Atazanavir/Ritonavir Maintenance Therapy

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ClinicalTrials.gov Identifier: NCT00084019

Recruitment Status : Completed

First Posted : June 7, 2004

Last Update Posted : June 3, 2014

Sponsor:

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

Long-term side effects, the expense of medications, and the difficulty of taking medications continuously for long periods of time are all problems with complicated anti-HIV drug regimens. The purpose of this study is to determine whether two drugs, atazanavir (ATV) and ritonavir (RTV), will control HIV infection when taken together without any other anti-HIV drugs after 48 weeks of viral suppression.

Hypothesis: Simplified maintenance therapy with ATV and RTV alone after virologic suppression does not markedly increase the risk of virologic failure.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Atazanavir Drug: Ritonavir	Not Applicable

Detailed Description:

The expense, difficulty, and long-term adverse events associated with sustained adherence to combination antiretroviral therapy emphasize the need for simpler, alternative treatment strategies for HIV infection. Studies have shown that single protease inhibitor (PI) maintenance therapy may provide sufficient virologic suppression while reducing the risk of nucleoside reverse transcriptase inhibitor (NRTI)-associated metabolic complications. However, it is not known whether ritonavir-boosted atazanavir (ATV/RTV) maintenance therapy would be effective in controlling HIV replication in the genital compartments and whether viral load testing by blood collection would be effective in detecting elevated levels of HIV in the genital compartments. This study will determine whether simplified maintenance therapy with ATV/RTV after 48-week virologic suppression will increase the likelihood of virologic failure.

This study will last 54 weeks. Participants will undergo an electrocardiogram (EKG) at screening. At study start, participants will switch from their current PIs to ATV/RTV and stay on their current NRTIs until Week 6, when they will discontinue their NRTIs and remain on a maintenance regimen of ATV/RTV alone for the duration of the study. Study visits will take place at Weeks 3 and 6, then every 4 weeks until Week 30, then every 8 weeks until the end of the study at Week 54. Medication assessment, physical exam, and blood work will occur at each study visit. At Week 30, viral load will be measured in the genital secretions of both male and female study participants.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	36 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Prospective, Open-Label, Pilot Trial of Regimen Simplification to Atazanavir/Ritonavir Alone as Maintenance Antiretroviral Therapy After Sustained Virologic Suppression
Study Start Date :	July 2004
Actual Study Completion Date :	May 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Atazanavir Atazanavir sulfate

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

Virologic failure, defined as 2 consecutive viral load measurements of 200 copies/ml or greater, at or before Week 30 (24 weeks on ATV/RTV alone)

Secondary Outcome Measures :

Grade 3 and 4 laboratory abnormalities and signs and symptoms
time to treatment discontinuation because of toxicity or intolerance
virologic failure at or before Week 54
viral load determined by modified ultrasensitive RT-PCR assay
minor PI variants at virologic failure
total cholesterol, high-density lipoprotein (HDL) cholesterol, calculated low-density lipoprotein (LDL) cholesterol, and triglycerides
CD4 cell count and percentages at Weeks 30 and 54
self-reported adherence scores
plasma drug levels characterized by Cmin and AUC
detectable viral load in the genital compartment at Week 30

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV infected
On first antiretroviral regimen, including at least 2 NRTIs and 1 PI, for at least 48 weeks immediately prior to study entry
CD4 count of 250 cells/mm3 or greater
Viral load less than 50 copies/ml within 30 days prior to entry
Willing to use acceptable methods of contraception

Exclusion Criteria:

Current or prior use of an NNRTI
Certain PI mutations
Hepatitis B infection within 90 days prior to study entry
Certain therapies or medications within 30 days prior to study entry
Heartbeat abnormalities or symptoms potentially related to heart block, such as unexplained fainting, dizziness, or palpitations, occurring within 180 days prior to study entry
Drug or alcohol use or dependence that would interfere with adherence to the study requirements
Serious illness requiring systemic treatment or hospitalization until the participant either completes therapy or has been clinically stable on therapy for at least 14 days prior to study entry
Allergy or sensitivity to study medications or their formulations
Current involuntarily incarceration for treatment of either a mental or physical illness
Treatment for an active AIDS-defining opportunistic infection within 30 days prior to screening
Pregnant or breastfeeding

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00084019

Locations


United States, California
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, United States, 94304-5350
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States, 52242
United States, Nebraska
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States, 68198-9500
United States, New York
Weill Cornell Chelsea CRS
New York, New York, United States, 10011
United States, North Carolina
Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati CRS
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Dallas VAMC
Dallas, Texas, United States, 75216
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, Puerto Rico, 00935

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Susan Swindells, MD	University of Nebraska

More Information

Publications of Results:

Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon J, Mellors JW; AIDS Clinical Trials Group 5201 Study Team. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA. 2006 Aug 16;296(7):806-14.

Other Publications:

Havlir DV, Marschner IC, Hirsch MS, Collier AC, Tebas P, Bassett RL, Ioannidis JP, Holohan MK, Leavitt R, Boone G, Richman DD. Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N Engl J Med. 1998 Oct 29;339(18):1261-8.

Pialoux G, Raffi F, Brun-Vezinet F, Meiffrédy V, Flandre P, Gastaut JA, Dellamonica P, Yeni P, Delfraissy JF, Aboulker JP. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1-infected patients. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team. N Engl J Med. 1998 Oct 29;339(18):1269-76.

Reijers MH, Weverling GJ, Jurriaans S, Wit FW, Weigel HM, Ten Kate RW, Mulder JW, Frissen PH, van Leeuwen R, Reiss P, Schuitemaker H, de Wolf F, Lange JM. Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study. Lancet. 1998 Jul 18;352(9123):185-90.

Kahlert C, Hupfer M, Wagels T, Bueche D, Fierz W, Walker UA, Vernazza PL. Ritonavir boosted indinavir treatment as a simplified maintenance "mono"-therapy for HIV infection. AIDS. 2004 Apr 9;18(6):955-7.

Kelly M. Induction-maintenance antiretroviral strategies to reduce long-term toxicity. J HIV Ther. 2003 Feb;8(1):11-4. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McKinnon JE, Mailliard RB, Swindells S, Wilkin TJ, Borowski L, Roper JM, Bastow B, Kearney M, Wiegand A, Mellors JW, Rinaldo CR; A5201 study team. Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201). PLoS One. 2014 May 6;9(5):e95524. doi: 10.1371/journal.pone.0095524. eCollection 2014.

Wilkin TJ, McKinnon JE, DiRienzo AG, Mollan K, Fletcher CV, Margolis DM, Bastow B, Thal G, Woodward W, Godfrey C, Wiegand A, Maldarelli F, Palmer S, Coffin JM, Mellors JW, Swindells S. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes. J Infect Dis. 2009 Mar 15;199(6):866-71. doi: 10.1086/597119.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00084019 History of Changes
Other Study ID Numbers:	A5201 10096 ( Registry Identifier: DAIDS ES ) ACTG A5201
First Posted:	June 7, 2004 Key Record Dates
Last Update Posted:	June 3, 2014
Last Verified:	June 2014

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


Treatment Experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Atazanavir Sulfate	HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

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