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

October 26, 2012 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference in mean HIV viral load between arms
Time Frame: At Week 80
At Week 80

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Eric Rosenberg, MD, Massachusetts General Hospital
  • Study Chair: Don Smith, MB, ChB, MD, University of New South Wales, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

June 4, 2004

First Submitted That Met QC Criteria

June 4, 2004

First Posted (Estimate)

June 7, 2004

Study Record Updates

Last Update Posted (Estimate)

October 29, 2012

Last Update Submitted That Met QC Criteria

October 26, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIEDRP AIN502

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on Structured treatment interruption

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe