Once-Daily PI/NNRTI Therapy Combinations for Treatment Naive, HIV Infected Patients in Resource-Limited Conditions - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00084136

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 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants will be recruited from resource-poor communities in Africa, Asia, South America, Haiti, and the United States.

Condition	Intervention	Phase
HIV Infections	Drug: Atazanavir Drug: Didanosine (enteric-coated) Drug: Efavirenz Drug: Emtricitabine Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Lamivudine/Zidovudine	Phase IV

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Lamivudine Didanosine Efavirenz Atazanavir sulfate BMS 232632 Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

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 Settings (PEARLS) Trial

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Time to treatment failure, defined as the time from study entry to the first occurrence of virologic failure, disease progression, or death [ Time Frame: At least 12 weeks following study entry. Virologic failure will be measured at the Week 16 visit or later. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to discontinuation of intitial antiretroviral therapy [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
Time to immunologic failure [ Time Frame: At or after Week 48 ] [ Designated as safety issue: No ]
Change in CD4 count [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
Time to first dose modification or Grade 3 or 4 toxicity [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
Viral load less than 400 copies/ml [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
Time to loss of virologic response [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	1574
Study Start Date:	April 2005
Estimated Study Completion Date:	August 2007
Estimated Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Arm A participants will receive lamivudine/zidovudine and efavirenz for 48 weeks unless virologic failure due to drug resistance occurs	Drug: Efavirenz 600 mg taken orally daily Drug: Lamivudine/Zidovudine 150 mg/300 mg taken orally twice daily
B: Experimental Arm B participants will receive emtricitabine, atazanavir, and enteric-coated didanosine for 48 weeks unless virologic failure due to drug resistance occurs	Drug: Atazanavir 400 mg taken orally daily Drug: Didanosine (enteric-coated) 400 mg taken orally daily Drug: Efavirenz 600 mg taken orally daily Drug: Emtricitabine 200 mg taken orally daily
C: Experimental Arm C participants will receive emtricitabine/tenofovir disoproxil fumarate and efavirenz for 48 weeks unless virologic failure due to drug resistance occurs	Drug: Efavirenz 600 mg taken orally daily Drug: Emtricitabine 200 mg taken orally daily Drug: Emtricitabine/Tenofovir disoproxil fumarate 200 mg/300 mg taken orally once daily

Detailed Description:

In developed countries, standard effective antiretroviral (ARV) therapy for treatment-naive HIV infected people includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, many HIV infected individuals 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 individuals; nonadherence may be lessened with simplified medication dosing. This study will compare the effectiveness of 3 three-drug combinations in treatment-naive HIV infected individuals in resource-limited settings. Trial participants will be recruited in Africa (Malawi, South Africa, Zimbabwe), Asia (India, Thailand), South America (Brazil, Peru), Haiti, and the United States.

This study will last 48 weeks and has two steps. All participants will enter Step 1 and will be randomly assigned to one of three arms. Arm A participants will receive lamivudine/zidovudine twice daily and efavirenz once daily. Arm B participants will receive emtricitabine, atazanavir, and enteric-coated didanosine once daily. Arm C participants will receive emtricitabine, tenofovir disoproxil fumarate, and efavirenz once daily.

Step 1 participants who experience virologic failure due to drug resistance will enter Step 2. Step 2 participants will be assigned to one of three arms, based on drug resistance patterns causing Step 1 failure. Participants from Arm A or C in Step 1 will receive two NRTIs and one or more PIs in Step 2. Participants from Arm B in Step 1 will receive two NRTIs and efavirenz in Step 2.

