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.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: lopinavir/ritonavir  Drug: emtricitabine  Drug: stavudine  Drug: tenofovir DF	Phase II

Further Study Details: 

Expected Total Enrollment:  375

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

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

California
      Univ of California, Davis Med Ctr, Sacramento,  California,  95814,  United States
      University of Southern California, Los Angeles,  California,  90033-1079,  United States
      University of California, San Diego Antiviral Rese, San Diego,  California,  92103,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Florida
      Univ of Miami, Miami,  Florida,  33136,  United States
Hawaii
      University of Hawaii, Honolulu,  Hawaii,  96816-2396,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  46202-5250,  United States
      Methodist Hosp of Indiana, Indianapolis,  Indiana,  46202-1261,  United States
      Wishard Hosp, Indianapolis,  Indiana,  46202,  United States
Maryland
      Univ of Maryland, Institute of Human Virology, Baltimore,  Maryland,  21201,  United States
      Johns Hopkins Univ, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455-0392,  United States
New York
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      Univ of Rochester Med Ctr, Rochester,  New York,  14215,  United States
      Community Health Network, Inc, Rochester,  New York,  14642-0001,  United States
      McCree McCuller Wellness Center at the Connection, Rochester,  New York,  14642-0001,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  27514,  United States
      The Moses H. Cone Memorial Hosp, Greensboro,  North Carolina,  27401-1004,  United States
Ohio
      MetroHealth Med Ctr, Cleveland,  Ohio,  44109-1998,  United States
      Ohio State University, Columbus,  Ohio,  United States
      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States
      Case Western Reserve University, Cleveland,  Ohio,  44106-5083,  United States
Pennsylvania
      Univ of Pennsylvania, Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      University of Pittsburgh, Pittsburgh,  Pennsylvania,  15213-2582,  United States
Rhode Island
      Miriam Hosp/Brown Univ, Providence,  Rhode Island,  02906,  United States
      Rhode Island Hospital, Providence,  Rhode Island,  02906,  United States
      Stanley Street Treatment and Resource, Providence,  Rhode Island,  02906,  United States
Tennessee
      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98104,  United States
Puerto Rico
      Univ of Puerto Rico, San Juan,  00936-5067,  Puerto Rico
South Africa, Johnnesburg
      University of Witwatersrand, Parktown/Gauteng,  Johnnesburg,  South Africa

Study chairs or principal investigators

Donna Mildvan, MD,  Study Chair,  Beth Israel Medical Center   
Charles Flexner, MD,  Study Chair,  Johns Hopkins University Hospital   

Study ID Numbers:  ACTG A5073; AACTG A5073
Record last reviewed:  March 2005
Last Updated:  April 7, 2005
Record first received:  May 10, 2002
ClinicalTrials.gov Identifier:  NCT00036452
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08