Daily Low-Dose Subcutaneous Interleukin-2 Added To Single- or Dual-Nucleoside Therapy in HIV Infection Does Not Protect Against CD4+ T-Cell Decline or Improve Other Indices of Immune Function: Results of a Randomized Controlled Clinical Trial (ACTG 248)

Vogler, Mary; Teppler, Hedy; Gelman, Rebecca; Valentine, Fred; Lederman, Michael M.; Pomerantz, Roger J.; Pollard, Richard B.; Cherng, Deborah Weng; Gonzalez, Charles J.; Squires, Kathleen; Frank, Ian; Mildvan, Donna; Mahon, Laura F.; Schock, Barbara

doi:10.1097/00126334-200405010-00005

Cited by 16 publications

(24 citation statements)

References 19 publications

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“…Eleven trials were conducted in academic centres in the USA (Abrams 2002; Davey 2000; Dybul 2002; de Boer 2003; Abrams 2009a; Abrams 2009b; Kovacs 1996; Lalezari 2000; Mitsuyasu 2007; Tavel 2003; Vogler 2004). The other 14 included trials were conducted in Argentina (Losso 2000), France (Katlama 2002; Levy 1999; Levy 2003), Italy (Amendola 2000; Caggiari 2001; Marchetti 2002; Marchetti 2004; Tambussi 2001), Australia (Carr 1998; Kelleher 1998), Germany (Hengge 1998; Stellbrink 2002), and Thailand (Ruxrungtham 2000).…”

Section: Resultsmentioning

confidence: 99%

“…Some trials had three trial arms that compared different routes of administration, including subcutaneous versus intravenous administration with the control group (ART alone) (Carr 1998; Mitsuyasu 2007; Tambussi 2001). Other included trials had three trial arms that compared IL-2, a control group, and different modified forms of IL-2, such as polyethylene glycol (PEG) modified IL-2 (Carr 1998; Kelleher 1998; Levy 1999), and granulocyte stimulating factor-modified IL-2 (Amendola 2000), and prednisone-modified IL-2 (Vogler 2004). …”

Section: Resultsmentioning

confidence: 99%

“…We considered the following trials to have a low risk of attrition bias with low or minimal loss to follow-up: Abrams 2002; Abrams 2009a; Abrams 2009b; Carr 1998; Davey 2000; de Boer 2003; Hengge 1998; Katlama 2002; Kelleher 1998; Kovacs 1996; Levy 1999; Levy 2003; Losso 2000; Marchetti 2002; Marchetti 2004; Stellbrink 2002; Tambussi 2001; and Vogler 2004. There was high risk of attrition bias in Lalezari 2000 and Mitsuyasu 2007.…”

Section: Resultsmentioning

confidence: 99%

“…Eight trials reported on all-cause mortality (Abrams 2002; Abrams 2009a; Abrams 2009b; Kovacs 1996; Levy 1999; Losso 2000; Mitsuyasu 2007; Vogler 2004). Trials reported mortality at six months (Vogler 2004), 12 months (Abrams 2002), 13 months (Levy 1999), 14 months (Kovacs 1996), 20 months (Mitsuyasu 2007), and seven years (Abrams 2009b; Abrams 2009a).…”

Section: Resultsmentioning

confidence: 99%

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Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults

