Back to resultsEarly cART and cART in Combination With Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in The Treatment of Acute HIV-1 Infected Adults
Primary Purpose
Acute HIV Infection
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
cART(TDF/AZT+3TC+LPV/r)
CTL infusion
Sponsored by
About this trial
This is an interventional treatment trial for Acute HIV Infection focused on measuring HIV Infections, Acquired Immunodeficiency Syndrome, Immunologic Deficiency Syndromes, Immune System Diseases, Lentivirus Infections, Retroviridae Infections, Virus Diseases, RNA Virus Infections, Sexually Transmitted Diseases, Viral, Slow Virus Diseases, Therapeutic Uses, Pharmacologic Actions, Antiretroviral therapy, Early therapy
Eligibility Criteria
Inclusion Criteria:
Diagnosis of acute HIV infection (meets one of following criteria)
- Negative for anti-HIV test formerly, but with an anti-HIV serological conversion within 6 months
- Detection of plasma HIV RNA by RT-PCR in the absence of HIV antibody
- Low-level of anti-HIV for BED HIV-1 capture enzyme immuno assay (BED-CEIA), optical density (OD)<0.6, only for B subtype)
- Uncertain for an anti-HIV test, with an increasing anti-HIV level for repeated test within two weeks
- A patient with a report of recent risk behavior in association with symptoms and signs of the acute retroviral syndrome, as well as a positive for HIV antigen detection and less than 4 bands in a Western blot assay
- Ability, willingness to give informed consent
- Able, willing to adhere to therapy and adherent to ART
- Able, willing to comply with time requirements for study visits and evaluations
Exclusion Criteria:
- Chronic HIV - 1 infection
- Any evidence of an active AIDS-defining opportunistic infection
- Screening detects the following results:HGB<90g/L、WBC< 2 x 10E9/L、PLT< 75 x 10E9/L、hemodiastase>2 x ULN、Scr>1.5 x ULN、ALT/AST/ALP> 3 xULN、TbiL>2 xULN、CK>2 xULN、CCr<60ml/min
- A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points
- History of chronic kidney disease
- History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
- History of Severe peptic ulcer
- History of alcoholism and drug abuse
- Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to screening
- Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period
- Have contraindications to cART
- Other condition that does not fit to participate in this study
Sites / Locations
- Beijing You'an Hospital, Capital Medical University
- National Center for STD and AIDS Control and Prevention, Chinese Center for Disease Control and Prevention
- The First Affiliated Hospital of Guangxi Medical University
- China Medical University
- Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical Universit
- Shandong Center for Disease Control and Prevention
- Zhejiang University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
cART(TDF/AZT+3TC+LPV/r)
CTL infusion
Arm Description
cART(TDF/AZT+3TC+LPV/r)
cART plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion
Outcomes
Primary Outcome Measures
Change from baseline in HIV DNA quantification at the interruption of cART
HIV DNA detection includes total HIV DNA, integrated HIV DNA , 2-long terminal repeat （LTR） HIV DNA in resting CD4+T cell subsets.
Number of patients who achieve virological remission
Virological remission is defined as undetectable of plasma HIV RNA for 24 weeks after the interruption of cART.
Secondary Outcome Measures
Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events
Number of patients who need to initiate late treatment
Late treatment is defined cART should be administered according to local HIV treatment guidelines.
Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)
HIV-1 specific CD4+ and CD8+ T cell responses at week 120
Full Information
NCT ID
NCT02231281
First Posted
August 26, 2014
Last Updated
April 24, 2018
Sponsor
Yongtao Sun, MD, PhD
Collaborators
Tang-Du Hospital, National Center for AIDS/STD Control and Prevention, China CDC, Beijing YouAn Hospital, China Medical University, China, Shandong Province Centers for Disease Control and Prevention, Zhejiang University, First Affiliated Hospital of Guangxi Medical University
1. Study Identification
Unique Protocol Identification Number
NCT02231281
Brief Title
Early cART and cART in Combination With Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in The Treatment of Acute HIV-1 Infected Adults
Official Title
A Randomized, Open-label Trial to Compare the Efficacy and Safety of Early Initiation of cART With or Without Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in Treatment-Naïve Acute HIV-1 Infected Adults
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (Actual)
Primary Completion Date
August 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yongtao Sun, MD, PhD
Collaborators
Tang-Du Hospital, National Center for AIDS/STD Control and Prevention, China CDC, Beijing YouAn Hospital, China Medical University, China, Shandong Province Centers for Disease Control and Prevention, Zhejiang University, First Affiliated Hospital of Guangxi Medical University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the ability of the early initiation of cART or cART in combination with autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion to achieve a post-treatment control among treatment-naïve acute HIV-infected adults.
Detailed Description
Although combined antiretroviral therapy (cART) can suppress HIV-1 replication to a very low level in the blood, but it cannot eliminate latent viral reservoirs, and need lifelong adherence to expensive regimens that have potential side effects. Increasing evidence indicates that early antiretroviral therapy for recently HIV-infected patients results in slower progression of HIV disease and represent a unique opportunity to interfere with either the quantities or qualities of persistent reservoirs of replication-competent virus. However, the time course before the interruption of cART is unclear. This study will compare the virological and immunological outcomes and HIV latency of recently infected adults who receive cART or cART in combination with autologous HIV-1 CTL infusion for different periods.
