Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
The purpose of this study is to determine whether the current dose of nevirapine recommended in the Ontario Ministry of Health vertical transmission prevention protocol achieves therapeutic drug levels in newborn infants at high risk of HIV infection.
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection|
- Proportion of nevirapine trough (Cmin) plasma levels that are above or below the target range for prophylaxis [ Time Frame: Weeks 1, 2, and 4 ] [ Designated as safety issue: No ]
- Final dose of nevirapine [ Time Frame: Week 4 ] [ Designated as safety issue: No ]Final dose of nevirapine required to achieve target plasma trough concentrations at week 4
- Derived pharmacokinetic parameters [ Time Frame: Week 4 ] [ Designated as safety issue: No ]Derived pharmacokinetic parameters volume of distribution (Vd)(L/kg), elimination rate (ke), clearance (mL/kg/hr), Cmin (ug/L), Cmax (ug/L), Tmax (hrs), and Area under the Curve (AUC)
- Association between nevirapine levels and incidence of adverse effects [ Time Frame: Weeks 1, 2 and 4 ] [ Designated as safety issue: Yes ]Number of adverse events among patients with therapeutic vs. supratherapeutic nevirapine levels
- Association between patient characteristics and differences in nevirapine levels [ Time Frame: Baseline, Week 1, 2 and 4 ] [ Designated as safety issue: No ]Patient characteristics that may explain differences in nevirapine levels including chronologic and gestational age, weight, and ethnic background.
- Rate of vertical transmission of HIV [ Time Frame: 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission.
Although nevirapine (NVP) is often given as part of combination antiretroviral therapy (cART) at our institutions for prevention of vertical transmission (VT) in high risk infants, the optimal prophylactic dose of nevirapine is unknown. The National Institute of Health (NIH) guidelines currently recommend a single 2 mg/kg dose of nevirapine given to the infant within 72 hours of birth, however, this dose is not being used in practice given the controversies previously described with single-dose nevirapine. In the absence of any guidance to inform the multiple daily dosing of nevirapine for prophylaxis of VT, we are currently using the treatment dose for infants >15 days of age of 150 mg/m2 once daily for 14 days, then increasing to 150 mg/m2 twice daily for 14 days. This is analogous to the treatment dosing of triple antiretrovirals (ARVs) that is given for occupational post-exposure prophylaxis. Nevirapine is given for 4 weeks total with zidovudine (AZT) and lamivudine (3TC), followed by 2 additional weeks of AZT and 3TC to prevent the development of nevirapine resistance from its long half life. Stopping all 3 drugs simultaneously would result in a period of functional NVP monotherapy, resulting in a risk of NVP resistance should the infant become infected despite prophylaxis. Since the dose of nevirapine being used in our clinic populations for prevention of VT is higher than has been previously studied in neonates, it is important to evaluate the safety and efficacy of this dosing regimen, using therapeutic drug monitoring.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02166502
|Contact: Ari Bitnun, MD||416-813-7654 ext firstname.lastname@example.org|
|Contact: Elaine Lau, PharmDemail@example.com|
|Children's Hospital of Eastern Ontario||Recruiting|
|Ottawa, Ontario, Canada|
|Contact: Jason Brophy, MD|
|The Hospital for Sick Children||Recruiting|
|Toronto, Ontario, Canada, M5G1X8|
|Contact: Ari Bitnun, MD 416-813-7654 ext 204649 firstname.lastname@example.org|
|Contact: Elaine Lau, PharmD 416-813-6003 email@example.com|
|Principal Investigator: Ari Bitnun, MD, MSc|
|Sub-Investigator: Elaine Lau, PharmD, MSc|
|Principal Investigator:||Ari Bitnun, MD||The Hospital for Sick Children|