Clinical trial NCT00036452: A Study to Compare Anti-HIV Drugs Given Twice a Day or Once a Day, With or Without Direct Observation
Official title: A Randomized, Phase II, Open Label Study to Compare Twice Daily and Once Daily Potent Antiretroviral Therapy and to Compare Self-Administered Therapy and Therapy Administered Under Direct Observation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-05-13
Enrollment: 402
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Sacramento
country: United States
facility: Univ. of California Davis Med. Ctr., ACTU
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Fall River
country: United States
facility: SSTAR, Family Healthcare Ctr.
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Rochester
country: United States
facility: AIDS Care CRS
state: New York
city: Rochester
country: United States
facility: McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease, Wendover Medical Center CRS
state: North Carolina
city: Raleigh
country: United States
facility: Wake County Health and Human Services CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hosp. ACTG CRS
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS
state: Tennessee
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
city: Johannesburg
country: South Africa
facility: Wits HIV CRS
state: Gauteng
Study officials:
affiliation: Beth Israel Medical Center
name: Donna Mildvan, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University Hospital
name: Charles Flexner, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.