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

21 février 2018 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

123

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Afrique du Sud
    • Gauteng
      • Johannesburg, Gauteng, Afrique du Sud
        • Wits HIV CRS (11101)
  • Inde
      • Chennai, Inde
        • Y.R.G Ctr, for AIDS Research and Education (11701)
  • Malawi
      • Lilongwe, Malawi
        • University of North Carolina Lilongwe CRS (12001)
  • Tanzanie
      • Moshi, Tanzanie
        • Kilimanjaro Christian Medical CRS
  • Thaïlande
      • Chiang Mai, Thaïlande, 50202
        • Chiang Mai University ACTG CRS (11501)

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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)

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Emtricitabine/Tenofovir disoproxil fumarate
Once daily
Autres noms:
  • Truvada
Médicament: Lopinavir/Ritonavir
Twice daily
Autres noms:
  • Kaletra, Aluvia

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy
Délai: From study entry to week 24
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.
Délai: From study entry to week 24
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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening.
Délai: Screening
Number of screened subjects with at least one NNRTI, or NRTI-associated resistance mutation. Resistance interpretations used the November 30, 2011 Stanford algorithm.
Screening
Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure.
Délai: Study entry to Week 104
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.
Study entry to Week 104
Number of Participants With Study-targeted Diagnoses and Clinical Events
Délai: Study entry to week 104
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.
Study entry to week 104
Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure.
Délai: At time of virologic failure
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.
At time of virologic failure
Percentage of Subjects Reporting Not Skipping Medications in the Last Month.
Délai: Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
The percentage of subjects reporting never missing medications in the last month.
Study entry and weeks 2, 4, 8, 12, 16, 20, and 24
Time to First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification
Délai: From LPV/r intensification to week 104
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.
From LPV/r intensification to week 104
Level of HIV-1 RNA as Ascertained From Paired DBS and Plasma
Délai: At study entry and weeks 24 and 48
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).
At study entry and weeks 24 and 48
HIV-1 Viral Sequence as Ascertained From Paired DBS and Plasma
Délai: At study entry and virologic failure
HIV-1 viral sequencing as ascertained from paired DBS and plasma
At study entry and virologic failure
Proportion of Participants With Plasma HIV-1 RNA Levels < 400 Copies/mL From Baseline to Week 104
Délai: At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
Change in CD4+ Cell Counts From Study Entry to Week 104
Délai: Study entry and week 104
Study entry and week 104

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

AIDS Clinical Trials Group

Collaborateurs

National Institute of Allergy and Infectious Diseases (NIAID)

Les enquêteurs

  • Chaise d'étude: Nagalingeswaran Kumarasamy, MBBS, PhD, Y. R. Gaitonde Centre for AIDS Research and Education
  • Chaise d'étude: John Bartlett, MD, Division of Infectious Diseases, Duke University Medical Center

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2008

Achèvement primaire (Réel)

1 octobre 2010

Achèvement de l'étude (Réel)

1 mai 2012

Dates d'inscription aux études

Première soumission

25 juillet 2006

Première soumission répondant aux critères de contrôle qualité

25 juillet 2006

Première publication (Estimation)

27 juillet 2006

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

20 mars 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 février 2018

Dernière vérification

1 février 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • ACTG A5230
  • 1U01AI068636 (Subvention/contrat des NIH des États-Unis)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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