Clinical Trial: Once-Daily PI/NNRTI Therapy Combinations for Treatment Naive, HIV Infected Patients in Resource-limited Conditions

This study is not yet open for patient recruitment.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

Taking anti-HIV drugs correctly is important to control HIV viral load and avoid drug resistance. Less complicated drug dosing may help promote medication adherence. This study will compare the effectiveness of 3 three-drug combinations in HIV infected patients starting their first HIV treatment regimens. Participants will be recruited from resource-poor communities in Africa, Asia, South America, Haiti, and the U.S.

Condition Treatment or Intervention Phase
HIV Infections
 Drug: Atazanavir
 Drug: Didanosine, enteric coated
 Drug: Efavirenz
 Drug: Emtricitabine
 Drug: Lamivudine/Zidovudine
 Drug: Tenofovir disoproxil fumarate
Phase IV

MedlinePlus related topics:  AIDS

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title: A Phase IV, Prospective, Randomized, Open-Label Evaluation of the Efficacy of Once-Daily Protease Inhibitor and Once-Daily Non-Nucleoside Reverse Transcriptase Inhibitor-Containing Therapy Combinations for Initial Treatment of HIV-1 Infected Individuals from Resource-Limited Setting (PEARLS) Trial

Further Study Details: 

Expected Total Enrollment:  1520

In developed countries, standard effective anti-HIV therapy for treatment-naive HIV infected patients includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). However, many HIV infected patients in resource-poor countries do not receive proper medical care for HIV infection. Medication adherence is a problem observed in all groups of HIV infected patients; non-adherence may be lessened with simplified medication dosing. This study will compare the effectiveness of 3 three-drug combinations in treatment-naive HIV infected patients in resource-limited settings. Patients for this trial will be recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.

Patients in this study will be randomly assigned to one of three arms. Arm A patients will receive lamivudine/zidovudine twice daily and efavirenz once daily. Arm B patients will receive emtricitabine, atazanavir, and enteric-coated didanosine once daily. Arm C patients will receive emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily.

This study will last approximately 48 weeks. A physical exam and blood collection will occur at entry and at ten study visits. Pill counts and patient interviews about adherence to their regimens will also occur at each visit. A patient experiencing virologic failure and either progression to AIDS or a significant decrease in CD4 cell count will be offered a switch from their current regimen to another regimen. Participants are encouraged to enroll in substudy A5185s, a study of HIV viral load in genital secretions.

Eligibility

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria for Step 1:

  • HIV-1 infected
  • Prior antiretroviral therapy for less than 7 days any time prior to study entry
  • CD4 count less than 300 cells/mm3
  • Willing to use acceptable means of contraception
  • Plans to stay in the area for the duration of study participation
  • Willing to adhere to study follow-up schedule

Exclusion Criteria for Step 1:

  • Acute therapy for serious medical illnesses within 14 days prior to study entry. Patients with serious infection who must continue with chronic maintenance therapy must be clinically stable and have completed at least 14 days of therapy prior to study entry.
  • Any condition that, in the opinion of the site investigator, would compromise the patient's ability to participate in the study
  • Radiation therapy or chemotherapy within 45 days prior to study entry. Systemic chemotherapy for treatment of Kaposi's sarcoma within 45 days of study entry is acceptable, provided the systemic chemotherapy is completed prior to entry.
  • Any immunomodulator, HIV vaccine, or other investigational therapy within 30 days prior to study entry. Patients taking tapered courses of corticosteroids for acute therapy for Pneumocystis carinii pneumonia (PCP) are not excluded.
  • Current alcohol or drug abuse that, in the opinion of the site investigator, would interfere with study requirements
  • Inflamed pancreas
  • Pregnancy
  • Allergy to any of the study drugs or their formulations
  • Heart rate less than 40 beats/min
  • History of untreated active 2nd or 3rd degree heart block
  • Certain medications
  • Currently detained in jail or for treatment of a psychiatric or physical illness
  • Vomiting or inability to swallow medications

Location Information


California
      Harbor General/UCLA, Torrance,  California,  90502-2052,  United States
Mario Guerrero, MD  310-222-3848    mguerrero@rei.edu 

      UCLA School of Medicine, Los Angeles,  California,  90095-1793,  United States
Deborah Tolenaar  310-825-1301    dtolenaar@mednet.ucla.edu 

Colorado
      Univ. of Colorado Health Sciences Center, Denver, Denver,  Colorado,  80262-3706,  United States
M. Graham Ray, RN, MSN  303-372-5535    graham.ray@uchsc.edu 

Missouri
      Washington University (St. Louis), St. Louis,  Missouri,  63108-2138,  United States
Michael Klebert, RN-C, MSN  314-454-0058    mklebert@im.wustl.edu 

New York
      Chelsea Clinic, New York,  New York,  10011,  United States
Todd Stroberg, RN  212-746-7198    tstrober@nyp.org 

      Columbia University, New York,  New York,  10032-3784,  United States
Mykyelle Crawford, RN, BSN  212-305-2665    mc675@columbia.edu 

North Carolina
      University of North Carolina, Chapel Hill,  North Carolina,  27514,  United States
Cheryl J. Marcus, RN, BSN  919-843-8761    cjm@med.unc.edu 

      The Moses H. Cone Memorial Hospital, Greensboro,  North Carolina,  27401-4001,  United States
Kim Epperson, RN  336-832-7888    kimepperson@mosescone.com 

      Wake County Department of Health, Chapel Hill,  North Carolina,  27514,  United States
Cheryl J. Marcus, RN, BSN  919-843-8761    cjm@med.unc.edu 

      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
Suzanne Aycock, RN, BSN, CCRC  (919) 684-8216    aycoc001@mc.duke.edu 

Pennsylvania
      University of Pennsylvania, Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
Joseph Quinn, RN  215-349-8092    joseph.quinn@uphs.upenn.edu 

      Presbyterian Medical Center - Univ. of PA, Philadelphia,  Pennsylvania,  19104,  United States
Joseph Quinn, RN  215-349-8092    joseph.quinn@uphs.upenn.edu 

Rhode Island
      The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Joan Gormley, BSN  401-793-4396    jgormley@lifespan.org 

      Rhode Island Hospital, Providence,  Rhode Island,  02906,  United States
Joan Gormley, BSN  401-793-4396    jgormley@lifespan.org 

      Stanley Street Treatment and Resource, Providence,  Rhode Island,  02906,  United States
Joan Gormley, BSN  401-793-4396    jgormley@lifespan.org 

Tennessee
      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States
Janet Nicotera, RN, BSN  615-467-0154  Ext. 108    janet.nicotera@vanderbilt.edu 

Texas
      University of Texas, Galveston, Galveston,  Texas,  77555-0435,  United States
Gerianne Casey, RN  409-747-0219    gecasey@utmb.edu 

Malawi
      University of North Carolina Project (UNC Project), Lilongwe,  Malawi
Cecelia Kanyama  (265) 175-5056 

South Africa
      University of Witwatersrand, Johannesburg,  South Africa
Pauline S Vunandlala, BSc  27 11 717 2810    idsyndicate@witshealth.co.za 

Zimbabwe
      University of Zimbabwe, Harare,  Zimbabwe
Patricia Mutama  263-4-701-326    pmutama@uzcrc.co.zw 

Study chairs or principal investigators

Thomas B. Campbell, MD,  Study Chair,  University of Colorado   
Timothy Flanigan, MD,  Study Chair,  Miriam Hospital   
James Hakim, MscClinEpi, FRCP,  Study Chair,  Department of Medicine, University of Zimbabwe   
Nagalingeswaran Kumarasamy, MD,  Study Chair,  YRG Centre for AIDS Research and Education   

More Information

Click here for more information about atazanavir

Click here for more information about didanosine

Click here for more information about efavirenz

Click here for more information about emtricitabine

Click here for more information about lamivudine/zidovudine

Click here for more information about tenofovir disoproxil fumarate

Click here for more information about nucleoside reverse transcriptase inhibitors [NRTIs]

Click here for more information about non-nucleoside reverse transcriptase inhibitors [NNRTIs]

Click here for more information about protease inhibitors [PIs]

Haga clic aquí para ver información sobre este ensayo clínico en español.

Publications

Knobel H, Vallecillo G, Guelar A, Pedrol E, Soler A, Carmona A, Saballs P, Gonzalez A, Gimeno JL, Colomes JL. Simplified therapy with Zidovudine, Lamivudine, and abacavir for very nonadherent, treatment-failing patients. HIV Clin Trials. 2004 Mar-Apr;5(2):65-73.

Lange J. The power of simplicity. Int J STD AIDS. 2003 Oct;14 Suppl 1:15-9. Review.

Piliero PJ, Colagreco JP. Simplified regimens for treating HIV infection and AIDS. J Am Acad Nurse Pract. 2003 Jul;15(7):305-12. Review.

Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dube MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS; AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med. 2003 Dec 11;349(24):2293-303.

Taburet AM, Paci-Bonaventure S, Peytavin G, Molina JM. Once-daily administration of antiretrovirals: pharmacokinetics of emerging therapies. Clin Pharmacokinet. 2003;42(14):1179-91. Review.

Study ID Numbers:  ACTG A5175; PEARLS; A5185s
Record last reviewed:  April 2005
Last Updated:  April 7, 2005
Record first received:  June 7, 2004
ClinicalTrials.gov Identifier:  NCT00084136
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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