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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00608569
First received: January 21, 2008
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
HIV Infections
Drug: Lopinavir/ritonavir
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Tenofovir disoproxil fumarate
Drug: Zidovudine
Drug: Emtricitabine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Confirmed Virologic Failure at or Prior to Week 48 [ Time Frame: At or prior to Week 48 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Confirmed Virologic Failure at or Prior to Week 24 [ Time Frame: At or prior to Week 24 ] [ Designated as safety issue: Yes ]
    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.

  • CD4 Count at Follow-up Visits [ Time Frame: At Weeks 4, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    CD4 cell count (median, inter-quartile range)

  • CD8 Count at Follow-up Visits [ Time Frame: At week 4, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
    CD8 cell count (median, inter-quartile range)

  • Time to First Grade 3 or 4 Lab Event [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
    5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event

  • Time to First Grade 3 or 4 Sign or Symptom [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
    5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom

  • Time to First Grade 3 or 4 Lab or Sign/Symptom Event [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
    5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab or sign/ symptom event

  • Adherence to Second Line HAART Regimen [ Time Frame: At weeks 4, 8, 12, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
    Number of participants with self-reported 100% adherence over the week prior to study visit


Enrollment: 529
Study Start Date: March 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • LPV/RTV
  • LPV/r
  • Kaletra
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
  • FTC/TDF
  • Truvada
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:
  • LPV/RTV
  • LPV/r
  • Kaletra
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
  • FTC/TDF
  • Truvada
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

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.

  Eligibility

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

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
  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: NCT00608569

Locations
Botswana
Gaborone Prevention/Treatment Trials CRS
Gaborone, Botswana
Brazil
Instituto de Pesquisa Clinica Evandro Chagas (12101)
Rio de Janeiro, Brazil, 21045
Haiti
Les Centres GHESKIO CRS
Bicentenaire, Port-au-Prince, Haiti, HT-6110
Peru
San Miguel CRS
San Miguel, Lima, Peru
Barranco CRS
Lima, Peru, 18
South Africa
Wits HIV CRS
Johannesburg, Gauteng, South Africa
Uganda
JCRC CRS
Kampala, Uganda
Zambia
Kalingalinga Clinic CRS
Lusaka, Zambia
Zimbabwe
UZ-Parirenyatwa CRS
Harare, Zimbabwe
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: Robert Gross, MD, MSCE University of Pennsylvania
Study Chair: Alberto La Rosa, MD Asociación Civil Impacta Salud y Educación, Peru
  More Information

Additional Information:
Publications:
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00608569     History of Changes
Other Study ID Numbers: ACTG A5234, 1U01AI068636
Study First Received: January 21, 2008
Results First Received: September 5, 2013
Last Updated: November 14, 2013
Health Authority: United States: Federal Government

Keywords provided by AIDS Clinical Trials Group:
Drug Therapy, Combination
HIV Non-Nucleoside Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Viral Load
Virologic Failure

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
Ritonavir
Lopinavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014