Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00357552

Purpose

Most anti-HIV regimens include a non-nucleoside reverse transcriptase inhibitor (NNRTI); however, some individuals fail on these regimens. The purpose of this study is to evaluate the safety and effectiveness of the protease inhibitor (PI) lopinavir/ritonavir (LPV/r) in HIV infected individuals who are failing an anti-HIV regimen that includes an NNRTI.

Condition	Intervention	Phase
HIV Infections	Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Lopinavir/Ritonavir	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Study of Lopinavir/Ritonavir in Participants Experiencing Virologic Relapse on NNRTI-Containing Regimens

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Ritonavir Lopinavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

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

Primary Outcome Measures:

Virologic success on LPV/r monotherapy [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Time to first new Grade 3 or 4 sign or symptom or laboratory toxicity [ Time Frame: During LPV/r monotherapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Patterns of HIV genotypic resistance mutations at study screening [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time to treatment failure, defined as the first occurrence of death, disease progression, or virologic failure; viral load less than 50 and less than 400 copies/ml from study entry to Week 104; change in CD4 count [ Time Frame: Study entry to Week 104 ] [ Designated as safety issue: Yes ]
HIV-related diagnoses and clinical events [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Resistance patterns in the protease gene of participants at the time of virologic failure or treatment intensification [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Drug adherence assessed as number of missed doses over 4-day recall and pill count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time to first new Grade 3 or 4 sign or symptom or laboratory toxicity following LPV/r intensification [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Evaluate the use of dried blood spots (DBS) for HIV-1 RNA and drug resistance testing [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Level of HIV-1 RNA as ascertained from paired DBS and plasma [ Time Frame: At study entry and Weeks 24 and 48 ] [ Designated as safety issue: No ]
HIV-1 viral sequence as ascertained from paired DBS and plasma [ Time Frame: At study entry and virologic failure ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	January 2008
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive lopinavir/ritonavir twice daily for up to 104 weeks.	Drug: Lopinavir/Ritonavir Twice daily
2: Experimental For patients who experience virologic failure, they will receive emtricitabine/tenofovir disoproxil fumarate once daily in addition to lopinavir/ritonavir twice daily.	Drug: Emtricitabine/Tenofovir disoproxil fumarate Once daily Drug: Lopinavir/Ritonavir Twice daily

Detailed Description:

Standard effective antiretroviral therapy for HIV infected individuals includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a PI or an NNRTI. However, three-drug regimens may not be ideal in resource-limited settings, where viral load and resistance testing may not be readily available. The purpose of this study is to evaluate the safety and efficacy of the PI LPV/r alone in treatment-experienced, PI-naive HIV infected individuals who are experiencing virologic failure on three-drug regimens.

This study will last 104 weeks. There will be up to two steps. All participants will enter Step 1 and receive LPV/r twice daily for up to 104 weeks. Participants who experience virologic failure will enter Step 2 and receive emtricitabine/tenofovir disoproxil fumarate once daily in addition to LPV/r twice daily for the remainder of the study.

There will be 16 study visits for Step 1 participants and 12 study visits for Step 2 participants. Blood collection and clinical assessment will occur at all visits; urine collection and resistance testing will occur at selected visits.

Eligibility

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

Criteria

Inclusion Criteria for Step 1 Participants:

HIV infected
Continuous treatment with a three-drug, NNRTI-containing regimen for at least 6 months prior to study entry
Viral load of 1,000 copies/ml or greater and less than 200,000 copies/ml
Negative pregnancy test within 48 hours of study entry
Willing to use acceptable forms of contraception for the duration of the study

Inclusion Criteria for Step 2 Participants:

Virologic failure on LPV/r monotherapy defined as viral load of 400 copies/ml or greater after 24 consecutive weeks on LPV/r monotherapy OR virologic failure after initial viral suppression on LPV/r monotherapy
Estimated creatinine clearance of 60 ml/min or greater
Negative pregnancy test within 48 hours of entry into Step 2

Exclusion Criteria for All Participants:

Prior use of any PI
Known allergy or sensitivity to study drugs
Current drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study participation
History of chronic hepatitis B infection
Acute therapy for any serious medical condition within 14 days of study entry
Certain abnormal laboratory values
Breastfeeding

Exclusion Criteria for Step I Participants:

Acute therapy for any serious medical condition within 14 days of study entry. For ongoing or chronic therapy, the participant must be on the treatment regimen for at least 14 days, and clinically stable prior to entry. If a potential participant has TB and has received treatment for more than 2 weeks, the TB treatment would have to be modified to include a rifabutin-containing regimen. TB compatible syndromes will also be carefully evaluated prior to entry.

Exclusion Criteria for Step 2 Participants:

Active opportunistic infection, including tuberculosis (TB)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357552

Contacts

Contact: Beatrice Kallungal, BS

301-628-3000

bkallungal@s-3.com

Locations

India
Y.R.G. Ctr. for AIDS Research and Education	Recruiting
Chennai, India, 60001-7
Contact: Aylur K Srikrishnan, MBA 91 (442) 254-2929 krish@yrgcare.org
Principal Investigator: Nagalingeshwaran Kumarasamy, MD, PhD
Tanzania, Moshi
Kilimanjaro Christian Medical CRS	Recruiting
Kilimanjaro Region, Moshi, Tanzania
Contact: Suzanne Fiorillo, MSPH 255-255-783659498 suzanne.fiorillo@duke.edu
Principal Investigator: John A. Crump, MB, ChB, DTM&H

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:	Nagalingeswaran Kumarasamy, MBBS, PhD	Y. R. Gaitonde Centre for AIDS Research and Education
Study Chair:	John Bartlett, MD	Division of Infectious Diseases, Duke University Medical Center

More Information

Additional Information:

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

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Click here for more information on HIV regimen failure This link exits the ClinicalTrials.gov site

Click here for more information on changing regimens 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:

Arribas JR, Pulido F, Delgado R, Lorenzo A, Miralles P, Arranz A, Gonzalez-Garcia JJ, Cepeda C, Hervas R, Pano JR, Gaya F, Carcas A, Montes ML, Costa JR, Pena JM. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study). J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):280-7.

Campo RE, Lalanne R, Tanner TJ, Jayaweera DT, Rodriguez AE, Fontaine L, Kolber MA. Lopinavir/ritonavir maintenance monotherapy after successful viral suppression with standard highly active antiretroviral therapy in HIV-1-infected patients. AIDS. 2005 Mar 4;19(4):447-9. No abstract available.

Joly V, Descamps D, Peytavin G, Touati F, Mentre F, Duval X, Delarue S, Yeni P, Brun-Vezinet F. Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs. Antimicrob Agents Chemother. 2004 Jan;48(1):172-5.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5230
Study First Received:	July 25, 2006
Last Updated:	April 10, 2009
ClinicalTrials.gov Identifier:	NCT00357552 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Treatment Experienced

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Lopinavir
Emtricitabine
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil
RNA Virus Infections

HIV Protease Inhibitors
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Ritonavir
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 08, 2010