Anti-HIV Medications and Structured Treatment Interruptions for People Recently Infected With HIV

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00084032
First received: June 4, 2004
Last updated: October 26, 2012
Last verified: October 2012
  Purpose

People recently infected with HIV who are treated with anti-HIV medications may develop strong immune system responses to HIV and may be able to control the virus without continuing to take these medications. The purpose of this study is to see if giving anti-HIV medications to people soon after they have been infected with HIV can help them control HIV. The study will also see if the immune system can control the amount of HIV virus in the blood (viral load) even after a person has stopped taking the medications. The study will evaluate three different schedules of stopping and starting anti-HIV medications to see which schedule is best able to boost a patient's immune system to control HIV viral load.

Hypothesis: Combination therapy started in primary HIV infection, in conjunction with structured treatment interruptions, will result in greater control of viremia off treatment than induction therapy alone.


Condition Intervention
HIV Infections
Behavioral: Structured treatment interruption
Drug: Antiretroviral regimen

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter Trial to Determine Whether Induction Therapy Followed by Treatment Interruption is Superior to Induction Therapy Alone in the Treatment of Primary HIV Infection (PHI): The Structured Treatment Interruption (STI) Study

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Difference in mean HIV viral load between arms [ Time Frame: At Week 80 ] [ Designated as safety issue: No ]

Enrollment: 0
Arms Assigned Interventions
Experimental: 1
In Step 1, participants will receive ARV therapy for 24 weeks. Upon entering Step 2, participants will continue taking ARV therapy for 16 weeks and then stop ARVs for 64 weeks.
Behavioral: Structured treatment interruption
Treatment interruption schedule is dependent on the Arm in which participants are enrolled in Step 2
Drug: Antiretroviral regimen
Participants will take any combination of FDA-approved ARV medications prescribed by their physician
Experimental: 2
In Step 1, participants will receive ARV therapy for 24 weeks. Upon entering Step 2, participants will stop ARVs for 4 weeks, take ARVs for 8 weeks, stop ARVs for 4 weeks, take ARVs for 8 weeks, and then stop ARVs for 56 weeks.
Behavioral: Structured treatment interruption
Treatment interruption schedule is dependent on the Arm in which participants are enrolled in Step 2
Drug: Antiretroviral regimen
Participants will take any combination of FDA-approved ARV medications prescribed by their physician

Detailed Description:

Initiation of treatment during acute HIV infection seems to result in greater suppression of viral replication than noted during chronic infection and better recovery of certain CD4 subpopulations. However, it is difficult for patients treated during acute infection to maintain long-term continuous antiretroviral (ARV) treatment because of difficulty adhering to complicated medication regimens, drug-related toxicities, and cost of medications. Acutely infected patients who have undergone early initiation of treatment followed by structured treatment interruptions (STIs) appear to have lower off-treatment viral loads than historical controls. This study will evaluate whether effective ARV treatment during acute and early HIV infection followed by STI will result in lower viral setpoints than would otherwise be expected.

This trial will have 2 steps and will last for a maximum of 104 weeks. Participants will either enter Step 1 and continue on to Step 2 or enter Step 2 directly. During Step 1, participants with acute or early HIV infection will be given 24 weeks of ARV therapy. Participants may take any combination of FDA-approved ARV medications that they and their doctors select. Participants will have study visits at study entry and Weeks 1, 4, 8, and 20. After 24 weeks on Step 1, participants may enroll in Step 2.

Participants in Step 1 and people with early or acute HIV infection who began ARV treatment within 21 days of diagnosis and have had no more than 1 year of treatment may enroll in Step 2. During Step 2, participants will be randomly assigned to one of two study arms:

  • Arm 1: Participants will continue taking ARV therapy for 16 weeks and then stop ARVs for 64 weeks.
  • Arm 2: Participants will stop ARVs for 4 weeks, take ARVs for 8 weeks, stop ARVs for 4 weeks, take ARVs for 8 weeks, and then stop ARVs for 56 weeks.

Participants in both study arms will restart ARVs regardless of STI duration if their viral load is above 50,000 copies/ml, they progress to CDC category C disease, or their CD4 count falls below 350 cells/mm3 or declines more than 50% from the last on-treatment CD4 level.

Step 2 will last 80 weeks. For the first year, participants will have study visits every 1 to 4 weeks, depending on whether they are taking ARVs. During the second year, participants will have study visits every 8 weeks. Study visits will include a brief medical history, blood and pregnancy tests, and voluntary behavioral questionnaires.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Note: Step 2, Arm 3 has been eliminated as of 12/13/04.

Inclusion Criteria for Step 1:

  • Acute or early HIV infection as defined by the study
  • Agrees to use acceptable methods of contraception
  • Agrees to begin antiretroviral treatment regimen within 21 days of diagnosis and no more than 3 days after study entry

Exclusion Criteria for Step 1:

  • Unwilling to follow random assignment in Step 2
  • Abnormal laboratory result within 21 days prior to study entry, unless abnormality is considered part of acute HIV infection
  • Have taken antiretroviral drugs other than for postexposure prophylaxis (PEP). Patients who have undergone up to 30 days of previous PEP treatment are not excluded.
  • Pregnancy or breastfeeding
  • Previous participation in an HIV vaccine trial
  • Previous use of experimental therapeutic immunizations or cytokine infusions

Inclusion Criteria for Participants Enrolling Directly into Step 2:

  • Viral load of less than 400 copies/ml
  • Enrolled in the AIEDRP CORE01 study, with stored blood samples obtained within 21 days prior to starting treatment on CORE01
  • Currently receiving antiretroviral treatment regimen, with no interruptions for more than 7 consecutive days since the beginning of treatment
  • Antiretroviral treatment was started within 21 days after HIV diagnosis
  • Agrees to use acceptable methods of contraception

Exclusion Criteria for Step 2:

  • Unwilling to follow random assignment to study arms and follow scheduled treatment interruptions
  • More than 52 weeks of ARV treatment since diagnosis of acute/early HIV infection prior to entering Step 2
  • CD4 count less than 350 cells/mm3 within 28 days of entry into Step 2
  • AIDS-defining illness
  • Pregnant or breastfeeding
  • Previous participation in an HIV vaccine trial
  • Previous use of experimental therapeutic immunizations or cytokine infusions
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084032

Sponsors and Collaborators
Investigators
Study Chair: Eric Rosenberg, MD Massachusetts General Hospital
Study Chair: Don Smith, MB, ChB, MD University of New South Wales, Australia
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00084032     History of Changes
Other Study ID Numbers: AIEDRP AIN502
Study First Received: June 4, 2004
Last Updated: October 26, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acute Infection
Treatment Interruption
Treatment Naive
Primary HIV Infection
PHI

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on August 01, 2014