A Study to Compare Anti-HIV Drugs Given Twice a Day or Once a Day, With or Without Direct Observation

NCT ID: NCT00036452

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 402 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2006-01-31

Brief Summary

Anti-HIV drug therapy works best when the drugs are taken exactly as prescribed by a doctor. Because anti-HIV therapy often involves multiple drugs, some people have difficulty taking them all correctly. The easier it is to take anti-HIV drugs, the more likely people will take them as prescribed and get the best results. This study will see if people are more successful in taking anti-HIV drugs once a day or twice a day. It also will determine if having a health care professional oversee each weekday dose helps people control their HIV infection. The study will compare taking a three-drug combination twice a day versus taking a three-drug combination just once a day. The study will also compare patients taking the drugs on their own to patients taking the drugs in the presence of a clinical worker. Viral load (amount of HIV in the blood) and drug side effects will be measured.

Detailed Description

While many factors contribute to the success or failure of antiretroviral therapy for HIV, among the most important are factors that influence adherence to a treatment regimen, such as duration of therapy, dosing frequency, pill burden, side effects, and patient behaviors. Inconsistent adherence or nonadherence to antiretroviral therapy can result in suboptimal drug exposure. Suboptimal drug exposure can, in turn, impact short- and long-term patient outcomes by increasing the likelihood of drug resistant HIV mutants and subsequent virologic and clinical failure. It is therefore essential to design treatment regimens that promote long-term adherence to potent antiretroviral therapy. This study will evaluate the relative contribution of reduced-frequency dosing and directly observed therapy on the magnitude and durability of virologic suppression in patients treated with potent antiretroviral therapy.

Patients will be randomly assigned to one of three study arms. Arms A, B, and C receive the same daily dosage of lopinavir/ritonavir (LPV/r), emtricitabine (FTC), and stavudine extended release (d4T XR) or tenofovir DF (TDF). In Arm A, drugs are self-administered for 48 weeks; LPV/r is taken twice daily and FTC and d4T XR or TDF once daily. In Arm B, all drugs are self-administered once daily for 48 weeks. In Arm C, drugs are taken once a day under directly observed therapy during Weeks 0-24, and then by self-administration during Weeks 25-48. Adherence to the regimen is measured using an electronic drug monitoring system. Viral load, CD4 and CD8 T cell responses, population pharmacokinetics, and quality of life indicators are measured throughout the study. The tolerability and safety of the treatment regimens are also monitored.

Conditions

HIV Infections

Keywords

Lopinavir; HIV-1; Drug Administration Schedule; Stavudine; HIV Protease Inhibitors; Ritonavir; Reverse Transcriptase Inhibitors; Self Care; Viral Load; Emtricitabine; Directly Observed Therapy; Tenofovir Disoproxil Fumarate; Treatment Naive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

lopinavir/ritonavir

Intervention Type: DRUG

emtricitabine

Intervention Type: DRUG

stavudine

Intervention Type: DRUG

tenofovir DF

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• HIV infection
• Age 13 years or older and have written consent of guardian if under 18
• Weigh at least 88 pounds
• Viral load of 2000 copies/ml or more within 90 days before study entry
• Have not taken anti-HIV drugs for more than 7 days
• Agree to use acceptable methods of contraception during the study and for 1 month after stopping the study drugs

Exclusion Criteria

• Pregnant or breastfeeding
• In jail
• Sensitive or allergic to any part of the study drugs
• Treated with acute systemic therapy for a serious infection or other serious medical illness within 7 days prior to study entry, unless the participant has completed 7 days of therapy and is clinically stable
• Recent serious illness, including pancreatitis or peripheral neuropathy
• Alcohol or illicit drug abuse
• Taken any of the following within 14 days before study entry: investigational drugs, anti-HIV vaccines, drugs that may cause pancreatitis or peripheral neuropathy, or drugs that are associated with CYP3A
• Treated for cancer (not including minimal Kaposi's sarcoma) within 30 days before study entry
• History of mental illness that might interfere with the study

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donna Mildvan, MD

Role: STUDY_CHAIR

Beth Israel Medical Center

Charles Flexner, MD

Role: STUDY_CHAIR

Johns Hopkins University Hospital

Locations

USC CRS

Los Angeles, California, United States

Univ. of California Davis Med. Ctr., ACTU

Sacramento, California, United States

Ucsd, Avrc Crs

San Diego, California, United States

University of Colorado Hospital CRS

Aurora, Colorado, United States

Univ. of Miami AIDS CRS

Miami, Florida, United States

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

IHV Baltimore Treatment CRS

Baltimore, Maryland, United States

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

SSTAR, Family Healthcare Ctr.

