{"id":2472,"date":"1998-12-31T00:00:56","date_gmt":"1998-12-30T17:00:56","guid":{"rendered":"https:\/\/www.hivnat.org\/en\/?p=2472"},"modified":"2022-03-30T10:11:30","modified_gmt":"2022-03-30T03:11:30","slug":"a-randomized-open-label-phase-ii-study-of-subcutaneous-interleukin-2-proleukinr-plus-antiretroviral-therapy-art-versus-art-alone-in-patients-with-hiv-infection-and-cd4-lymphocyte-count-greater","status":"publish","type":"post","link":"https:\/\/www.hivnat.org\/en\/studies\/2472\/","title":{"rendered":"A randomized, open-label, phase 2 study of subcutaneous interleukin-2 (ProleukinR) plus antiretroviral therapy (ART) versus ART alone in patients with HIV infection and CD4+ lymphocyte count greater than 350 cells\/mm3"},"content":{"rendered":"\n<p><strong>Background:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Interleukin-2 (IL-2) is an immuno-stimulatory protein, which is central to the appropriate responsiveness of the immune system challenged by invading pathogens<\/li><li>Previous studies have shown that the administration of IL-2 in cycles of 5 days every 8 weeks resulted in significant and sustained increases in CD4+ cell counts (Kovacs et al, 1995a) <\/li><\/ul>\n\n\n\n<p><strong>Objectives:<\/strong> To evaluate the safety. tolerance and efficacy (as measured by changes in CD+ cell counts) of IL-2 in combination with antiretroviral therapy<\/p>\n\n\n\n<p><strong>Study Design<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>The comparative study enrolled 72 patients who were randomized to one of the following two arm<ul><li>Antiretroviral double nucleoside combination therapy alone (n = 36)<\/li><li>Antiretroviral double nucleoside combination therapy plus IL-2 q12h for 5 days every 8 weeks (n = 36)<\/li><\/ul><\/li><li>The first group of 12 patients received IL-2 at a dose of 1.5 MID q12h for 5 days. This was increased to 4.5 MIU and then 7.5 MIU when at least 9 patients from each group completed the first cycle without significant toxicity<\/li><li>Patients initiated with 1.5 or 4.5 MIU and completing 3 cycles were escalated by 3 MIU\/cycle to maximum of 7.5 MIU<\/li><li>Monitoring at days 1, 2, 3, 4, 5 and 29 of each cycle and also at day 8 in the first cycle for patients receiving IL-2<\/li><li>Patients on ART alone monitored at weeks 8, 16 and 24 <\/li><\/ul>\n\n\n\n<p><strong>Result and Discussion:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>67% of participants were female<\/li><li>Mean baseline CD4+ cell count was 520<\/li><li>Adverse events reported include fever, myalgia, malaise and edema<\/li><li>There were infrequent in the 1.5 MIU group, but more common at 4.5 and  7.5 MIU<\/li><li>No serious adverse events related to study medication were reported<\/li><li>At week 16, median CD4+ counts were 1370, 954, 714 and 598 cells\/ml in the IL-2 groups 7.5, 4.5 and 1.5 MIU and the ARV alone group, respectively (p &lt; 0.05)<\/li><li>Analyses of viral load, T cell subsets and apoptosis are ongoing<\/li><li>Despite the smaller body weight of participants in this study compared to those in other studies with IL-2, these preliminary result suggest that the maximum tolerated and effective dose of subcutaneous IL-2 among Thai patients is 7.5 MIU twice dialy<\/li><li>Therefore, it is appropriate to consider this as the initial dose in the proposed phase three study <\/li><\/ul>\n\n\n\n<p><strong>Project no.:<\/strong> HIV-NAT 004 Extension Phase<\/p>\n\n\n\n<p>All patients who complete at least 6 months therapy as part of the above protocol with acceptable compliance are eligible for this extension phase<\/p>\n\n\n\n<p><strong>Study Design<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Patients randomized to subcutaneous IL-2 in protocol HIV-NAT 004 may continue to receive cycles of IL-2 for this extended one-year of follow-up<\/li><li>Administration of IL-2 is on an individual basis according to following guildlines:<ul><li>Objective of ongoing IL-2 therapy is to maintain the individual&#8217;s CD4+ cell count at a level at least twice baseline, or 1000 cell\/mm<sup>3<\/sup> or greater<\/li><li>Cycles of IL-2 therapy continue every 8 weeks for those individuals whose CD4+ cell count is below these levels<\/li><li>If CD4 cell count is above these desired levels, the next protocol mandated cycle of treatment may be postponed until the CD4 cell count falls below these levels<\/li><li>Follow-up visits are every 4 months (or any interval deemed appropriate for routine patient care)<\/li><\/ul><\/li><li>Gradual, stepped dose escalation to a maximum of 7.5 MIU is permitted for those receiving IL-2 at doses of 1.5 MIU and 4.5 MIU<\/li><li>Dose reduction is permitted in ceses of intolerance <\/li><\/ul>\n\n\n\n<p><strong>Results: <\/strong>Interim data analysis pending<\/p>\n","protected":false},"excerpt":{"rendered":"<p>\t\t\t\tInterleukin-2 (IL-2) is an immuno-stimulatory protein, which is central to the appropriate responsiveness of the immune system challenged by invading pathogens\t\t<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[24],"tags":[],"class_list":["post-2472","post","type-post","status-publish","format-standard","hentry","category-studies"],"_links":{"self":[{"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/posts\/2472","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/comments?post=2472"}],"version-history":[{"count":2,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/posts\/2472\/revisions"}],"predecessor-version":[{"id":3360,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/posts\/2472\/revisions\/3360"}],"wp:attachment":[{"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/media?parent=2472"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/categories?post=2472"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.hivnat.org\/en\/wp-json\/wp\/v2\/tags?post=2472"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}