadr, W, Labriola, AM, Nixon, DE & Rodriguez-Barradas, MC 2010, 'Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study', PloS one, vol. 5, no. 2, e9334. https://doi.org/10.1371/journal.pone.0009334

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title = "Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study",

abstract = "Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration: ClinicalTrials.gov NCT00110812.",

author = "Tavel, {Jorge A.} and Abdel Babiker and Cate Carey and Martin Fisher and Lawrence Fox and Daniela Gey and Lopardo, {Gustavo D.} and Lopez, {Juan Carlos} and Norman Markowitz and David Munroe and Nick Paton and Kiat Ruxrungtham and Barbara Standridge and Deborah Wentworth and Nicole Wyman and Bitten Aagaard and Liselotte Borup and Jesper Grarup and Jansson, {Per Olof} and Karoline Jensen and Jens Lundgren and David Mollerup and S{\o}ren Reilev and Nafisah Braimah and Janet Darbyshire and Jessica Horton and Eleanor King and Nicki Smith and {Van Hooff}, Fionna and Cooper, {David A.} and David Courtney-Rodgers and Sean Emery and Elizabeth Finley and Fred Gordin and Adriana S{\'a}nchez and Doug Thomas and Judith Bebchuk and Patty Bollenbeck and Eileen Denning and DuChene, {Alain G.} and Lisa Fosdick and Merrie Harrison and Eric Krum and Gregg Larson and Neaton, {James D.} and Ray Nelson and Kien Quan and Quan, {Siu Fun L.} and Terri Schultz and Greg Thompson and Simon Collins and Haerry, {David Hans} and Michael Meulbroek and Dwight Peavy and Claire Rappoport and Siegfried Schwarze and Mirta Valdez and Jo Watson and Belloso, {Waldo H.} and Rick Davey and Daniel Duprez and Gatell, {Jose Maria} and Jenny Hoy and Alan Lifson and Court Pederson and George Perez and Richard Price and Ronald Prineas and Frank Rhame and Sampson, {James H.} and John Worley and Modlin, {John F.} and Valerie Beral and Chaisson, {Richard E.} and Fleming, {Thomas R.} and Catherine Hill and Kim, {Kyung Mann} and Murray, {Barbara E.} and Billy Pick and Maxime Seligmann and Ian Weller and Luzar, {Mary Anne} and Ana Martinez and Vanita Costas and Julie Eckstrand and Shawn Brown and Lupo, {Sergio H.} and Losso, {Marcelo H.} and Jonathan Anderson and John Chuah and Mark Kelly and David Orth and Wolff, {Marcelo J.} and Stefano Rusconi and Giuseppe Tambussi and Andrzej Horban and Francisco Antunes and Kamal Mansinho and {Da Conceicao Vera}, {Jose Alfredo Viegas} and Hakima Himmich and Ploenchan Chetchotisakd and Pacharee Kantipong and Chloe Orkin and Simon Portsmouth and Alan Winston and Wiselka, {Martin J.} and Anstead, {Gregory M.} and Arduino, {Roberto C.} and Goetz, {Matthew B.} and Karen Hennessey and Wafaa El-Sadr and Labriola, {Ann M.} and Nixon, {Daniel E.} and Rodriguez-Barradas, {Maria C.}",

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doi = "10.1371/journal.pone.0009334",

language = "English (US)",

volume = "5",

journal = "PloS one",

issn = "1932-6203",

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T1 - Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection

T2 - The STALWART study

AU - Tavel, Jorge A.

AU - Babiker, Abdel

AU - Carey, Cate

AU - Fisher, Martin

AU - Fox, Lawrence

AU - Gey, Daniela

AU - Lopardo, Gustavo D.

AU - Lopez, Juan Carlos

AU - Markowitz, Norman

AU - Munroe, David

AU - Paton, Nick

AU - Ruxrungtham, Kiat

AU - Standridge, Barbara

AU - Wentworth, Deborah

AU - Wyman, Nicole

AU - Aagaard, Bitten

AU - Borup, Liselotte

AU - Grarup, Jesper

AU - Jansson, Per Olof

AU - Jensen, Karoline

AU - Lundgren, Jens

AU - Mollerup, David

AU - Reilev, Søren

AU - Braimah, Nafisah

AU - Darbyshire, Janet

AU - Horton, Jessica

AU - King, Eleanor

AU - Smith, Nicki

AU - Van Hooff, Fionna

AU - Cooper, David A.

AU - Courtney-Rodgers, David

AU - Emery, Sean

AU - Finley, Elizabeth

AU - Gordin, Fred

AU - Sánchez, Adriana

AU - Thomas, Doug

AU - Bebchuk, Judith

AU - Bollenbeck, Patty

AU - Denning, Eileen

AU - DuChene, Alain G.

AU - Fosdick, Lisa

AU - Harrison, Merrie

AU - Krum, Eric

AU - Larson, Gregg

AU - Neaton, James D.

AU - Nelson, Ray

AU - Quan, Kien

AU - Quan, Siu Fun L.

AU - Schultz, Terri

AU - Thompson, Greg

AU - Collins, Simon

AU - Haerry, David Hans

AU - Meulbroek, Michael

AU - Peavy, Dwight

AU - Rappoport, Claire

AU - Schwarze, Siegfried

AU - Valdez, Mirta

AU - Watson, Jo

AU - Belloso, Waldo H.

AU - Davey, Rick

AU - Duprez, Daniel

AU - Gatell, Jose Maria

AU - Hoy, Jenny

AU - Lifson, Alan

AU - Pederson, Court

AU - Perez, George

AU - Price, Richard

AU - Prineas, Ronald

AU - Rhame, Frank

AU - Sampson, James H.

AU - Worley, John

AU - Modlin, John F.

AU - Beral, Valerie

AU - Chaisson, Richard E.

AU - Fleming, Thomas R.

AU - Hill, Catherine

AU - Kim, Kyung Mann

AU - Murray, Barbara E.

AU - Pick, Billy

AU - Seligmann, Maxime

AU - Weller, Ian

AU - Luzar, Mary Anne

AU - Martinez, Ana

AU - Costas, Vanita

AU - Eckstrand, Julie

AU - Brown, Shawn

AU - Lupo, Sergio H.

AU - Losso, Marcelo H.

AU - Anderson, Jonathan

AU - Chuah, John

AU - Kelly, Mark

AU - Orth, David

AU - Wolff, Marcelo J.

AU - Rusconi, Stefano

AU - Tambussi, Giuseppe

AU - Horban, Andrzej

AU - Antunes, Francisco

AU - Mansinho, Kamal

AU - Da Conceicao Vera, Jose Alfredo Viegas

AU - Himmich, Hakima

AU - Chetchotisakd, Ploenchan

AU - Kantipong, Pacharee

AU - Orkin, Chloe

AU - Portsmouth, Simon

AU - Winston, Alan

AU - Wiselka, Martin J.

AU - Anstead, Gregory M.

AU - Arduino, Roberto C.

AU - Goetz, Matthew B.

AU - Hennessey, Karen

AU - El-Sadr, Wafaa

AU - Labriola, Ann M.

AU - Nixon, Daniel E.

AU - Rodriguez-Barradas, Maria C.

PY - 2010/2/23

Y1 - 2010/2/23

N2 - Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration: ClinicalTrials.gov NCT00110812.

AB - Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration: ClinicalTrials.gov NCT00110812.

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DO - 10.1371/journal.pone.0009334

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VL - 5

JO - PloS one

JF - PloS one

IS - 2

M1 - e9334

ER -

Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study

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