Maternal humoral immune responses do not predict postnatal HIV-1 transmission risk in antiretroviral-treated mothers from the IMPAACT PROMISE Study

mSphere, Volume 4, No. 5, Year 2019

Interpretation

To design immune interventions that can synergize with antiretroviral therapy (ART) to reduce the rate of HIV mother-to-child transmission (MTCT), it is essential to characterize maternal immune responses in the setting of ART during pregnancy and breastfeeding and define their effect on MTCT. Prior studies reported an association between breast milk envelope (Env)-specific antibodies and antibodydependent cell cytotoxicity (ADCC) activity with reduced postnatal transmission. In this study, we investigated whether these immune correlates were similarly associated with protection in a matched case-control study of mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding in the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial, assessing postnatal transmission risk in 19 transmitting and 57 nontransmitting mothers using conditional logistic regression models adjusted for maternal plasma viral load. The odds ratios of postnatal MTCT for a 1-unit increase in an immune correlate were 3.61 (95% confidence interval [CI], 0.56, 23.14) for breast milk Env-specific secretory IgA (sIgA), 2.32 (95% CI, 0.43, 12.56) for breast milk and 2.16 (95% CI, 0.51, 9.14) for plasma Env-specific IgA, and 4.57 (95% CI, 0.68, 30.48) for breast milk and 0.96 (95% CI, 0.25, 3.67) for plasma ADCC activity, with all CIs spanning 1.0. Interestingly, although mucosal IgA responses are poor in untreated HIV-infected women, there was a strong correlation between the magnitudes of breast milk and plasma Env-specific IgA in this cohort. In this analysis of the small number of postnatal virus transmissions in the landmark PROMISE study, no single antibody response was associated with breast milk transmission risk. IMPORTANCE Each year, 150,000 infants become newly infected with HIV-1 through MTCT despite ART, with up to 42% of infections occurring during breastfeeding. Several factors contribute to continued pediatric infections, including ART nonadherence, the emergence of drug-resistant HIV strains, acute infection during breastfeeding, and poor access to ART in resource-limited areas. A better understanding of the maternal humoral immune responses that provide protection against postnatal transmission in the setting of ART is critical to guide the design of maternal vaccine strategies to further eliminate postnatal HIV transmission. In this study, we found that in women treated with antiretrovirals during pregnancy, there was a positive correlation between plasma viral load and breast milk and plasma IgA responses; however, conclusions regarding odds of MTCT risk were limited by the small sample size. These findings will inform future studies to investigate maternal immune interventions that can synergize with ART to eliminate MTCT during breastfeeding.

AI Digest

Study Justification:

– The study aims to characterize maternal immune responses in the context of antiretroviral therapy (ART) during pregnancy and breastfeeding.
– Understanding these immune responses is crucial for designing interventions to reduce the rate of HIV mother-to-child transmission (MTCT).
– Previous studies have shown an association between specific antibodies and reduced postnatal transmission, but more research is needed to confirm these findings.

Study Highlights:

– The study analyzed data from the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Network Promoting Maternal-Infant Survival Everywhere (PROMISE) trial.
– It focused on mother-infant pairs receiving maternal ART or infant nevirapine prophylaxis during breastfeeding.
– The study investigated whether specific immune responses were associated with protection against postnatal transmission.
– The odds ratios for postnatal MTCT were calculated for different immune correlates, such as breast milk envelope-specific secretory IgA (sIgA) and plasma envelope-specific IgA.
– The study found no single antibody response that was associated with breast milk transmission risk.

Recommendations for Lay Reader and Policy Maker:

– The study highlights the need for further research to understand maternal immune responses in the context of ART during pregnancy and breastfeeding.
– These findings suggest that specific antibody responses may not be reliable predictors of postnatal transmission risk.
– The study emphasizes the importance of developing maternal vaccine strategies to eliminate postnatal HIV transmission.
– Future studies should investigate maternal immune interventions that can work in synergy with ART to prevent MTCT during breastfeeding.

Key Role Players:

– Researchers and scientists specializing in HIV/AIDS and maternal-infant health.
– Healthcare providers and clinicians involved in the care of HIV-positive pregnant women and their infants.
– Policy makers and government officials responsible for implementing and funding HIV prevention and treatment programs.
– Community organizations and advocates working to improve access to ART and support for HIV-positive mothers and their infants.

