PMID- 33273328
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 133
IP  - 23
DP  - 2020 Dec 5
TI  - Safety and efficacy of allogeneic natural killer cell immunotherapy on human 
      immunodeficiency virus type 1 immunological non-responders: a brief report.
PG  - 2803-2807
LID - 10.1097/CM9.0000000000001189 [doi]
AB  - BACKGROUND: Allogeneic natural killer (NK) cell immunotherapy is recognized as a 
      promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery 
      among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. 
      This study aimed to investigate the safety and effectiveness of allogeneic NK 
      cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving 
      antiretroviral therapy (ART). METHODS: From February to April 2018, a 
      prospective, randomized, controlled, open-label clinical trial, which enrolled 20 
      HIV-1 INRs following specific inclusion criteria, was conducted at Nankai 
      University Second People's Hospital. Participants were randomly allocated (simple 
      randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or 
      the control (ART) group (n = 10). The allogenic highly activated NK cells from 
      killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw 
      mismatched healthy donor were prepared (10 cells in each injection) and 
      intravenously infused to each recruited patient of NK+ART group in three courses. 
      Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests 
      (count of blood cells, biochemistry panel) and symptoms at baseline and at month 
      1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy 
      of the therapy. Comparisons were between the seven time-points of both groups 
      using repeated measurement analysis of variance (ANOVA) test. Generalized 
      estimating equations (GEE) model was performed to evaluate the overall effect of 
      the NK+ART group vs. the ART group. RESULTS: From baseline to 24 months, we noted 
      a mean CD4 count augmentation (139 to 243 cells/muL) in the NK + ART group and 
      (144 to 176 cells/muL) in the ART group (difference, 67; 95% CI, 10 to 124; 
      P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level 
      (beta = 54.59, P = 0.006) and CD8 level (beta = 322.47, P = 0.010) on average among the 
      six measurements compared with the ART group. Only two (2/10, 20%) participants 
      in the NK+ART group developed a transient mild fever after the first course. 
      CONCLUSIONS: This preliminary study informs that HIV-1 INRs, allogenic NK cells 
      immunotherapy is safe and could significantly improve CD4 recovery but not 
      CD4/CD8 ratio. The practical effects, however, need long-term follow-up 
      observations. Further study on the potential underlying mechanism is warranted. 
      REGISTRATION INFO:: www.chictr.org.cn/showproj.aspx?proj=34912 (No. 
      ChiCTR1900020634).
FAU - Xia, Huan
AU  - Xia H
AD  - Department of Infectious Diseases, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
FAU - Wang, Yin
AU  - Wang Y
AD  - Department of Infectious Diseases, Public Health Clinical Center of Chengdu, 
      Chengdu, Sichuan 610066, China.
FAU - Sun, Hua-Li
AU  - Sun HL
AD  - Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong 266000, China.
FAU - Gao, Li-Ying
AU  - Gao LY
AD  - Department of Infectious Diseases, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
FAU - Cao, Yu
AU  - Cao Y
AD  - Tianjin Institute of Hepatology, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
FAU - Zaongo, Silvere D
AU  - Zaongo SD
AD  - Department of Infectious Diseases, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
FAU - Zeng, Rong-Nan
AU  - Zeng RN
AD  - Tianjin Institute of Hepatology, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
FAU - Wu, Hao
AU  - Wu H
AD  - Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical 
      University, Beijing 100069, China.
FAU - Zhang, Ming-Jie
AU  - Zhang MJ
AD  - HANK Bioengineering Co., Ltd., Shenzhen, Guangdong 518000, China.
FAU - Ma, Ping
AU  - Ma P
AD  - Department of Infectious Diseases, Nankai University Second People's Hospital, 
      Tianjin 300192, China.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
SB  - IM
MH  - CD4 Lymphocyte Count
MH  - *HIV Infections/therapy
MH  - *HIV-1
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Immunotherapy
MH  - Killer Cells, Natural
MH  - Prospective Studies
MH  - Viral Load
PMC - PMC7717728
COIS- None.
EDAT- 2020/12/05 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/12/05
CRDT- 2020/12/04 05:38
PHST- 2020/12/04 05:38 [entrez]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/12/05 00:00 [pmc-release]
AID - 00029330-202012050-00006 [pii]
AID - CMJ-2020-2180 [pii]
AID - 10.1097/CM9.0000000000001189 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2020 Dec 5;133(23):2803-2807. doi: 
      10.1097/CM9.0000000000001189.