Onwumeh

Okwundu

Kredo

2017

Cochrane Database of Systematic Reviews

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Background Human immunodeficiency virus (HIV) continues to be a leading cause of morbidity and mortality, particularly in sub‐Saharan Africa. Although antiretroviral drugs have helped to improve the quality of life and life expectancy of HIV‐positive individuals, there is still a need to explore other interventions that will help to further reduce the disease burden. One potential strategy is the use of interleukin‐2 (IL‐2) in combination with antiretroviral therapy (ART). IL‐2 is a cytokine that regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system. Objectives To assess the effects of interleukin‐2 (IL‐2) as an adjunct to antiretroviral therapy for HIV‐positive adults. Search methods We searched the following sources up to 26 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; the Web of Science; LILACS; the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP); and ClinicalTrials.gov. We also checked conference abstracts, contacted experts and relevant organizations in the field, and checked the reference list of all studies identified by the above methods for any other potentially eligible studies. Selection criteria Randomized controlled trials (RCTs) that evaluated the effects of IL‐2 as an adjunct to ART in reducing the morbidity and mortality in HIV‐positive adults. Data collection and analysis Two review authors independently screened records and selected trials that met the inclusion criteria, extracted data, and assessed the risk of bias in the included trials. Where possible, we compared the effects of interventions using risk ratios (RR), and presented them with 95% confidence intervals (CI). We assessed the overall certainty of the evidence using the GRADE approach. Main results Following a comprehensive literature search up to 26 May 2016, we identified 25 eligible trials. The interventions involved the use of IL‐2 in combination with ART compared with ART alone. There was no difference in mortality apparent between the IL‐2 group and the ART alone group (RR 0.97, 95% CI 0.80 to 1.17; 6 trials, 6565 participants, high certainty evidence ). Seventeen of 21 trials reported an increase in the CD4 cell count with the use of IL‐2 compared to control using different measures (21 trials, 7600 participants). Overall, there was little or no difference in the proportion of participants with a viral load of less than 50 cells/mL or less than 500 cells/mL by the end of the trials (RR 0.97, 95% CI 0.81 to 1.15; 5 trials, 805 participants, high certainty evidence ) and (RR 0.96, 95% CI 0.82 to 1.12; 4 trials, 5929 participants, high certainty evidence ) respectively. Overall there may be little or no diff...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults

Onwumeh

Okwundu

Kredo

2017

Cochrane Database of Systematic Reviews

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“…The different randomized CD4 cell count-guided (referred to hereafter as CD4-guided) studies in VL-suppressed patients are summarized in Table 1. Because of space constraints, studies that are non-randomized or use non-standard HAART are not described [12,13,[18][19][20][21].…”

Section: Scheduled Treatment Interruption Studies In Chronic Hiv Infementioning

confidence: 99%

Intermittent therapy for the treatment of chronic HIV infection

Ananworanich

Hirschel

2007

Aids

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Safety of low-dose subcutaneous recombinant interleukin-2: systematic review and meta-analysis of randomized controlled trials

Mahmoudpour

Jankowski

Valerio

et al. 2019

Sci Rep

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Standard-dose intravenous recombinant interleukin-2 (rIL-2) is indicated for the treatment of some subtypes of cancer; however, severe adverse events, including venous thromboembolism (VTE), may complicate its administration. Low-dose subcutaneous rIL-2 is being studied for the management of immune-mediated diseases, since it can modulate the immunological response by specifically targeting T regulatory (T reg ) cells; importantly, it is supposed to cause fewer or no complications. In this systematic review and meta-analysis of phase II-III randomized controlled trials (RCTs), we investigated the safety of low-dose (<6 Million International Unit [MIU]/day) and ultra-low-dose (≤1 MIU/day) rIL-2 for severe adverse events (grade III-V) with a focus on VTE. Data of 1,321 patients from 24 RCTs were analysed: 661 patients were randomized to the rIL-2 arm (on top of standard of care) and 660 patients to standard of care alone or placebo. Two studies reported higher rates of thrombocytopenia in the low-dose rIL-2 arm. Ultra-low-dose rIL-2 was reported to be well tolerated in 6 studies with a negligible rate of severe adverse events. Symptomatic VTE events were not reported in any of the study arms (absolute risk difference 0% [95%CI −0.1%; +0.1%]). Our results may facilitate the study and introduction in clinical practice of low-dose rIL-2 for potentially new indications.

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Daily Low-Dose Subcutaneous Interleukin-2 Added To Single- or Dual-Nucleoside Therapy in HIV Infection Does Not Protect Against CD4+ T-Cell Decline or Improve Other Indices of Immune Function: Results of a Randomized Controlled Clinical Trial (ACTG 248)

Cited by 16 publications

References 19 publications

Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults

Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults

Intermittent therapy for the treatment of chronic HIV infection

Safety of low-dose subcutaneous recombinant interleukin-2: systematic review and meta-analysis of randomized controlled trials

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