Combined antiretroviral therapy has significantly reduced perinatal human immunodeficiency virus (HIV) transmission risk through breastfeeding, prompting shifts in clinical guidance to support breastfeeding for women with HIV who have sustained viral suppression. This review examines the current evidence on HIV transmission via breast milk, including risk factors, mechanisms, and risk reduction strategies to inform patient-centered and evidence-driven clinical care.

Despite advances in human immunodeficiency virus (HIV) prevention, new pediatric HIV infections continue, necessitating optimized and simplified antiretroviral treatment (ART) regimens tailored for children. Advances in treatment options have been made possible by the availability of child-friendly fixed-dose formulations with decreased dosing frequency, especially in low- and middle-income countries. Ongoing work to improve ART options for neonates and supporting the shift toward long-acting ART for children and adolescents remains a priority. Achieving the UNAIDS goal of 95:95:95 for children will require a comprehensive and holistic approach that addresses both the biomedical and social challenges of managing children with HIV.

In 2023, US guidelines for feeding perinatally human immunodeficiency virus (HIV)-exposed infants were revised to encourage collaborative decision-making in lieu of categorical proscription of breastfeeding. This change advances autonomy and health equity for persons living with HIV in the United States, for the first time supporting those who prioritize the maternal and infant benefits of breastfeeding in the setting of effective, well-established HIV risk mitigation. The authors review key moral dilemmas facing clinicians and patients who must navigate the reversal of longstanding dogma against breastfeeding and provide recommendations for implementation of a new ethical paradigm.

Since the first reported cases of perinatally acquired human immunodeficiency virus (HIV) in 1982, a generation born with HIV has reached adulthood. The authors conducted a scoping review of PubMed and Google Scholar for articles published between January 2000 and June 2023 to assess the long-term, multisystem health outcomes of this population. Long-term health outcomes studied in this population pertain to the effects of perinatal HIV (PHIV) infection and life-long antiretroviral therapy on the endocrine, reproductive, psychosocial, neurobehavioral, immunologic, and cardiovascular systems. Holistic health of all body systems should be considered in the long-term care of people with PHIV.

Although new pediatric human immunodeficiency virus (HIV) infections have declined in the Asia-Pacific region, coverage of interventions to prevent vertical HIV transmission remains inconsistent. The TREAT Asia pediatric HIV cohort includes data from ∼7700 children and adolescents with HIV (90% perinatally acquired) who have been under care at 18 centers in six Asian countries. Research on their HIV treatment outcomes has been complemented by studies on coinfections and comorbidities. These studies have shown that greater attention is needed to support and sustain clinical and social outcomes as children with perinatal HIV age into adulthood and transition to adult HIV care.

Substantial progress in preventing vertical human immunodeficiency virus (HIV) transmission has led to a dramatic decline in new pediatric HIV infections. Alongside this success, a growing population of children who are HIV-exposed but uninfected face unique health challenges due to a variety of risk factors. Recommendations for healthcare providers caring for this population include optimizing and integrating general and HIV-related care for both mother and child through comprehensive care packages. Further research and multidisciplinary approaches are needed to address the long-term health implications for this vulnerable population.

Perinatally acquired human immunodeficiency virus (HIV) has the potential to affect neurodevelopment and long-term cognitive and behavioral outcomes. Early, consistent viral suppression through antiretroviral therapy is a priority for protection of neurodevelopment. Monitoring of neurodevelopment and cognitive functioning, referral for appropriate interventions, caregiver/family support, and assessment of mental health, socioeconomic, and environmental risks are important to optimize health and well-being. Support for medication and health care adherence may be necessary to sustain best outcomes.

The Penta Network has made significant strides in pediatric human immunodeficiency virus (HIV) research, initially focusing on clinical trials for children in Europe, before expanding globally to countries with high HIV prevalence. Key contributions include the ODYSSEY trial, which established dolutegravir as a superior treatment for children and the Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies consortium, aimed at developing strategies for HIV remission. The ongoing empirical and thrive projects address advanced HIV disease, particularly severe pneumonia and postdischarge mortality in children. Going beyond clinical trials, the Penta Network also plays a key role in bringing stakeholders and industry together to achieve better antiretroviral formulations for children.

