Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults

September 11, 2018 updated by: AIDS Clinical Trials Group

International Trial of Modified Directly Observed Therapy Versus Self-Administered Therapy for Participants With First Virologic Failure on a Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Regimen

Highly active antiretroviral therapy (HAART) has led to better health and survival rates among people with HIV/AIDS. The purpose of this study was to measure the effect of trained partner supervision when taking medication versus self-administered therapy in HIV infected participants. These participants have had their first virologic failure on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen and were starting a protease inhibitor (PI)-based HAART regimen at study entry.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Poor adherence to HAART is usually associated with resistant virus. Poor adherence to HAART can have serious consequences, including limited treatment options for HIV infected individuals if they become infected with resistant HIV. The purpose of this study was to examine the effectiveness of modified directly observed therapy (mDOT) and compare it with the effectiveness of self-administered therapy (non-mDOT) in HIV infected individuals with first virologic failure on an NNRTI-based HAART regimen who were starting a PI-based HAART regimen at study entry.

mDOT was defined in this study as the daily observation of lopinavir/ritonavir (LPV/r) being taken on a regular basis. Observation consisted of an mDOT partner being present at the time the study participant took the observed dose. Half of the participants in this study were required to choose an mDOT partner to supervise adherence for the first 24 weeks of the study. Each mDOT partner completed the study-administered mDOT training program and was required to record all observed doses in an mDOT diary log. All participants and partners received health education through the study. Adherence was measured using Medication Event Monitoring System (MEMS) caps and self-report questionnaires.

This study lasted 52 weeks. Per protocol, participants were to be stratified according to their screening viral load and the proposed study treatment. The study treatment each participant received was based on their treatment history. At entry, participants were to start one of the two PI-based HAART regimens, either FTC/Tenofovir Disoproxil Fumarate (TDF) 200/300 mg once daily (QD) and Lopinavir/Ritonavir (LPV/RTV) 400/100 mg twice a day (BID) or TDF 300 mg QD and zidovudine (ZDV) 300 mg BID and LPV/RTV 400/100 mg BID. mDOT was used for the first 24 weeks of the study, followed by self-administration of study medications from week 25 to week 52. ZDV was not provided by the study. All enrolled participants except one who did not start study regimen initiated FTC/TDF and LPV/rtv after randomization. No participants started ZDV containing regimen on study. Thus, participants in this study were stratified by screening HIV-1 RNA only.

There were eight visits during the study. Medical and medication history, blood collection, and clinical assessment were required at all visits. A quality of life questionnaire and an adherence tools assessment were collected at most visits. For the mDOT arm, medication diary logs and mDOT partner monitoring were reviewed at most visits. An mDOT exit questionnaire and exit interview were required at the end of the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
529

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Botswana
      • Gaborone, Botswana
        • Gaborone Prevention/Treatment Trials CRS
  • Brazil
      • Rio de Janeiro, Brazil, 21045
        • Instituto de Pesquisa Clinica Evandro Chagas (12101)
  • Haiti
    • Port-au-Prince
      • Bicentenaire, Port-au-Prince, Haiti, HT-6110
        • Les Centres GHESKIO CRS
  • Peru
      • Lima, Peru, 18
        • Barranco CRS
    • Lima
      • San Miguel, Lima, Peru
        • San Miguel CRS
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa
        • Wits HIV CRS
  • Uganda
      • Kampala, Uganda
        • JCRC CRS
  • Zambia
      • Lusaka, Zambia
        • Kalingalinga Clinic CRS
  • Zimbabwe
      • Harare, Zimbabwe
        • UZ-Parirenyatwa CRS

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria for Participants:

  • HIV infected
  • Have experienced or currently experiencing first baseline virologic failure on first NNRTI-based HAART regimen with no history of virologic failure on another regimen OR discontinued first NNRTI-based HAART regimen without the recommendations of clinicians and currently experiencing virologic failure with no history of virologic failure on another regimen. More information on this criterion can be found in the protocol.
  • Confirmed virologic failure within 45 days of study entry
  • Receiving one of the following NNRTI-based regimens for at least 16 weeks prior to study entry: ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP or d4T+3TC+EFV
  • Able to identify a close friend, relative, or spouse who is willing to serve as a partner
  • Intend to stay in current geographical area of residence for the duration of the study
  • Agree to use LPV/rtv with MEMS caps and take the tablets out of the container only at dosing
  • Willing to use acceptable forms of contraception
  • Ability and willingness of participant or legal guardian/representative to give written informed consent.
  • Required laboratory values obtained within 45 days prior to study entry.
  • Negative serum or urine pregnancy test obtained within 48 hours prior to study entry for women of reproductive potential.

