HIV Infections, Pediatric HIV
Conditions
Keywords
HIV, Lipids, Atazanavir, Pediatric, treatment experienced
Brief summary
The hypothesis for this study is whether a treatment regimen containing Atazanavir in combination with Ritonavir will work as well as other regimens containing a protease inhibitor and/or a Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) at controlling HIV disease in children who are HIV+ and have high cholesterol or high triglycerides. . In this study, children who have high cholesterol or high triglycerides as a result of their HIV medicines, will have the PI or NNRTI in their medication regimen changed to Atazanavir, which is a PI in combination with a low dose of Ritonavir (another PI). Atazanavir has been shown in adults to result in lower cholesterol and triglycerides than other PI's and NNRTI's. The dose of Atazanavir and Ritonavir will be according to the Package Insert for this drug that is FDA approved for children. They will continue taking the other medications from the pre-study regimen. Children will take study drug for 24 weeks, and will be able to continue study drug after the study using commercially available drug. Lab tests and a physical exam will be undertaken at 4 weeks, 12 weeks and 24 weeks after starting study drug to determine how effective the new drug is and to monitor for possible side effects.
Detailed description
The primary objective of this study is to determine if Atazanavir and Ritonavir together will be as effective as the child's previous regimen in keeping the level of virus in the blood stream at such a low level it can't be found and whether that combination will be as effective as the previous regimen in keeping the infection fighting cells in the blood at the same level. Secondary objectives will be: * To determine if cholesterol and triglyceride levels drop in children switching to Atazanavir and Ritonavir from other medication regimens. * To evaluate if Atazanavir and Ritonavir result in an increase in patient satisfaction and patient reported adherence and a decrease in symptoms related to medication side effects. Inclusion Criteria are: * On the same medication regimen at least 3 months * Weight equal to or greater than 25kg * Able to swallow pills or willing to learn * Have a parent or guardian willing and able to sign informed consent * Not be taking a medication which interacts with Atazanavir * Not be currently taking Sustiva
Interventions
Boosted Atazanavir, once a day dose adjusted for child's weight for 6 months.
Sponsors
Bristol-Myers Squibb
Phoenix Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* HIV positive children with elevated lipid levels * on stable HAART for at least 3 months (defined to be on the same regimen with viral load \< 1000 for 6 months prior to baseline visit). * Weight equal to or greater than 25kg * Able to swallow pills or willing to learn
Exclusion criteria
* Patients with underlying hepatitis B or C viral infections * Previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of Reyataz® (atazanavir). * Taking other medications that are highly dependent on CYP3A or UGT1A1 for clearance * Ergot medicines: dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as Cafergot®, Migranal®, D.H.E. 45®, ergotrate maleate, Methergine®, and others (used for migraine headaches). * Orap® (pimozide, used for Tourette's disorder). * Propulsid® (cisapride, used for certain stomach problems). * Triazolam, also known as Halcion® (used for insomnia). * Midazolam, also known as Versed® (used for sedation), when taken by mouth. * Camptosar® (irinotecan, used for cancer). * Crixivan® (indinavir, used for HIV infection). * Cholesterol-lowering medicines Mevacor® (lovastatin) or Zocor® (simvastatin). * Rifampin (also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®). * St. John's wort (Hypericum perforatum), an herbal product sold as a dietary supplement, * Viramune® (nevirapine, used for HIV infection). * Vfend® (voriconazole). * Patients with grade 3 or higher elevations in transaminases (\> 10 X ULN) * Women of Childbearing Potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period. * Women who are pregnant or breastfeeding. * Women with a positive pregnancy test.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Non-fasting Cholesterol | 4 Weeks, 12 weeks, 24 weeks |
| Non-fasting Triglycerides | 4 weeks, 12 weeks, 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Load | 4 weeks, 12 weeks, 24 weeks | Number of participants with undetectable viral load |
| CD4 Count | 4 Weeks, 12 weeks, 24 weeks | — |
Countries
United States
Participant flow
Recruitment details
Pediatric patients with elevated cholesterol were recruited from a Pediatric HIV Clinic between April 8, 2009 and May 1, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Boosted Atazanavir Boosted atazanavir was switched for the PI or NNRTI in the patients regimen
Boosted Atazanavir: Boosted atazanavir, once a day dose adjusted for child's weight for 6 months. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Boosted Atazanavir |
|---|---|
| Age, Continuous | 9.5 years |
| CD4 | 1233.1 cells/uL STANDARD_DEVIATION 473.8 |
| Cholesterol | 214.3 mg/dL STANDARD_DEVIATION 31.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
| Triglycerides | 288.5 mg/dL STANDARD_DEVIATION 253.9 |
| Viral Load | 2.3 copies/ml STANDARD_DEVIATION 7.3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Non-fasting Cholesterol
Time frame: 4 Weeks, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Boosted Atazanavir | Non-fasting Cholesterol | Week 4 | 187.2 mg/dL | Standard Deviation 30 |
| Boosted Atazanavir | Non-fasting Cholesterol | Week 12 | 178.5 mg/dL | Standard Deviation 38.1 |
| Boosted Atazanavir | Non-fasting Cholesterol | Week 24 | 181.5 mg/dL | Standard Deviation 29.3 |
p-value: 0.006Friedman's Test
Comparison: Nul lHypothesis that there is no difference between specific time points.p-value: 0.007Wilcoxon Signed Rank
Primary
Non-fasting Triglycerides
Time frame: 4 weeks, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Boosted Atazanavir | Non-fasting Triglycerides | Week 4 | 240.5 mg/dL | Standard Deviation 107.2 |
| Boosted Atazanavir | Non-fasting Triglycerides | Week 12 | 195.5 mg/dL | Standard Deviation 93.8 |
| Boosted Atazanavir | Non-fasting Triglycerides | Week 24 | 193.3 mg/dL | Standard Deviation 106.5 |
p-value: 0.356Friedman's Test
Secondary
CD4 Count
Time frame: 4 Weeks, 12 weeks, 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Boosted Atazanavir | CD4 Count | Week 4 | 1214.3 cells/uL | Standard Deviation 476.8 |
| Boosted Atazanavir | CD4 Count | Week 12 | 1151.9 cells/uL | Standard Deviation 442.7 |
| Boosted Atazanavir | CD4 Count | Week 24 | 1120.0 cells/uL | Standard Deviation 413.2 |
p-value: 0.075Friedman's test
Secondary
Viral Load
Number of participants with undetectable viral load
Time frame: 4 weeks, 12 weeks, 24 weeks
Population: Number of patients with undetectable viral load
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boosted Atazanavir | Viral Load | Week 4 | 10 Participants |
| Boosted Atazanavir | Viral Load | Week 12 | 9 Participants |
| Boosted Atazanavir | Viral Load | Week 24 | 9 Participants |
Comparison: The null hypothesis was that there was a difference. We were looking for no difference between before and after switch.p-value: 0.801Friedman's test