Clinical trial NCT02231281: 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
Overall status: UNKNOWN
Phase: PHASE3
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
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
Collaborators: name: Tang-Du Hospital
name: National Center for AIDS/STD Control and Prevention, China CDC
name: Beijing YouAn Hospital
name: China Medical University, China
name: Shandong Province Centers for Disease Control and Prevention
name: Zhejiang University
name: First Affiliated Hospital of Guangxi Medical University
First posted: 2014-09-04
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in HIV DNA quantification at the interruption of cART
timeFrame: 48 weeks for Cohort 1, 72 weeks for Cohort 2, 96 weeks for Cohort 3
measure: Number of patients who achieve virological remission
timeFrame: 72 weeks for Cohort 1, 96 weeks for Cohort 2, 120 weeks for Cohort 3
Secondary outcomes:
measure: Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events
timeFrame: 120 weeks
measure: Number of patients who need to initiate late treatment
timeFrame: 120 weeks
measure: Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)
timeFrame: 120 weeks
measure: HIV-1 specific CD4+ and CD8+ T cell responses at week 120
timeFrame: 120 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing You'an Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: National Center for STD and AIDS Control and Prevention, Chinese Center for Disease Control and Prevention
state: Beijing
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shenyang
country: China
facility: China Medical University
state: Liaoning
city: Xi'an
country: China
facility: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical Universit
state: Shaanxi
city: Jinan
country: China
facility: Shandong Center for Disease Control and Prevention
state: Shandong
city: Hangzhou
country: China
facility: Zhejiang University
state: Zhejiang
Study officials:
affiliation: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
name: Yongtao Sun, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: