Phase III Trial to Determine the Efficacy and Safety of an Extended Regimen of Nevirapine in Infants Born to HIV Infected Women to Prevent Vertical HIV Transmission During Breastfeeding
What is HPTN 046?
In 2006, an estimated 530,000 children became infected with HIV, mainly in developing countries. Since the beginning of the HIV epidemic, an estimated 2.3 million children worldwide have been infected with HIV. Mother to child HIV transmission (MTCT) is responsible for more than 90% of these infections, in which HIV is transmitted during pregnancy, labor, delivery, or during breastfeeding. Among infected infants who are not breastfed, about two-thirds of the cases of MTCT occur around the time of delivery and the rest during pregnancy (mostly during the last 2 months). In populations where breastfeeding is the norm, postnatal transmission through breast milk accounts for more than one-third of all transmission. Therefore, even though antepartum and intrapartum antiretroviral regimens have been shown to significantly reduce MTCT, these substantial gains may be lost in breastfeeding populations in which infants have continued exposure to HIV through breast milk. It is, therefore, the goal of HPTN 046 to evaluate an intervention that may enable HIV-infected mothers who wish to breastfeed, or who have no other option, to do so while still protecting their infants from HIV infection.
Protocol Status: Participants Off Study & Primary Analysis Complete
Study Purpose: To evaluate the efficacy and safety of an extended regimen of nevirapine (NVP) from 6 weeks to 6 months or through cessation of breastfeeding, whichever is earliest, for prevention of mother-to-child transmission of HIV through breast milk compared with placebo among infants who are provided nevirapine for the first 6 weeks (through Day 42) of life and are HIV-uninfected at age 6 weeks.
Study Design: Phase III, multi-site, randomized, double-blind, placebo controlled trial. Stratification: Randomization will be stratified by maternal antiretroviral therapy with two levels based on maternal therapy for treatment of HIV at the point of randomization: mothers receiving antiretroviral therapy (ART) or mothers not receiving antiretroviral therapy (ART).
Study Population: HIV-1 infected women and their breastfeeding infants.
Study Size: Approximately 1670 mother/infant pairs will need to be enrolled at birth (within 7 days) in order to randomize the target of 1500 infants at six weeks. In addition, approximately 350 mother/infant pairs originally enrolled under Version 2.0 of the protocol will be followed under Version 3.0.
Study Duration: Total duration of the study will be approximately 3.5 years. Participants will be enrolled over a period of approximately 18 to 24 months; randomized mothers and infants will be maintained in follow-up through 18 months postpartum.
Treatment Regimen: Infants eligible under Version 3.0 of the protocol will be enrolled in the study on or before day 7 after birth: All infants will receive a daily regimen of open-label NVP through 6 weeks (42 days) of life starting at 3 to 7 days after birth. Infants still eligible at 6 weeks of age will be randomized to one of two study arms and will initiate the daily study drug regimen (NVP or NVP placebo). Infants enrolled under Version 2.0 of the protocol: Infants either randomized to the placebo arm and over 6 weeks (> or = to 43 days) of age as of 10 August 2007 or randomized to the NVP arm (regardless of age) will continue the dosing regimen to which they were randomized according to the age-appropriate dose. Infants who were not randomized (including those enrolled on or after 10 August 2007) or who were randomized to the placebo arm of the study and were under 6 weeks (< 43 days) of age as of10 August 2007 will be provided open-label NVP through six weeks (42 days) of life.
Primary Objectives: Compare the rate of HIV-1 infection at 6 months in infants determined to be HIV uninfected at 6 weeks in each arm Evaluate and compare the safety and tolerance in infants in each arm
Secondary Objectives: Compare the proportion of infants who are alive and free of HIV at 6 months and 18 months of age in the two arms. Compare the relative rates of HIV infection in infants over 18 months in the two arms. Compare the infant survival rates (mortality regardless of HIV infection) over 18 months in the two arms. Determine the frequency and duration of NVP-resistant HIV strains in maternal plasma and breast milk and the relationship with MTCT. Determine the relationship of maternal plasma and breast milk RNA levels to risk of MTCT. Determine the frequency, type, and duration of NVP-resistant HIV strains in the plasma of infants who become HIV-infected. Compare the rates of HIV disease progression, as defined by CD4+ cell count, HIV-1 RNA copy number, and mortality between the two arms in infants who become HIV-infected. Determine NVP concentrations in infants who become infected with HIV and a sample of HIV uninfected infants as an index of adherence to the NVP regimen.
SDMC Protocol Specialist: get info
Protocol Co-Chair: Dhayendre Moodley get info
Protocol Co-Chair: Laura A. Guay get info
Protocol Co-Chair: Wafaie Fawzi get info
Protocol Co-Chair: Yvonne A. Maldonado get info
Protocol Chair: Hoosen Coovadia get info
DAIDS Medical Officer: Lynne Mofenson get info
DAIDS Medical Officer: Sheryl Zwerski get info
CORE Protocol Specialist: Kathleen George get info
CORE Protocol Specialist: Philip Andrew get info