Perinatal
Science Research Strategy
Overview
The HPTN's perinatal agenda is
transitioning to the
International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT).
Information on current HPTN perinatal trials will be maintained on the HPTN
website until this transition process is complete.
 Successful interventions in the antepartum,
intrapartum, and postpartum periods to prevent transmission from an
HIV-infected woman to her infant have already been identified and
implemented, but there are more opportunities yet to be pursued.
Of the highest importance are safe, simple, inexpensive
interventions that could be widely applicable, particularly in the
developing world.
Antepartum
Now that the efficacy of antiretroviral (ARV) agents to reduce
mother-to-child transmission (MTCT) during the antepartum period has been
established, studies of non-antiretroviral or improved antiretroviral
regimens must be compared with proven regimens.
As a result, the ability to discern an effect from a new
intervention requires a significantly increased study size to detect a
difference. In
HIVNET
024, antibiotics given antenatally and at delivery to reduce
chorioamnionitis-related HIV infection showed no added protection against
MTCT of HIV beyond that conferred by the
HIVNET 012 regimen.
Considerations
for antepartum interventions include new ARV agents and regimens, other
mechanisms to further reduce maternal viral load, and immunomodulators.
Intrapartum/Neonatal
As
shown in HIVNET 012, an intrapartum/neonatal regimen consisting of a
single 200 mg dose of nevirapine (NVP) given to the mother at the onset of
labor and a single 2 mg/kg dose of NVP given to the infant within 72 hours
of life reduced the risk of perinatal transmission among breastfeeding
women in Uganda by 47% at 14-16 weeks and by 41% at 18 months compared to
an intrapartum/neonatal regimen of AZT (600 mg, then 300 mg every 3 hours
during labor to mother, and 4mg/kg twice daily for one week to the
infant). This regimen has been
adopted as the standard of care by the Ministries of Health in many
resource-limited countries. However,
inadequate infrastructure has limited widespread implementation.
There
is concern that use of the single-dose NVP regimen will induce resistance
that might diminish the utility of NVP or other NNRTIs if they become
available for use as treatment in a combination antiretroviral regimen.
In HIVNET 012, resistant virus had faded from detection by 12
months postpartum. It will be
important to assess the response to NVP therapy and repeat single-dose NVP
prophylaxis in women and children who have been exposed to the single-dose
NVP regimen.
Postpartum
Safe alternatives to breastfeeding are limited or infeasible in resource
poor settings, where the majority of HIV infected women reside, and the
benefits of breastfeeding are well known. Therefore,
an intervention to reduce the risk of HIV-1 transmission during
breastfeeding would be of utmost benefit to women and children in resource
limited settings and is among the highest priorities for the HPTN PSWG.
The impact of successful antepartum, intrapartum and/or neonatal
regimens of ARV may be diminished in breastfeeding populations with
continual exposure to breastmilk. Several
important studies by the HPTN and other groups are underway or planned to
examine the safety and efficacy of various ARV regimens given for
different durations during breastfeeding (e.g.
HPTN 046), most in
combination with an antepartum and/or intrapartum component.
However, the potential high cost and difficult logistics of
continuing ARV therapy in the infant or mother for the duration of
breast-feeding may prohibit widespread and routine use in many resource
poor countries. Therefore, active
and passive immunization strategies, perhaps combined with antepartum
and/or intrapartum ARV regimens pose an attractive and important
alternative. Testing
of appropriate HIV-1-specific antibody products and candidate HIV-1
vaccines as they become available is critical.
HPTN Perinatal Studies
|
HIVNET 012 |
A Phase IIB Trial to Determine the Efficacy of Oral AZT and the Efficacy of Oral Nevirapine for the Prevention of Vertical Transmission of HIV-1 Infection in Pregnant Ugandan Women and Their Neonates |
(Closed to Follow Up) |
|
HIVNET 024 |
Phase III Trial of Antibiotics to Reduce Chorioamnionitis-Related Perinatal HIV Transmission |
(Participants Off Study & Primary Analysis Complete) |
|
HPTN 027 |
A Phase I Study to Evaluate the Safety and Immunogenicity of ALVAC-HIV vCP1521 in Infants Born to HIV-1 Infected Women in Uganda |
(Closed to Accrual) |
|
HPTN 046 |
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 |
(Enrolling) |
|
HPTN 057 |
A Phase I Open Label Trial of the Safety and Pharmacokinetics of Tenofovir Disoproxil Fumarate in HIV-1 Infected Pregnant Women and their Infants |
(Enrolling) |
|