Inclusion Criteria for Partners:

  • Not a participant
  • Friend, family member, or spouse who knows of the participant's HIV status. Partners do not have to live with participants.
  • Willing to attend a 1- to 2-hour taped training session prior to study entry
  • Willing to attend study visits with participant at study screening; entry; and Weeks 4, 8, 12, 24, and 52
  • Willing to directly observe participant taking at least one dose of LPV/rtv for at least 5 days per week for 24 weeks after stratification of participant
  • Willing to act as a positive support for participant
  • Willing to notify clinical staff of participant's nonadherence to study assigned regimen
  • Willing to notify clinical staff if they are unable to provide mDOT for 2 weeks or more
  • Willing to complete medication diary logs
  • Willing to complete exit interview
  • Agree to have their training session taped (if required).
  • For mDOT arm, willing to discuss and decide with participants whether to continue mDOT after Week 24
  • At least 18 years old
  • Understand that participants have agreed to use LPV/RTV with MEMS caps and take the tablets out of the container only at dosing
  • Ability and willingness to give written informed consent.
  • No intention to relocate away from current geographical area of residence for the duration of study participation.

Exclusion Criteria for Participants:

  • Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days of study entry
  • Prior treatment with any PI
  • Previously diagnosed cancer other than basal cell carcinoma and cutaneous Kaposi's sarcoma
  • Use of rifampin or rifabutin within 45 days of study entry or plan use of rifampin or rifabutin
  • Requirement for taking any medications that are prohibited by this study. More information on this criterion can be found in the protocol.
  • Known allergy to the study medications or their formulations
  • Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study
  • Acute illness requiring hospitalization within 14 days of study entry
  • Active tuberculosis (TB) infection
  • Currently incarcerated
  • Participation as a partner in this study
  • Participation with no access to telephones
  • Abnormal laboratory values
  • Pregnant, breastfeeding, or intend to become pregnant

Exclusion Criteria for Partners:

  • A participant in this study
  • Participation as a partner to any other participant
  • No access to telephones
  • Currently incarcerated

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: mDOT arm
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
Drug: Lopinavir/ritonavir
Two tablets (200-mg lopinavir and 50 mg ritonavir in each tablet), taken orally twice daily
Other Names:
  • Kaletra
  • LPV/r
  • LPV/RTV
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
  • Truvada
  • FTC/TDF
Drug: Tenofovir disoproxil fumarate
300-mg tablet taken orally once daily
Other Names:
  • TDF
  • Viread
Drug: Zidovudine
300-mg tablet taken orally twice daily
Other Names:
  • ZDV
  • Retrovir
Drug: Emtricitabine
200-mg tablet taken orally once daily
Other Names:
  • FTC
  • Emtriva
Active Comparator: non-mDOT arm
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Drug: Lopinavir/ritonavir
Two tablets (200-mg lopinavir and 50 mg ritonavir in each tablet), taken orally twice daily
Other Names:
  • Kaletra
  • LPV/r
  • LPV/RTV
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
  • Truvada
  • FTC/TDF
Drug: Tenofovir disoproxil fumarate
300-mg tablet taken orally once daily
Other Names:
  • TDF
  • Viread
Drug: Zidovudine
300-mg tablet taken orally twice daily
Other Names:
  • ZDV
  • Retrovir
Drug: Emtricitabine
200-mg tablet taken orally once daily
Other Names:
  • FTC
  • Emtriva

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Confirmed Virologic Failure at or Prior to Week 48
Time Frame: At or prior to Week 48
Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) <1 log10 copies/mL below the baseline level and >400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) >400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤50 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 48 was reported.
At or prior to Week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Confirmed Virologic Failure at or Prior to Week 24
Time Frame: At or prior to Week 24
Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) <1 log10 copies/mL below the baseline level and >400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) >400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤30 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 24 was reported.
At or prior to Week 24
CD4 Count at Follow-up Visits
Time Frame: At Weeks 4, 12, 24, 36, and 48
CD4 cell count (median, inter-quartile range)
At Weeks 4, 12, 24, 36, and 48
CD8 Count at Follow-up Visits
Time Frame: At week 4, 12, 24, 36, and 48
CD8 cell count (median, inter-quartile range)
At week 4, 12, 24, 36, and 48
Time to First Grade 3 or 4 Lab Event
Time Frame: 52 weeks since randomization
5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event
52 weeks since randomization
Time to First Grade 3 or 4 Sign or Symptom
Time Frame: 52 weeks since randomization
5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom
52 weeks since randomization
Time to First Grade 3 or 4 Lab or Sign/Symptom Event
Time Frame: 52 weeks since randomization
5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab or sign/ symptom event
52 weeks since randomization
Adherence to Second Line HAART Regimen
Time Frame: At weeks 4, 8, 12, 24, 36, 48 and 52
Number of participants with self-reported 100% adherence over the week prior to study visit
At weeks 4, 8, 12, 24, 36, 48 and 52

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AIDS Clinical Trials Group

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Robert Gross, MD, MSCE, University of Pennsylvania
  • Study Chair: Alberto La Rosa, MD, Asociación Civil Impacta Salud y Educación, Peru

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

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 Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 21, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 6, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACTG A5234
  • 1U01AI068636 (U.S. NIH Grant/Contract)

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.

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