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

Yongtao Sun, MD, PhD

Status and phase: Unknown; Phase 3

Conditions: Acute HIV Infection

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02231281

2014ZX10001002-001 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 65 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of acute HIV infection (meets one of following criteria)

   1. Negative for anti-HIV test formerly, but with an anti-HIV serological conversion within 6 months
   2. Detection of plasma HIV RNA by RT-PCR in the absence of HIV antibody
   3. Low-level of anti-HIV for BED HIV-1 capture enzyme immuno assay (BED-CEIA), optical density (OD)<0.6, only for B subtype)
   4. Uncertain for an anti-HIV test, with an increasing anti-HIV level for repeated test within two weeks
   5. 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

2. Ability, willingness to give informed consent

3. Able, willing to adhere to therapy and adherent to ART

4. Able, willing to comply with time requirements for study visits and evaluations

Exclusion criteria

1. Chronic HIV - 1 infection
2. Any evidence of an active AIDS-defining opportunistic infection
3. 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
4. A personal history of clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points
5. History of chronic kidney disease
6. History of malignancy or transplantation, including skin cancers or Kaposi sarcoma
7. History of Severe peptic ulcer
8. History of alcoholism and drug abuse
9. Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents within 28 days prior to screening
10. 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
11. Have contraindications to cART
12. Other condition that does not fit to participate in this study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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65 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

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

CTL infusion

Experimental group

Description:

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

Treatment:

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

Procedure: CTL infusion

Sponsors of this trial

Lead Sponsor

Yongtao Sun, MD, PhD

Collaborating Sponsors

Zhejiang University

Shandong Provincial Center for Disease Control and Prevention

Capital Medical University

First Affiliated Hospital of Guangxi Medical University

Tang-Du Hospital

National Center for AIDS/STD Control and Prevention, China CDC

China Medical University, China