Efficacy and safety of Mianyi granules(免疫Ⅱ颗粒) for reversal of immune nonresponse following antiretroviral therapy of human immunodeficiency virus-1:a randomized,double-blind,multi-center,placebo-controlled trial

OBJECTIVE:To investigate whether Mianyi granules(免疫Ⅱ颗粒)are effective and safe in reversing immune nonresponse following antiretroviral therapy(ART)in individuals with human immunodeficiency virus(HIV)infection.METHODS:Randomized,double-blind,multi-center,placebo-controlled trial(factorial design)of daily oral Mianyi granules versus placebo for 72 weeks.A total of 361 HIV-positive individuals receiving ART at five ClassⅢGradeⅠhospitals in China between September 2013 and January 2016 completed the study.The primary endpoints were frequencies of CD3+,CD4+,CD8+,and CD45 RA+cells at seven timepoints over the 72 weeks.Secondary endpoints included viral loads,clinical symptoms,and quality of life at 72 weeks.RESULTS:A total of 400 participants were enrolled in the study and randomized,of whom 361 completed the study:189 individuals(140 men and 49 women)in the Mianyi granule group and 172 individuals(135 men and 37 women)in the placebo group.In the intent-to-treat population,CD4+T cell counts increased from(193±71)cells/mm^(3)at baseline to(288±131)cells/mm^(3)posttreatment in the Mianyi granule group and from(200±75)cells/mm^(3)at baseline to(264±124)cells/mm^(3)posttreatment in the placebo group.Patients treated with Mianyi granule had higher increases in CD4+T cell counts than those treated with placebo(P=0.045).Reversal of immune nonresponse was defined as a CD4+T cell increase of more than 100 cells/mm^(3).After treatment for 72 weeks,Mianyi granule was effective in reversing immune nonresponse in a higher proportion of individuals(20.2%)compared with placebo(9.7%).CD45 RA+cell counts increased from(34±32)cell/mm^(3)at baseline to(51±61)cells/mm^(3)post-treatment in the Mianyi granule group and from(37±33)cells/mm^(3)at baseline to(48±37)cells/mm^(3)post-treatment in the placebo group.Mianyi granules were more effective than placebo in increasing CD45 RA+cell counts.CONCLUSIONS:In ART-treated HIV-positive adults with immune nonresponse,treatment with Mianyi granules for 72 weeks was safe and significantly increased CD4+and CD45 RA+cell counts,thereby promoting immune reconstitution.