HIV Infections
Conditions
Keywords
HIV, Kaletra, treatment Experienced
Brief summary
Kaletra (a combination drug with lopinavir and ritonavir) is one of a few effective medications that are approved and available for young children who are HIV+. The liquid form is reported to have a very nasty taste and presents difficulties for the children who must take the medication twice a day and for their parents who must enforce the medication regimen. The children are often well into their teens before they weigh enough to be able to take the adult dose tablet (200mg/50mg). A new smaller dose tablet (100mg/25mg) is now available. However, it is not known if the liquid and tablet act the same in children. The purpose of this study is to switch children from the baseline treatment with the liquid to the study intervention treatment with 100mg/25mg tablet form of Kaletra. The study will compare children pre-switch and post-switch in terms of how well their HIV is controlled . Comparisons of parent and child satisfaction will also be made. Eight to 10 HIV+ children currently well managed with a medications including liquid Kaletra will be invited to switch from the liquid to the low dose Kaletra tablet. The parent and/or child will complete a satisfaction survey for the liquid Kaletra and lab values will be taken from the chart. At the time of the switch and 1, 3 and 6 months post switch blood tests will be drawn and the parent and/or child will complete the satisfaction survey. In addition, at the switch and 1 month post switch, a day will be spent in clinic with 5 blood draws to see how much of the drug is in the blood stream at different times after the medicine is taken.
Interventions
DRUGLow dose Kaletra tablets
Lopinavir/Ritonavir tablets 100mg/25mg
Sponsors
Abbott
Phoenix Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* HIV+ children aged 3-18. * Baseline treatment includes liquid Kaletra * currently on a stable (on same regimen \> 3 months, Viral Load\< 5,000), Highly Active Antiretroviral Therapy (HAART) regimen * able to take pills or willing to undergo pill training prior to enrollment * weight must be greater than or equal to 15kg
Exclusion criteria
* Unable to swallow pills * Concomitant treatment with Rifampin or St. John's Wort which have been shown to decrease plasma concentrations of lopinavir. * Concurrent use of drugs primarily metabolized by CYP3A, which metabolizes ritonavir: Astemizole, Cisapride, Dihydroergotamine, Ergonovine, Ergotamine, Flecainide, Lovastatin, Methylergonovine, Midazolam, Pimozide, Propafenone, Simvastatin, terfenadine, Triazolam * Baseline treatment does NOT include Kaletra
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lopinavir and Ritonavir AUC on Low Dose Tablet | 4 weeks | Lopinavir and Ritonavir AUC at 4 weeks when participants are receiving the study intervention, low dose tablet formulation of Kaletra. Data collection points for AUC were 0, 2, 4, 6, and 8 hours post dose. |
| Lopinavir AUC Ratio of Baseline:Week 4 | Baseline, week 4 | Ratio of AUC at baseline (liquid)to week 4 (reduced dose tablet). AUC data were collected at 0, 2, 4, 6, and 8 hours post dose. |
| Viral Load (VL) | Baseline, Week 4, Week 12 and Week 24 | Number of participants who maintained their Viral load undetectable (\< 20 copies/ml) for the duration of the study |
| Lopinavir (Lpv) and Ritonavir (Rtv) Cmax at 4 Weeks | 4 weeks | Lpv and rtv Cmax at 4 weeks when participants are receiving study intervention, low dose Kaletra. Time points for data collection: 0, 2hrs, 4hrs, 6hrs, 8hrs |
| Absolute CD4 and CD4 % | Baseline, 4 weeks, 12 weeks, 26 weeks | Number of participants who had no clinically significant deterioration in absolute CD4 and % CD4 count for the duration of the study. Absolute CD4 and Percent CD4 counts were determined by single or dual platform analysis performed on blood samples by Phoenix Children's Hospital Laboratory, Sonora Quest Laboratory or Labcorp Laboratory. Clinically significant change was determine to be a deterioration in both Absolute CD4 to less than 500 and %CD4 to less than 25%. |
| Lopinavir (Lpv) and Ritonavir (Rtv) Maximumu Plasma Concentration (CMax) Liquid | Baseline | Cmax values at baseline (participants are taking liquid Kaletra as part of baseline treatment). Time points for data collection: 0, 2hrs post dose, 4 hrs post dose, 8 hrs post dose. |
