Safety and Effectiveness of Lopinavir/Ritonavir in Individuals Who Have Failed Prior HIV Therapy
- Conditions
- HIV Infections
- Interventions
- Registration Number
- NCT00357552
- Lead Sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 123
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LPV/r monotherapy Lopinavir/Ritonavir 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. LPV/r monotherapy Emtricitabine/Tenofovir disoproxil fumarate 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.
- Primary Outcome Measures
Name Time Method Probability of Grade 3 or 4 Sign or Symptom, or Laboratory Toxicity Over 24 Weeks on Study. 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.
Percentage of Enrolled Participants With Virologic Success at Week 24 on LPV/r Monotherapy 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.
- Secondary Outcome Measures
Name Time Method Percentage of Subjects Reporting Not Skipping Medications in the Last Month. Study entry and weeks 2, 4, 8, 12, 16, 20, and 24 The percentage of subjects reporting never missing medications in the last month.
Number of Participants With Study-targeted Diagnoses and Clinical Events 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.
Number of Subjects With at Least One New PI-associated Resistance Mutation at Time of Virologic Failure. 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.
Level of HIV-1 RNA as Ascertained From Paired DBS and Plasma 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).
Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening. Screening 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 First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification 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.
Change in CD4+ Cell Counts From Study Entry to Week 104 Study entry and week 104 Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure. 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.
HIV-1 Viral Sequence as Ascertained From Paired DBS and Plasma At study entry and virologic failure HIV-1 viral sequencing as ascertained from paired DBS and plasma
Proportion of Participants With Plasma HIV-1 RNA Levels < 400 Copies/mL From Baseline to Week 104 At Weeks 0, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92, 104
Trial Locations
- Locations (5)
University of North Carolina Lilongwe CRS (12001)
🇲🇼Lilongwe, Malawi
Y.R.G Ctr, for AIDS Research and Education (11701)
🇮🇳Chennai, India
Kilimanjaro Christian Medical CRS
🇹🇿Moshi, Tanzania
Chiang Mai University ACTG CRS (11501)
🇹ðŸ‡Chiang Mai, Thailand
Wits HIV CRS (11101)
🇿🇦Johannesburg, Gauteng, South Africa