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
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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 |
(Concluded) | |
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Phase III Trial of Antibiotics to Reduce Chorioamnionitis-Related Perinatal HIV Transmission |
(Participants Off Study & Primary Analysis Complete) | |
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A Phase I Study to Evaluate the Safety and Immunogenicity of ALVAC-HIV vCP1521 in Infants Born to HIV-1 Infected Women in Uganda |
(Participants Off Study & Primary Analysis Complete) | |
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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 |
(Closed to Follow Up) | |
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A Phase I Open Label Trial of the Safety and Pharmacokinetics of Tenofovir Disoproxil Fumarate in HIV-1 Infected Pregnant Women and their Infants |
(Closed to Follow Up) |