| Lopinavir and Ritonavir Area Under the Curve (AUC) Liquid Kaletra | Baseline | Area under the curve values for lopinavir at baseline when participants are taking liquid Kaletra as part of their baseline treatment. Time points for data collection: 0, 2 hrs post, 4 hrs post, 6 hrs post, 8 hrs post. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms Across All Patients | Baseline, 1 month, 3 months, 6 months | Cumulative tally of symptoms for each patients across all visits. Targetted symptoms were asked for at each visit and patients and parents were encouraged to report additional symptoms that were experienced. Each patient got a score for the total number of symptoms at each visit. Scores were totalled, but it the same symptoms occurred continuously it was counted as 1 symptom. |
| Parent Satisfaction | Baseline, 4 week, 12 weeks and 24 weeks | Parent Satisfaction Survey. Eight item Likert scale of parent/guardian satisfaction with the child's HIV treatment regimen. Item scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction. |
| Patient Satisfaction | Baseline, 1 month | Patient Satisfaction Survey. Eight item Likert scale of patient satisfaction with their HIV treatment regimen for patients 7 years of age and older. Items scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction. |
Countries
United States
Participant flow
Recruitment details
Patients weighing 15kg and able to swallow pills, currently taking liquid lpv/rtv were recruited from an outpatient pediatric HIV clinic from 4/1/2009 through 1/12/11
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Kaletra Patients will serve as their own controls as they are switched from liquid Kaletra to Low Dose Tablet Kaletra
Low dose Kaletra tablets : Lopinavir/Ritonavir tablets 100mg/25mg | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Low Dose Kaletra |
|---|---|
| Age, Categorical <=18 years | 8 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 7.18 years STANDARD_DEVIATION 1.79 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Absolute CD4 and CD4 %
Number of participants who had no clinically significant deterioration in absolute CD4 and % CD4 count for the duration of the study. Absolute CD4 and Percent CD4 counts were determined by single or dual platform analysis performed on blood samples by Phoenix Children's Hospital Laboratory, Sonora Quest Laboratory or Labcorp Laboratory. Clinically significant change was determine to be a deterioration in both Absolute CD4 to less than 500 and %CD4 to less than 25%.
Time frame: Baseline, 4 weeks, 12 weeks, 26 weeks
Population: All participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Kaletra | Absolute CD4 and CD4 % | 8 participants |
Primary
Lopinavir and Ritonavir Area Under the Curve (AUC) Liquid Kaletra
Area under the curve values for lopinavir at baseline when participants are taking liquid Kaletra as part of their baseline treatment. Time points for data collection: 0, 2 hrs post, 4 hrs post, 6 hrs post, 8 hrs post.
Time frame: Baseline
Population: All participants were analyzed
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Kaletra | Lopinavir and Ritonavir Area Under the Curve (AUC) Liquid Kaletra | Lpv AUC at baseline | 90651 hr*ng/ml | Standard Deviation 30346.4 |
| Low Dose Kaletra | Lopinavir and Ritonavir Area Under the Curve (AUC) Liquid Kaletra | Rtv AUC at baseline | 3701.2 hr*ng/ml | Standard Deviation 2088 |
Primary
Lopinavir and Ritonavir AUC on Low Dose Tablet
Lopinavir and Ritonavir AUC at 4 weeks when participants are receiving the study intervention, low dose tablet formulation of Kaletra. Data collection points for AUC were 0, 2, 4, 6, and 8 hours post dose.
Time frame: 4 weeks
Population: All participants were analyzed
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Kaletra | Lopinavir and Ritonavir AUC on Low Dose Tablet | Lpv AUC at 4 weeks | 85670 hr*ng/ml | Standard Deviation 25184.5 |
| Low Dose Kaletra | Lopinavir and Ritonavir AUC on Low Dose Tablet | Rtv AUC at 4 weeks | 4876.1 hr*ng/ml | Standard Deviation 2541 |
Primary
Lopinavir AUC Ratio of Baseline:Week 4
Ratio of AUC at baseline (liquid)to week 4 (reduced dose tablet). AUC data were collected at 0, 2, 4, 6, and 8 hours post dose.
