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

NCT ID: NCT00357552

Last Updated: 2018-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2012-05-31

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.

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. All participants will receive LPV/r twice daily for up to 104 weeks. Participants who experience virologic failure will 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 participants on LPV/r monotherapy and 12 study visits for participants who have intensified LPV/r with emtricitabine/tenofovir disoproxil fumarate. Blood collection and clinical assessment will occur at all visits; urine collection and resistance testing will occur at selected visits.

Conditions

HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LPV/r monotherapy

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.

Group Type: EXPERIMENTAL

Emtricitabine/Tenofovir disoproxil fumarate

Intervention Type: DRUG

Once daily

Lopinavir/Ritonavir

Intervention Type: DRUG

Twice daily

Interventions

Emtricitabine/Tenofovir disoproxil fumarate

Once daily

Intervention Type: DRUG

Lopinavir/Ritonavir

Twice daily

Intervention Type: DRUG

Other Intervention Names

Truvada; Kaletra, Aluvia

Eligibility Criteria

Inclusion Criteria

• 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
• Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nagalingeswaran Kumarasamy, MBBS, PhD

Role: STUDY_CHAIR

Y. R. Gaitonde Centre for AIDS Research and Education

John Bartlett, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, Duke University Medical Center

Locations

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

Chennai, , India

University of North Carolina Lilongwe CRS (12001)

Lilongwe, , Malawi

Wits HIV CRS (11101)

Johannesburg, Gauteng, South Africa

Kilimanjaro Christian Medical CRS

Moshi, , Tanzania

Chiang Mai University ACTG CRS (11501)

Chiang Mai, , Thailand

Countries

India; Malawi; South Africa; Tanzania; Thailand

References

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.

Reference Type: BACKGROUND

PMID: 16249701 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15750401 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14693536 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22441252 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25694653 (View on PubMed)

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5230

Identifier Type: -

Identifier Source: org_study_id