Cost Items for Planning Recommendations:

– Research funding for conducting further studies on maternal immune responses and developing maternal vaccine strategies.
– Resources for training healthcare providers on best practices for preventing MTCT during breastfeeding.
– Funding for HIV prevention and treatment programs, including access to ART for pregnant women and their infants.
– Support services for HIV-positive mothers and their families, such as counseling, education, and community outreach programs.

Strength of Evidence

The strength of evidence for this abstract is 6 out of 10.
The evidence in the abstract is rated 6 because it presents findings from a matched case-control study, but the sample size is small, limiting the conclusions that can be drawn. To improve the evidence, future studies should aim to include a larger sample size to increase statistical power and provide more robust results.

Abstract

Materials

N/A

Innovations

Based on the provided description, it appears that the study focused on investigating maternal immune responses and their effect on mother-to-child transmission (MTCT) of HIV-1 during pregnancy and breastfeeding. The study aimed to identify immune correlates that could potentially be targeted to reduce the risk of postnatal transmission. However, the study did not find a single antibody response that was associated with breast milk transmission risk.

Based on this information, here are some potential recommendations for innovations to improve access to maternal health:

1. Development of targeted maternal vaccines: Further research can be conducted to develop vaccines that specifically target maternal immune responses associated with reducing postnatal transmission of HIV-1. These vaccines could be administered during pregnancy to enhance the protective immune response in mothers.

2. Improved ART adherence strategies: Since nonadherence to antiretroviral therapy (ART) can contribute to continued pediatric infections, innovative strategies can be developed to improve ART adherence among pregnant women. This could include the use of mobile health technologies, reminder systems, or community-based support programs.

3. Expansion of access to ART in resource-limited areas: Efforts should be made to improve access to ART in resource-limited areas where poor access is a contributing factor to continued pediatric infections. This could involve strengthening healthcare infrastructure, increasing the availability of ART medications, and providing training and support to healthcare providers.

4. Integration of maternal health services: Maternal health services, including HIV prevention and treatment, should be integrated into existing healthcare systems to ensure comprehensive care for pregnant women. This can help improve access to necessary interventions and support for both maternal and child health.

5. Scaling up of breastfeeding support programs: Breastfeeding plays a crucial role in infant health, but it can also pose a risk of postnatal transmission. Scaling up breastfeeding support programs that provide education, counseling, and monitoring can help mothers make informed decisions about breastfeeding and reduce the risk of transmission.

It is important to note that these recommendations are based on the general understanding of the topic and may require further research and evaluation to determine their feasibility and effectiveness.

AI Innovations Description

Based on the provided description, the recommendation to improve access to maternal health and reduce the risk of HIV mother-to-child transmission (MTCT) during breastfeeding is to conduct further studies to investigate maternal immune interventions that can work in synergy with antiretroviral therapy (ART) to eliminate MTCT.

The study mentioned in the description found that there was a positive correlation between plasma viral load and breast milk and plasma IgA responses in women treated with antiretrovirals during pregnancy. However, the small sample size limited the conclusions regarding the odds of MTCT risk.

To address this issue and develop innovative solutions, it is recommended to:

1. Conduct larger-scale studies: Expand the sample size to obtain more robust data and draw more conclusive results. This will provide a better understanding of the maternal humoral immune responses and their impact on postnatal transmission risk.

2. Explore immune interventions: Investigate and develop interventions that can enhance the immune response in mothers receiving ART. This could involve designing maternal vaccine strategies or other interventions that can synergize with ART to further reduce the risk of MTCT during breastfeeding.

3. Improve access to ART: Address the challenges related to ART nonadherence and limited access to ART in resource-limited areas. This could involve implementing strategies to ensure consistent and effective ART usage among pregnant and breastfeeding women, such as improving healthcare infrastructure, providing education and support, and addressing barriers to access.

By implementing these recommendations, it is hoped that access to maternal health will be improved, and the rate of HIV MTCT during breastfeeding will be significantly reduced.

Authors & Co-Authors

Statistics:

Citations: 3

Authors: 15

Identifiers:

DOI: 10.1128/MSPHERE.00716-19

Research Areas:

Community Interventions, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Sexual and Reproductive Health

Study Design:

Case-Control Study, Cohort Study

Participants Gender:

Female