The study will last 120 weeks. Participants will be randomly assigned to either the cART or the cART plus autologous HIV-1 CTL infusion arm of one of three cohorts. The three cohorts will differ in the period of cART given. Cohort 1, Cohort 2 or Cohort 3 will receive cART (Zidovudine (AZT)/Tenofovir disoproxil fumarate (TDF) +Lamivudine (3TC） + Lopinavir / Ritonavir （LPV/r)） for 48, 72 or 96 weeks, respectively. After 48, 72 or 96 weeks, cART will be interrupted respectively. Study visits will occur at study entry, Week 4 and 12, and every 12 weeks thereafter through treatment interruption, then every 4 weeks through 12 weeks later, then every 12 weeks through Week 120. At each study visit, a physical exam, blood collection, and completion of an adherence questionnaire will occur. Clinical, virological, and immunological evaluations and HIV latency examination will be performed at most study visit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute HIV Infection
Keywords
HIV Infections, Acquired Immunodeficiency Syndrome, Immunologic Deficiency Syndromes, Immune System Diseases, Lentivirus Infections, Retroviridae Infections, Virus Diseases, RNA Virus Infections, Sexually Transmitted Diseases, Viral, Slow Virus Diseases, Therapeutic Uses, Pharmacologic Actions, Antiretroviral therapy, Early therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
65 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
cART(TDF/AZT+3TC+LPV/r)
Arm Type
Experimental
Arm Description
cART(TDF/AZT+3TC+LPV/r)
Arm Title
CTL infusion
Arm Type
Experimental
Arm Description
cART plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion
Intervention Type
Drug
Intervention Name(s)
cART(TDF/AZT+3TC+LPV/r)
Other Intervention Name(s)
Tenofovir Disoproxil Fumarate, Zidovudine, Lamivudine, Lopinavir/ritonavir (Kaletra)
Intervention Description
Standard antiretroviral therapy for HIV infection
Intervention Type
Procedure
Intervention Name(s)
CTL infusion
Intervention Description
cART(TDF/AZT+3TC+LPV/r) plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion
Primary Outcome Measure Information:
Title
Change from baseline in HIV DNA quantification at the interruption of cART
Description
HIV DNA detection includes total HIV DNA, integrated HIV DNA , 2-long terminal repeat （LTR） HIV DNA in resting CD4+T cell subsets.
Time Frame
48 weeks for Cohort 1, 72 weeks for Cohort 2, 96 weeks for Cohort 3
Title
Number of patients who achieve virological remission
Description
Virological remission is defined as undetectable of plasma HIV RNA for 24 weeks after the interruption of cART.
Time Frame
72 weeks for Cohort 1, 96 weeks for Cohort 2, 120 weeks for Cohort 3
Secondary Outcome Measure Information:
Title
Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events
Time Frame
120 weeks
Title
Number of patients who need to initiate late treatment
Description
Late treatment is defined cART should be administered according to local HIV treatment guidelines.
Time Frame
120 weeks
Title
Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)
Time Frame
120 weeks
Title
HIV-1 specific CD4+ and CD8+ T cell responses at week 120
Time Frame
120 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of acute HIV infection (meets one of following criteria)
Negative for anti-HIV test formerly, but with an anti-HIV serological conversion within 6 months
Detection of plasma HIV RNA by RT-PCR in the absence of HIV antibody
Low-level of anti-HIV for BED HIV-1 capture enzyme immuno assay (BED-CEIA), optical density (OD)<0.6, only for B subtype)
Uncertain for an anti-HIV test, with an increasing anti-HIV level for repeated test within two weeks
A patient with a report of recent risk behavior in association with symptoms and signs of the acute retroviral syndrome, as well as a positive for HIV antigen detection and less than 4 bands in a Western blot assay
Ability, willingness to give informed consent
Able, willing to adhere to therapy and adherent to ART
Able, willing to comply with time requirements for study visits and evaluations
Exclusion Criteria:
Chronic HIV - 1 infection
Any evidence of an active AIDS-defining opportunistic infection
Screening detects the following results:HGB<90g/L、WBC< 2 x 10E9/L、PLT< 75 x 10E9/L、hemodiastase>2 x ULN、Scr>1.5 x ULN、ALT/AST/ALP> 3 xULN、TbiL>2 xULN、CK>2 xULN、CCr<60ml/min
A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points
History of chronic kidney disease
History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
History of Severe peptic ulcer
History of alcoholism and drug abuse
Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to screening
Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period
Have contraindications to cART
Other condition that does not fit to participate in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yongtao Sun, M.D., Ph.D.
Organizational Affiliation
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing You'an Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
National Center for STD and AIDS Control and Prevention, Chinese Center for Disease Control and Prevention
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Facility Name
Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical Universit
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710038
Country
China
Facility Name
Shandong Center for Disease Control and Prevention
City
Jinan
State/Province
Shandong
Country
China
Facility Name
Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China
12. IPD Sharing Statement
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Early cART and cART in Combination With Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in The Treatment of Acute HIV-1 Infected Adults
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