Fall River, Massachusetts, United States

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Beth Israel Med. Ctr., ACTU

New York, New York, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Univ. of Rochester ACTG CRS

Rochester, New York, United States

AIDS Care CRS

Rochester, New York, United States

McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit

Rochester, New York, United States

Unc Aids Crs

Chapel Hill, North Carolina, United States

Regional Center for Infectious Disease, Wendover Medical Center CRS

Greensboro, North Carolina, United States

Wake County Health and Human Services CRS

Raleigh, North Carolina, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

MetroHealth CRS

Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Pitt CRS

Pittsburgh, Pennsylvania, United States

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States

University of Washington AIDS CRS

Seattle, Washington, United States

Puerto Rico-AIDS CRS

San Juan, , Puerto Rico

Wits HIV CRS

Johannesburg, Gauteng, South Africa

Countries

United States; Puerto Rico; South Africa

References

Liu H, Golin CE, Miller LG, Hays RD, Beck CK, Sanandaji S, Christian J, Maldonado T, Duran D, Kaplan AH, Wenger NS. A comparison study of multiple measures of adherence to HIV protease inhibitors. Ann Intern Med. 2001 May 15;134(10):968-77. doi: 10.7326/0003-4819-134-10-200105150-00011.

Reference Type: BACKGROUND

PMID: 11352698 (View on PubMed)

Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, Wagener MM, Singh N. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000 Jul 4;133(1):21-30. doi: 10.7326/0003-4819-133-1-200007040-00004.

Reference Type: BACKGROUND

PMID: 10877736 (View on PubMed)

Volmink J, Matchaba P, Garner P. Directly observed therapy and treatment adherence. Lancet. 2000 Apr 15;355(9212):1345-50. doi: 10.1016/S0140-6736(00)02124-3.

Reference Type: BACKGROUND

PMID: 10776760 (View on PubMed)

Bangsberg DR, Mundy LM, Tulsky JP. Expanding directly observed therapy: tuberculosis to human immunodeficiency virus. Am J Med. 2001 Jun 1;110(8):664-6. doi: 10.1016/s0002-9343(01)00729-x. No abstract available.

Reference Type: BACKGROUND

PMID: 11382379 (View on PubMed)

Kirkland LR, Fischl MA, Tashima KT, Paar D, Gensler T, Graham NM, Gao H, Rosenzweig JR, McClernon DR, Pittman G, Hessenthaler SM, Hernandez JE; NZTA4007 Study Team. Response to lamivudine-zidovudine plus abacavir twice daily in antiretroviral-naive, incarcerated patients with HIV infection taking directly observed treatment. Clin Infect Dis. 2002 Feb 15;34(4):511-8. doi: 10.1086/338400. Epub 2002 Jan 4.

Reference Type: BACKGROUND

PMID: 11797179 (View on PubMed)

Gross R, Tierney C, Andrade A, Lalama C, Rosenkranz S, Eshleman SH, Flanigan T, Santana J, Salomon N, Reisler R, Wiggins I, Hogg E, Flexner C, Mildvan D; AIDS Clinical Trials Group A5073 Study Team. Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial. Arch Intern Med. 2009 Jul 13;169(13):1224-32. doi: 10.1001/archinternmed.2009.172.

Reference Type: RESULT

PMID: 19597072 (View on PubMed)

Flexner C, Tierney C, Gross R, Andrade A, Lalama C, Eshleman SH, Aberg J, Sanne I, Parsons T, Kashuba A, Rosenkranz SL, Kmack A, Ferguson E, Dehlinger M, Mildvan D; ACTG A5073 Study Team. Comparison of once-daily versus twice-daily combination antiretroviral therapy in treatment-naive patients: results of AIDS clinical trials group (ACTG) A5073, a 48-week randomized controlled trial. Clin Infect Dis. 2010 Apr 1;50(7):1041-52. doi: 10.1086/651118.

Reference Type: RESULT

PMID: 20192725 (View on PubMed)

Other Identifiers

10073

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5073

Identifier Type: -

Identifier Source: secondary_id

AACTG A5073

Identifier Type: -

Identifier Source: secondary_id

A5073

Identifier Type: -

Identifier Source: org_study_id