Clinical trial NCT03033368: Rilpivirine in Virologically Suppressed Adolescents
Official title: Treatment Switch From Efavirenz to Rilpivirine in Virologically-suppressed HIV-infected Thai Adolescents
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: HIV
Keywords: immunological outcome
virologic outcomes
HIV-1 infected adolescents
EFV switch to RPV
Rilpivirine pharmacokinetic
neuropsychiatric adverse events
Lead sponsor: Mahidol University
Sponsor class: OTHER
Collaborators: name: amfAR, The Foundation for AIDS Research
First posted: 2017-01-26
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To describe the immunologic and virologic outcomes (HIV RNA, CD4) following switching from EFV to RPV in virologically suppressed adolescents

Detailed description: Study Procedures:

At screening, the informed consent process will be provided to participant, or participant legally acceptable representatives before any study procedure. Only adolescents who know their HIV status will be asked to give assent.

Twenty adolescents followed at HIV-NAT and the Department of Pediatrics, Faculty of Medicine, Chulalongkorn University will be asked to participate in the PK sub study. Participant who are enrolled in the PK substudy will be asked to take RPV in the morning after breakfast and then commence the PK evaluations after this witnessed dose. After the PK study at week 4, Participant will be followed with the other 80 adolescents until the end of the study. Participant will be asked to provide a small hair sample for RPV concentrations at weeks 4, 12, 24, and 48 after switching. This is an option therefore participant can refuse to provide their hair samples at any visits. HIV RNA levels will be performed at baseline, week 12, 24 and 48 visits. If the HIV-RNA at any visits is between \>50 copies/ml, the HIV-RNA test will be repeated within 4-8 weeks with adherence improvement counseling. At any visit, if HIV-RNA is ≥1000 copies/ml, genotypic resistance testing will be performed. Modification of treatment both for resistance and safety consideration will be subject to the site principal investigator's decision.

Eligibility criteria: Inclusion Criteria:

* HIV-infected adolescents aged 12-18 years;
* Body weight \>25 kilograms;
* Currently treated with stable EFV-based HAART (EFV plus two nucleoside or nucleotide reverse transcriptase inhibitors \[N(t)RTI\]) for \>3 months prior to enrollment;
* Plasma HIV RNA \<50 copies/ml within the last 12 months;
* ALT \<200 IU/L within the last 12 months;
* Caregivers give written informed consent and adolescents who know their HIV status (i.e., have been fully disclosed to) give assent

Exclusion Criteria:

* Has evidence of NNRTI-associated resistance mutation(s) from previous genotypic resistance testing;
* Currently has PI(s) in the HAART regimen;
* Has currently active HIV-related infection(s), (The subject can be enrolled after the infection is under controlled);
* Has significant medical problem(s) that would compromise study results (in the site principal investigator's opinion);
* Pregnancy (postpartum women are allowed);
* Concomitant treatment with drugs known to effect the PK of RPV (carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin, omeprazole, esomeprazole, lansoprazole, erythromycin, clarithromycin, azithromycin, roxithromycin)

Primary outcomes:
measure: Proportion of adolescents with HIV-RNA <50 copies/ml at 48 weeks after switching.
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in neuropsychiatric test scores
timeFrame: Baseline and week 24
measure: Change in quality of life (QOL) score
timeFrame: Baseline, week 4 and week 24
measure: Change in lipid profiles after switching to RPV-containing regimens
timeFrame: Baseline, week 24, and week 48
measure: Change in fasting blood sugar after switching to RPV-containing regime
timeFrame: Baseline, week 24, and week 48
measure: Intensive PK parameter (Area under the plasma concentration-time curve; AUC0-24) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
timeFrame: week 4
measure: Intensive PK parameter (maximum observed concentration of drug in plasma ;(Cmax) ) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
timeFrame: week 4
measure: Intensive PK parameter (Minimum concentration of drug in plasma; (Ctrough)) of RPV in 20 subjects at 4 weeks after switching to RPV-containing regimens.
timeFrame: week 4
measure: Description of resistance mutations in the adolescents with RPV treatment failure
timeFrame: baseline, week 12, week 24 and week 48
Other outcomes:
Locations:
Study officials:
References:
citation: Jantarabenjakul W, Anugulruengkitt S, Kasipong N, Thammajaruk N, Sophonphan J, Bunupuradah T, Cressey TR, Colbers A, Burger DM, Phongsamart W, Puthanakit T, Pancharoen C; HIVNAT 220 study. Pharmacokinetics of rilpivirine and 24-week outcomes after switching from efavirenz in virologically suppressed HIV-1-infected adolescents. Antivir Ther. 2018;23(3):259-265. doi: 10.3851/IMP3198.