Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy
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.
Drug: Emtricitabine/Tenofovir disoproxil fumarate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Lopinavir/Ritonavir in Participants Experiencing Virologic Relapse on NNRTI-Containing Regimens|
- Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy [ Time Frame: From study entry to week 24 ] [ Designated as safety issue: No ]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.
- Probability of Grade 3 or 4 Sign or Symptom, or Laboratory Toxicity Over 24 Weeks on Study. [ Time Frame: From study entry to week 24 ] [ Designated as safety issue: Yes ]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.
- Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening. [ Time Frame: Screening ] [ Designated as safety issue: No ]Number of screened subjects with at least one NNRTI, or NRTI-associated resistance mutation. Resistance interpretations used the November 30, 2011 Stanford algorithm.
- Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure. [ Time Frame: Study entry to Week 104 ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Study-targeted Diagnoses and Clinical Events [ Time Frame: Study entry to week 104 ] [ Designated as safety issue: No ]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.
- Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure. [ Time Frame: At time of virologic failure ] [ Designated as safety issue: No ]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.
- Percentage of Subjects Reporting Not Skipping Medications in the Last Month. [ Time Frame: Study entry and weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]The percentage of subjects reporting never missing medications in the last month.
- Time to First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification [ Time Frame: From LPV/r intensification to week 104 ] [ Designated as safety issue: Yes ]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.
- 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 ]
- Proportion of Participants With Plasma HIV-1 RNA Levels < 400 Copies/mL From Baseline to Week 104 [ Time Frame: At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104 ] [ Designated as safety issue: No ]
- Change in CD4+ Cell Counts From Study Entry to Week 104 [ Time Frame: Study entry and week 104 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||May 2012|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: LPV/r monotherapy
Participants will receive lopinavir/ritonavir twice daily for up to 104 weeks. Upon confirmation of virologic failure, emtricitabine (FTC)/tenofovir (TDF) once a day will be added to their regimen.
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Other Name: TruvadaDrug: Lopinavir/Ritonavir
Other Name: Kaletra, Aluvia
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00357552
|Y.R.G Ctr, for AIDS Research and Education (11701)|
|University of North Carolina Lilongwe CRS (12001)|
|Wits HIV CRS (11101)|
|Johannesburg, Gauteng, South Africa|
|Kilimanjaro Christian Medical CRS|
|Kilimanjaro Region, Moshi, Tanzania|
|Chiang Mai University ACTG CRS (11501)|
|Chiang Mai, Thailand, 50202|
|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|