In each step, a physical exam and blood collection will occur at entry and at most study visits. Pill counts and patient interviews about adherence to their regimens will also occur at most visits. 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 ACTG A5185s, a study of HIV viral load in genital secretions.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for Step 1:

HIV-1 infected
Prior ARV therapy for 7 days or less at any time prior to study entry
CD4 count less than 300 cells/mm3 within 90 days prior to study entry
Viral load test within 45 days prior to study entry
Plans to stay in the area for the duration of the study
Willing to adhere to study follow-up schedule
Agrees to use acceptable forms of contraception for the duration of the study

Inclusion Criteria for Step 2:

Virologic failure, defined as two successive viral load tests of 1000 copies/ml or greater OR either progression to AIDS after at least 12 weeks following study entry OR a decrease in CD4 count to less than 50% of the Step 1 maximum in absence of confirmed virologic failure after at least 12 weeks following study entry. More information on this criterion can be found in the protocol.
Received counseling on treatment adherence
Willing to switch to a new ARV treatment regimen
Site investigator recommends a new ARV regimen for the management of presumed or documented drug resistance
Received administrative approval to enter Step 2

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.
Certain abnormal laboratory values
Radiation therapy or chemotherapy within 45 days prior to study entry. Patients on systemic chemotherapy for treatment of Kaposi's sarcoma within 45 days of study entry are not excluded, provided the chemotherapy is completed prior to study 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 participation
Inflamed pancreas within 3 years prior to study entry
Currently enrolled in ACTG A5001 or A5164
Allergy/sensitivity to any of the study drugs or their formulations
Heart rate less than 40 beats/min
History of untreated, active second- or third-degree heart block
Require certain medications
Currently detained in jail or for treatment of a psychiatric or physical illness
Vomiting or inability to swallow medications
Any condition that, in the opinion of the site investigator, would compromise study participation
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084136

Show 46 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:	Thomas B. Campbell, MD	University of Colorado at Denver and Health Sciences Center
Study Chair:	Timothy Flanigan, MD	The Miriam Hospital
Study Chair:	James Hakim, MscClinEpi, FRCP	Department of Medicine, University of Zimbabwe
Study Chair:	Nagalingeswaran Kumarasamy, MD	Centre for AIDS Research and Education

More Information

Click here for more information about atazanavir This link exits the ClinicalTrials.gov site

Click here for more information about didanosine This link exits the ClinicalTrials.gov site

Click here for more information about efavirenz This link exits the ClinicalTrials.gov site

Click here for more information about emtricitabine This link exits the ClinicalTrials.gov site

Click here for more information about lamivudine/zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about nucleoside reverse transcriptase inhibitors [NRTIs] This link exits the ClinicalTrials.gov site

Click here for more information about non-nucleoside reverse transcriptase inhibitors [NNRTIs] This link exits the ClinicalTrials.gov site

Click here for more information about protease inhibitors [PIs] This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Publications:

Bartlett JA, Johnson J, Herrera G, Sosa N, Rodriguez A, Liao Q, Griffith S, Irlbeck D, Shaefer MS; for the Clinically Significant Long-term Antiretroviral Sequential Sequencing Study (CLASS) Team. Long-Term Results of Initial Therapy With Abacavir and Lamivudine Combined With Efavirenz, Amprenavir/Ritonavir, or Stavudine. J Acquir Immune Defic Syndr. 2006 Sep 7; [Epub ahead of print]

Saag MS. Initiation of antiretroviral therapy: implications of recent findings. Top HIV Med. 2004 Jul-Aug;12(3):83-8. Review.

Tapper ML, Daar ES, Piliero PJ, Smith K, Steinhart C. Strategies for initiating combination antiretroviral therapy. AIDS Patient Care STDS. 2005 Apr;19(4):224-38. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5175, PEARLS, A5185s, 5-K24-AI051966-03
Study First Received:	June 7, 2004
Last Updated:	September 10, 2008
ClinicalTrials.gov Identifier:	NCT00084136
Health Authority:	United States: Federal Government

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

Treatment Naive
Adherence
Drug Resistance
Treatment Failure

Study placed in the following topic categories:

Efavirenz
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Zidovudine
Lamivudine
Atazanavir
Immunologic Deficiency Syndromes
Virus Diseases

Didanosine
Emtricitabine
HIV Infections
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009