Clinical trial NCT02166502: Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
Official title: Nevirapine Dosing in Neonates for Prophylaxis of Mother-to-Child-Transmission (MTCT) of HIV Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Human Immunodeficiency Virus
HIV
Vertical Infection Transmission
Keywords: pediatric
HIV
prevention
prophylaxis
nevirapine
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Foundation for AIDS Research (CANFAR)
name: Children's Hospital of Eastern Ontario
name: Unity Health Toronto
name: Mount Sinai Hospital, Canada
First posted: 2014-06-18
Enrollment: 27
Sex: ALL
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients in this study are newborn infants clinically prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. These infants are routinely referred to the SickKids and CHEO HIV clinics in Toronto and Ottawa, respectively, for ongoing management. The majority of referrals are from Mount Sinai Hospital and St. Michael's Hospital in Toronto, and the Ottawa General Hospital in Ottawa.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Newborn infants prescribed combination antiretroviral treatment with nevirapine for prevention of mother-to-child HIV transmission. These infants are routinely referred to the Hospital for Sick Children (SickKids) and Children's Hospital of Eastern Ontario (CHEO) HIV clinics in Toronto and Ottawa, respectively, for ongoing management. The majority of referrals are from Mount Sinai Hospital and St. Michael's Hospital in Toronto, and the Ottawa General Hospital in Ottawa.
* Voluntary informed consent by the legal guardian

Exclusion Criteria:

* Infants born prior to 32 weeks gestational age;
* Infants with life-threatening medical conditions;
* Infants unable to take oral medication;
* Infants born to women considered at high risk of harboring nevirapine resistance mutations in whom Kaletra (lopinavir/ritonavir) is a therapeutic option (e.g. term neonates) will be excluded and prescribed Kaletra rather than nevirapine

Primary outcomes:
measure: Proportion of nevirapine trough (Cmin) plasma levels that are above or below the target range for prophylaxis
timeFrame: Weeks 1, 2, and 4
Secondary outcomes:
measure: Final dose of nevirapine
timeFrame: Week 4
measure: Derived pharmacokinetic parameters
timeFrame: Week 4
measure: Association between nevirapine levels and incidence of adverse effects
timeFrame: Weeks 1, 2 and 4
measure: Association between patient characteristics and differences in nevirapine levels
timeFrame: Baseline, Week 1, 2 and 4
measure: Rate of vertical transmission of HIV
timeFrame: 18 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Ari Bitnun, MD
role: PRINCIPAL_INVESTIGATOR
References: