Atazanavir/Ritonavir Maintenance Therapy

HIV Infections Clinical Trial

Official title:

A Prospective, Open-Label, Pilot Trial of Regimen Simplification to Atazanavir/Ritonavir Alone as Maintenance Antiretroviral Therapy After Sustained Virologic Suppression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00084019
• Other study ID #: A5201
• Secondary ID: 10096ACTG A5201
• Status: Completed
• Phase: N/A
• Start date: July 2004
• Est. completion date: May 2006

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Atazanavir

• Ritonavir

Locations

Country	Name	City	State
Puerto Rico	Puerto Rico AIDS Clinical Trials Unit CRS	San Juan
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Chapel Hill CRS	Chapel Hill	North Carolina
United States	Cincinnati CRS	Cincinnati	Ohio
United States	Dallas VAMC	Dallas	Texas
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa
United States	Weill Cornell Chelsea CRS	New York	New York
United States	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska
United States	Stanford AIDS Clinical Trials Unit CRS	Palo Alto	California
United States	University of Pittsburgh CRS	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (6)

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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 — View Citation

Outcome

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

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