Perinatal Science

Overview

The HPTN's perinatal research agenda has transitioned to the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network.  The information provided below describes the research that was conducted by the HPTN prior to that transition.

Antepartum

After the efficacy of antiretroviral (ARV) agents to reduce mother-to-child transmission (MTCT) during the antepartum period was established, studies of non-antiretroviral or improved antiretroviral regimens needed to be compared with proven regimens in a significantly large enough study size to detect efficacy. In HIVNET 024, antibiotics given antenatally and at delivery to reduce chorioamnionitis-related HIV infection showed no added protection against mother-to-child-transmision (MTCT) of HIV beyond that conferred by the HIVNET 012 regimen.

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 was adopted as the standard of care by the Ministries of Health in many resource-limited countries.  However, inadequate infrastructure limited widespread implementation. 
 
There was 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 was therefore considered to 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 was among the highest research priorities. 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 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