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

NCT02231281 | Unknown Phase 3 DMC

• 1 other identifier: 2014ZX10001002-001
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  48 weeks for Cohort 1, 72 weeks for Cohort 2, 96 weeks for Cohort 3

• 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.

  72 weeks for Cohort 1, 96 weeks for Cohort 2, 120 weeks for Cohort 3

Secondary Outcomes (4)

• Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events

  120 weeks

• Number of patients who need to initiate late treatment

  120 weeks

• Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)

  120 weeks

• HIV-1 specific CD4+ and CD8+ T cell responses at week 120

  120 weeks

Study Arms (2)

cART(TDF/AZT+3TC+LPV/r)

EXPERIMENTAL

cART(TDF/AZT+3TC+LPV/r)

Drug: cART(TDF/AZT+3TC+LPV/r)

CTL infusion

EXPERIMENTAL

cART plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion

Drug: cART(TDF/AZT+3TC+LPV/r); Procedure: CTL infusion

Interventions

cART(TDF/AZT+3TC+LPV/r) DRUG

Standard antiretroviral therapy for HIV infection

Also known as: Tenofovir Disoproxil Fumarate, Zidovudine, Lamivudine, Lopinavir/ritonavir (Kaletra)

CTL infusion; cART(TDF/AZT+3TC+LPV/r)

CTL infusion PROCEDURE

cART(TDF/AZT+3TC+LPV/r) plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion

CTL infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yongtao Sun, MD, PhD: lead
• Tang-Du Hospital: collaborator
• National Center for AIDS/STD Control and Prevention, China CDC: collaborator
• Beijing YouAn Hospital: collaborator
• China Medical University, China: collaborator
• Shandong Province Centers for Disease Control and Prevention: collaborator
• Zhejiang University: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator

Study Sites (7)

Beijing You'an Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

National Center for STD and AIDS Control and Prevention, Chinese Center for Disease Control and Prevention

Beijing, Beijing Municipality, China

Location

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

China Medical University

Shenyang, Liaoning, China

Location

Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical Universit

Xi'an, Shaanxi, 710038, China

Location

Shandong Center for Disease Control and Prevention

Jinan, Shandong, China

Location

Zhejiang University

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

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

Interventions

Tenofovir; Zidovudine; Lamivudine; Lopinavir; Ritonavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidinones; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Yongtao Sun, M.D., Ph.D.

  Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Infectious Diseases

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: September 4, 2014
• Study Start: August 1, 2014
• Primary Completion: August 1, 2018
• Study Completion: December 1, 2018
• Last Updated: April 26, 2018

Record last verified: 2018-04

Locations

CN (7)