Time frame: Baseline, week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Kaletra | Lopinavir AUC Ratio of Baseline:Week 4 | 1.01 ratio | Standard Deviation 0.36 |
Primary
Lopinavir (Lpv) and Ritonavir (Rtv) Cmax at 4 Weeks
Lpv and rtv Cmax at 4 weeks when participants are receiving study intervention, low dose Kaletra. Time points for data collection: 0, 2hrs, 4hrs, 6hrs, 8hrs
Time frame: 4 weeks
Population: All participants were analyzed
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Kaletra | Lopinavir (Lpv) and Ritonavir (Rtv) Cmax at 4 Weeks | Lpv Cmax at 4 weeks | 11143 ng/ml | Standard Deviation 2839.5 |
| Low Dose Kaletra | Lopinavir (Lpv) and Ritonavir (Rtv) Cmax at 4 Weeks | Rtv Cmax at 4 weeks | 912.1 ng/ml | Standard Deviation 588.9 |
Primary
Lopinavir (Lpv) and Ritonavir (Rtv) Maximumu Plasma Concentration (CMax) Liquid
Cmax values at baseline (participants are taking liquid Kaletra as part of baseline treatment). Time points for data collection: 0, 2hrs post dose, 4 hrs post dose, 8 hrs post dose.
Time frame: Baseline
Population: All participants were analyzed
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Kaletra | Lopinavir (Lpv) and Ritonavir (Rtv) Maximumu Plasma Concentration (CMax) Liquid | Cmax Lpv | 9742 ng/ml | Standard Deviation 2533.9 |
| Low Dose Kaletra | Lopinavir (Lpv) and Ritonavir (Rtv) Maximumu Plasma Concentration (CMax) Liquid | Cmax Rtv | 637.0 ng/ml | Standard Deviation 357.5 |
Primary
Viral Load (VL)
Number of participants who maintained their Viral load undetectable (\< 20 copies/ml) for the duration of the study
Time frame: Baseline, Week 4, Week 12 and Week 24
Population: All subjects in study were analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Kaletra | Viral Load (VL) | 8 participants |
Secondary
Parent Satisfaction
Parent Satisfaction Survey. Eight item Likert scale of parent/guardian satisfaction with the child's HIV treatment regimen. Item scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction.
Time frame: Baseline, 4 week, 12 weeks and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Kaletra | Parent Satisfaction | 26.75 Score on a survey | Standard Deviation 3.92 |
| Low Dose Kaletra Week 4 Visit | Parent Satisfaction | 28.38 Score on a survey | Standard Deviation 3.02 |
p-value: <0.001t-test, 2 sided
Secondary
Patient Satisfaction
Patient Satisfaction Survey. Eight item Likert scale of patient satisfaction with their HIV treatment regimen for patients 7 years of age and older. Items scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction.
Time frame: Baseline, 1 month
Population: Patients had to be able to read and write to complete the patient satisfaction questionnaire, so an arbitrary age of 7 was selected and patients under the age of 7 did not complete the patient satisfaction questionnaire. All 5 of the patients over the age of 5 completed the questionnaire and were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Kaletra | Patient Satisfaction | 20.2 units on a scale | Standard Deviation 7.76 |
| Low Dose Kaletra Week 4 Visit | Patient Satisfaction | 21.8 units on a scale | Standard Deviation 6.02 |
p-value: =0.004t-test, 2 sided
Secondary
Symptoms Across All Patients
Cumulative tally of symptoms for each patients across all visits. Targetted symptoms were asked for at each visit and patients and parents were encouraged to report additional symptoms that were experienced. Each patient got a score for the total number of symptoms at each visit. Scores were totalled, but it the same symptoms occurred continuously it was counted as 1 symptom.
Time frame: Baseline, 1 month, 3 months, 6 months
Population: All participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Kaletra | Symptoms Across All Patients | Symptoms for all subjects at Baseline | 20.20 numer of symptoms | Standard Deviation 7.76 |
| Low Dose Kaletra | Symptoms Across All Patients | Symptoms for all subjects at 4 Weeks | 21.80 numer of symptoms | Standard Deviation 6.02 |
| Low Dose Kaletra | Symptoms Across All Patients | Symptoms for all subjects at 12 Weeks | 26.40 numer of symptoms | Standard Deviation 2.3 |
| Low Dose Kaletra | Symptoms Across All Patients | Symptoms for all subjects at 24 weeks | 26.60 numer of symptoms | Standard Deviation 3.21 |