Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults
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Purpose
Highly active antiretroviral therapy (HAART) has led to better health and survival rates among people with HIV/AIDS. The purpose of this study is to measure the effect of trained partner supervision when taking medication versus self-administered therapy in HIV infected participants. These participants will have had their first virologic failure on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen and will be starting a protease inhibitor (PI)-based HAART regimen.
| Condition | Intervention |
|---|---|
|
HIV Infections |
Drug: Lopinavir/ritonavir Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Tenofovir disoproxil fumarate Drug: Zidovudine |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Confirmed virologic failure [ Time Frame: At or prior to Week 48 ] [ Designated as safety issue: Yes ]
- Confirmed virologic failure [ Time Frame: At or prior to Week 24 ] [ Designated as safety issue: Yes ]
- CD4 count [ Time Frame: At Weeks 4, 12, 14, 36, and 48 ] [ Designated as safety issue: Yes ]
- Occurence of adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Grade 2, 3, or 4 signs and symptoms; Grade 3 or 4 laboratory test abnormal values; new diagnoses [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Acceptability and feasibility of mDot [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Adherence and resistance to second line HAART regimen [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
| Enrollment: | 529 |
| Study Start Date: | March 2009 |
| Estimated Study Completion Date: | November 2012 |
| Estimated Primary Completion Date: | November 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Oral FTC/TDF and LPV/r for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
|
Drug: Lopinavir/ritonavir
200-mg lopinavir and 50 mg ritonavir in each tablet, taken orally twice daily
Other Names:
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
|
|
Experimental: 2
Oral TDF, ZDV, and LPV/r for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
|
Drug: Lopinavir/ritonavir
200-mg lopinavir and 50 mg ritonavir in each tablet, taken orally twice daily
Other Names:
Drug: Tenofovir disoproxil fumarate
200-mg tablet taken orally once daily
Other Names:
Drug: Zidovudine
300-mg tablet taken orally twice daily
Other Names:
|
|
Experimental: 3
Self-administration of oral FTC/TDF and LPV/r for 52 weeks
|
Drug: Lopinavir/ritonavir
200-mg lopinavir and 50 mg ritonavir in each tablet, taken orally twice daily
Other Names:
Drug: Emtricitabine/Tenofovir disoproxil fumarate
200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily
Other Names:
|
|
Experimental: 4
Self-administered oral TDF, ZDV, and LPV/r for 52 weeks
|
Drug: Lopinavir/ritonavir
200-mg lopinavir and 50 mg ritonavir in each tablet, taken orally twice daily
Other Names:
Drug: Tenofovir disoproxil fumarate
200-mg tablet taken orally once daily
Other Names:
Drug: Zidovudine
300-mg tablet taken orally twice daily
Other Names:
|
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 is to examine the effectiveness of modified directly observed therapy (mDOT) and compare it with the effectiveness of self-administered therapy in HIV infected individuals with first virologic failure on an NNRTI-based HAART regimen who are starting a PI-based HAART regimen.
mDOT is defined in this study as the daily observation of lopinavir/ritonavir (LPV/r) being taken on a regular basis. Observation consists of an mDOT partner being present at the time the study participant takes the observed dose. Half of the participants in this study will be required to choose an mDOT partner to supervise adherence for the first 28 weeks of the study. Each mDOT partner will complete the study-administered mDOT training program and must record all observed doses in an mDOT diary log. All participants and partners will receive health education through the study. Adherence will be measured using Medication Event Monitoring System (MEMS) caps and self-report questionnaires.
This study will last approximately 52 weeks. Participants will be stratified according to their viral load into one of four arms. The arm in which each participant is placed by the clinician is based on the treatment history of the participant. Participants in Arms 1 and 3 will receive emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and lopinavir/ritonavir (LPV/r) for the duration of the study. Participants in Arms 2 and 4 will receive LPV/r, TDF, and zidovudine (ZDF) for the duration of the study. mDOT will be used for the first 24 weeks of the study. For the remaining 28 weeks, participants in Arms 1 and 2 will use self-administration without mDOT. Participants in Arms 3 and 4 will self-administer study medications without mDOT for all 52 weeks. ZDV will not be provided by the study.
There will be eight visits during the study. Medical and medication history, blood collection, and adherence monitoring will occur at all visits. A quality of life questionnaire and an adherence tools assessment will occur at most visits. For Arms 1 and 2, medication diary logs and mDOT partner monitoring will be reviewed at most visits. An mDOT exit questionnaire and exit interview will occur at the end of the study for each partner.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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, and NVP; ZDV, 3TC, and EFV; d4T, 3TC, and NVP; OR d4T, 3TC, and EFV
- Able to identify a close friend, relative, or spouse who is willing to serve as a partner (for Arms 1 and 2 only)
- Intend to stay in current geographical area of residence for the duration of the study
- Agree to use LPV/r with MEMS caps and take the tablets out of the container only at dosing
- Willing to use acceptable forms of contraception
Inclusion Criteria for Partners:
- 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 observe participant taking at least one dose of LPV/r 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
- In Arms 3 and 4, 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
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
- Require certain 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 abuse 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
- 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| Botswana | |
| Gaborone Prevention/Treatment Trials CRS | |
| Gaborone, Botswana | |
| Brazil | |
| Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Fundacao Oswaldo Cruz | |
| Rio de Janero, Brazil, 21045 | |
| Haiti | |
| Les Centres GHESKIO CRS | |
| Bicentenaire, Port-au-Prince, Haiti, HT-6110 | |
| Peru | |
| San Miguel CRS | |
| San Miguel, Lima, Peru | |
| Asociacion Civil Impacta Salud y Educacion - Miraflores, 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 | |
| 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 |
| Last Updated: | November 16, 2012 |
| 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 Zidovudine Reverse Transcriptase Inhibitors Tenofovir Tenofovir disoproxil |
Ritonavir Lopinavir Emtricitabine HIV Protease Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents Protease Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013