Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy
21 febbraio 2018 aggiornato da: AIDS Clinical Trials Group
A Pilot Study of Lopinavir/Ritonavir in Participants Experiencing Virologic Relapse on NNRTI-Containing Regimens
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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
123
Fase
- Non applicabile
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Chennai, India
- Y.R.G Ctr, for AIDS Research and Education (11701)
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Lilongwe, Malawi
- University of North Carolina Lilongwe CRS (12001)
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Gauteng
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Johannesburg, Gauteng, Sud Africa
- Wits HIV CRS (11101)
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Chiang Mai, Tailandia, 50202
- Chiang Mai University ACTG CRS (11501)
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Moshi, Tanzania
- Kilimanjaro Christian Medical CRS
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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 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
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
- Willing to use acceptable forms of contraception for the duration of the study
Exclusion Criteria for All Participants:
- 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
Exclusion Criteria for Step I Participants:
- 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.
Exclusion Criteria for Step 2 Participants:
- Active opportunistic infection, including tuberculosis (TB)
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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.
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Once daily
Altri nomi:
Twice daily
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy
Lasso di tempo: From study entry to week 24
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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.
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From study entry to week 24
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Probability of Grade 3 or 4 Sign or Symptom, or Laboratory Toxicity Over 24 Weeks on Study.
Lasso di tempo: From study entry to week 24
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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.
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From study entry to week 24
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.
Lasso di tempo: Screening
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Number of screened subjects with at least one NNRTI, or NRTI-associated resistance mutation.
Resistance interpretations used the November 30, 2011 Stanford algorithm.
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Screening
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Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure.
Lasso di tempo: Study entry to Week 104
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25th percentile in weeks from study entry to treatment failure, defined as the first occurrence of death, disease progression, or virologic failure.
Virologic failure was defined as HIV-1 >= 400 copies/mL after week 24 or 2 consecutive HIV-1 RNA >= 400 copies/mL after week 16 following suppression on LPV/r monotherapy.
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Study entry to Week 104
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Number of Participants With Study-targeted Diagnoses and Clinical Events
Lasso di tempo: Study entry to week 104
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Cardiac disorders, Infections and infestations, Metabolism and nutrition disorders, Neoplasms benign, malignant and unspecified (including cysts and polyps), Pregnancy, puerperium and perinatal conditions, Vascular disorders, were specified a priori as study-targeted events by the study chair.
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Study entry to week 104
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Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure.
Lasso di tempo: At time of virologic failure
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Number of subjects with at least one new PI-associated resistance mutation at time of virologic failure.
Resistance interpretations used the May 6, 2009 Stanford algorithm.
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At time of virologic failure
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Percentage of Subjects Reporting Not Skipping Medications in the Last Month.
Lasso di tempo: Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
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The percentage of subjects reporting never missing medications in the last month.
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Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
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Time to First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification
Lasso di tempo: From LPV/r intensification to week 104
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25th percentile in weeks from study entry to first new grade 3 or 4 sign or symptom or laboratory toxicity following LPV/r intensification.
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.
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From LPV/r intensification to week 104
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Level of HIV-1 RNA as Ascertained From Paired DBS and Plasma
Lasso di tempo: At study entry and weeks 24 and 48
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Proportion of DBS samples with HIV-1 RNA level <= 400 copies/mL, proportion of plasma samples with HIV-1 RNA level <= 400 copies/mL and proportion of paired DBS and plasma samples that are concordant (both <= 400 copies/mL or both > 400 copies/mL).
Results are pooled over 4 different storage temperature conditions (-80C, -20C, 4C and room temperature).
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At study entry and weeks 24 and 48
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HIV-1 Viral Sequence as Ascertained From Paired DBS and Plasma
Lasso di tempo: At study entry and virologic failure
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HIV-1 viral sequencing as ascertained from paired DBS and plasma
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At study entry and virologic failure
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Proportion of Participants With Plasma HIV-1 RNA Levels < 400 Copies/mL From Baseline to Week 104
Lasso di tempo: At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
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At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
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Change in CD4+ Cell Counts From Study Entry to Week 104
Lasso di tempo: Study entry and week 104
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Study entry and week 104
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Cattedra di studio: Nagalingeswaran Kumarasamy, MBBS, PhD, Y. R. Gaitonde Centre for AIDS Research and Education
- Cattedra di studio: John Bartlett, MD, Division of Infectious Diseases, Duke University Medical Center
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
- 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.
- 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.
- 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.
- 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.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 gennaio 2008
Completamento primario (Effettivo)
1 ottobre 2010
Completamento dello studio (Effettivo)
1 maggio 2012
Date di iscrizione allo studio
Primo inviato
25 luglio 2006
Primo inviato che soddisfa i criteri di controllo qualità
25 luglio 2006
Primo Inserito (Stima)
27 luglio 2006
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
20 marzo 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
21 febbraio 2018
Ultimo verificato
1 febbraio 2018
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Infezioni da virus a RNA
- Malattie virali
- Infezioni
- Infezioni a trasmissione ematica
- Malattie trasmissibili
- Malattie sessualmente trasmissibili, virali
- Malattie trasmesse sessualmente
- Infezioni da lentivirus
- Infezioni da retroviridae
- Sindromi da deficit immunologico
- Malattie del sistema immunitario
- Infezioni da HIV
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antivirali
- Inibitori della trascrittasi inversa
- Inibitori della sintesi degli acidi nucleici
- Inibitori enzimatici
- Agenti anti-HIV
- Agenti antiretrovirali
- Inibitori della proteasi
- Inibitori del citocromo P-450 CYP3A
- Inibitori dell'enzima del citocromo P-450
- Inibitori della proteasi dell'HIV
- Inibitori virali della proteasi
- Tenofovir
- Emtricitabina
- Ritonavir
- Lopinavir
- Combinazione di farmaci Emtricitabina, Tenofovir disoproxil fumarato
Altri numeri di identificazione dello studio
- ACTG A5230
- 1U01AI068636 (Sovvenzione/contratto NIH degli Stati Uniti)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .