Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy

NCT00357552 | Completed Results DMC

• 2 other identifiers: ACTG A52301U01AI068636
• Study Type: interventional
• Target: 123
• Locations: 5 countries
• Sites: 5

Brief Summary

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.

Conditions

HIV Infections

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (2)

• Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy

  Virologic success at week 24 on LPV/r monotherapy was defined as remaining on LPV/r monotherapy at week 24 without prior virologic failure. Virologic failure was met with either of these two conditions: (i) failure to suppress HIV-1 RNA to \< 400 copies/mL by week 24 or (ii) confirmed HIV-1 RNA \>= 400 copies/mL after confirmed HIV-1 RNA \< 400 copies/mL.

  From study entry to week 24

• Probability of Grade 3 or 4 Sign or Symptom, or Laboratory Toxicity Over 24 Weeks on Study.

  Probability of Grade 3 or 4 sign or symptom, or laboratory toxicity over 24 weeks on study using Kaplan-Meier estimates of the cumulative probability of Grade 3 or 4 sign or symptom, or laboratory toxicity at week 24. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

  From study entry to week 24

Secondary Outcomes (10)

• Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.

  Screening

• Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure.

  Study entry to Week 104

• Number of Participants With Study-targeted Diagnoses and Clinical Events

  Study entry to week 104

• Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure.

  At time of virologic failure

• Percentage of Subjects Reporting Not Skipping Medications in the Last Month.

  Study entry and weeks 2, 4, 8, 12, 16, 20, and 24

Study Arms (1)

LPV/r monotherapy

EXPERIMENTAL

Participants will receive lopinavir/ritonavir twice daily for up to 104 weeks. Upon confirmation of virologic failure, emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) once a day will be added to their regimen.

Drug: Emtricitabine/Tenofovir disoproxil fumarate; Drug: Lopinavir/Ritonavir

Interventions

Emtricitabine/Tenofovir disoproxil fumarate DRUG

Once daily

Also known as: Truvada

LPV/r monotherapy

Lopinavir/Ritonavir DRUG

Twice daily

Also known as: Kaletra, Aluvia

LPV/r monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 or equal to 200,000 copies/ml obtained within 30 days of study entry
• Negative pregnancy test within 48 hours of study entry
• Willing to use acceptable forms of contraception for the duration of the study
• Laboratory values obtained within 30 days of study entry:
• Hemoglobin greater or equal to 8.0 g/dL
• Platelet count greater or equal to 50,000/mm3
• Estimated Creatinine Clearance greater or equal to 60 mL/min x ULN
• AST (SGOT), ALT (SGPT) and alkaline phosphatase \< 3 x ULN
• Total bilirubin less or equal to 2.5 x ULN
• Ability and willingness of participant or legal guardian/representative to give informed consent
• 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

You may not qualify if:

• Breastfeeding
• Known allergy or sensitivity to study drugs
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study adherence to study requirements
• History of chronic hepatitis B infection
• Prior use of any protease inhibitor treatment
• 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.
• \- Active opportunistic infection, including tuberculosis (TB)

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (5)

Y.R.G Ctr, for AIDS Research and Education (11701)

Chennai, India

Location

University of North Carolina Lilongwe CRS (12001)

Lilongwe, Malawi

Location

Wits HIV CRS (11101)

Johannesburg, Gauteng, South Africa

Location

Kilimanjaro Christian Medical CRS

Moshi, Tanzania

Location

Chiang Mai University ACTG CRS (11501)

Chiang Mai, 50202, Thailand

Location

Related Publications (5)

• 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. doi: 10.1097/01.qai.0000180077.59159.f4.

  PMID: 16249701 BACKGROUND

• 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. doi: 10.1097/01.aids.0000161777.38438.ed. No abstract available.

  PMID: 15750401 BACKGROUND

• 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. doi: 10.1128/AAC.48.1.172-175.2004.

  PMID: 14693536 BACKGROUND

• Bartlett JA, Ribaudo HJ, Wallis CL, Aga E, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Kallungal BA, Kumarasamy N. Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings. AIDS. 2012 Jul 17;26(11):1345-54. doi: 10.1097/QAD.0b013e328353b066.

  PMID: 22441252 RESULT

• Kumarasamy N, Aga E, Ribaudo HJ, Wallis CL, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Bartlett JA. Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230. Clin Infect Dis. 2015 May 15;60(10):1552-8. doi: 10.1093/cid/civ109. Epub 2015 Feb 18.

  PMID: 25694653 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Lopinavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyrimidinones

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2006
• First Posted: July 27, 2006
• Study Start: January 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: May 1, 2012
• Last Updated: March 20, 2018
• Results First Posted: September 25, 2012

Record last verified: 2018-02

Locations

IN (1); TA (1); TH (1); MA (1); ZA (1)