In virtually all people living with HIV-1 (PLWH), including children, HIV-1 integrates and becomes latent in CD4 T cells, forming a latent HIV-1 reservoir that current antiretroviral drugs and immune surveillance mechanisms cannot target. This latent infection in CD4 T cells renders HIV-1 infection lifelong and incurable. Consequently, there is intense research focused on identifying therapeutic strategies to reduce and control the latent reservoir, aiming to avert a lifetime of antiretroviral therapy for PLWH. This review discusses the global efforts for children and adolescents living with HIV-1.

Despite increased uptake of antiretroviral therapy (ART) among pregnant people living with human immunodeficiency virus (HIV), vertical transmission remains the most important route of pediatric HIV acquisition. The numbers of HIV acquisitions in infancy have remained alarmingly stagnant in recent years. It is evident that additional strategies that can synergize with ART will be required to end the pediatric HIV epidemic. In this review, we discuss the potential for immune-based interventions that can be administered in conjunction with current ART-based strategies to the birthing parent for prevention of vertical transmission of HIV-1, and the potential challenges associated with each approach.

Managing human immunodeficiency virus (HIV) during pregnancy requires attention to psychosocial aspects of maternal health in addition to providing medical and obstetric care. Ideal care plans promote sustained HIV suppression and optimize maternal health prior to conception. Engagement with maternity services creates opportunities to support women with HIV to remain engaged in life-long care, monitor their health frequently, screen for co-morbid conditions, and develop a personalized antiretroviral therapy adherence strategy. This article summarizes antiretroviral drug use in pregnancy, pregnancy outcomes in women with HIV, and the key elements of providing holistic care.

While tuberculosis (TB) is an ancient disease, its global prevalence and concomitant human immunodeficiency virus (HIV)-1 infection have hampered efforts at effectively controlling TB in children in many countries where these 2 pandemics coexist. This review briefly discusses the current status of TB prevention strategies including preventative regimens designed to prevent the progression of latent TB infection to active disease, current recommendations regarding treatment of TB disease, and the problematic nature of diagnosing TB in children living with HIV. Promising recent data regarding novel diagnostic techniques that rely upon detecting Mycobacterium tuberculosis molecular components in blood will be reviewed.

The clinical trial networks that included a maternal-child focus have evolved since first funded by NIH in the 1990s. Since then, US domestic and international sites were combined into one network, with a focused agenda on therapeutics (for both prevention and treatment), human immunodeficiency virus (HIV) cure, tuberculosis, and complications of HIV, largely specific to the brain. Key to the success of the network has been a strong partnership with the community, collaborations with industry and other strategic partners, and recognition that one size does not fit all when it comes to antiretrovirals, diagnosing and treating TB, and other treatments for our populations.

Hypoxic ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy and results in significant morbidity and mortality. Long-term outcomes of the condition encompass impairments across all developmental domains. While therapeutic hypothermia (TH) has improved outcomes for term and late preterm infants with moderate to severe HIE, trials are ongoing to investigate the use of TH for infants with mild or preterm HIE. There is no evidence that adjuvant therapies in combination with TH improve long-term outcomes. Numerous trials of various adjuvant therapies are underway in the quest to further improve outcomes for infants with HIE.

Parents of newborns with hypoxic ischemic encephalopathy (HIE) can face communication challenges in the neonatal intensive care unit. Both specialty palliative care and primary palliative care trained clinicians can assist parents as they navigate traumatic experiences and uncertain prognoses. Using evidence-based frameworks, the authors provide samples of how to communicate with parents and promote parent well-being across the care trajectory. The authors demonstrate how to involve parents in a shared decision-making process and give special consideration to the complexities of hospital discharge and the transition home. Sustained investment to guide the development of effective communication skills is crucial to support families of infants with HIE.

Hypoxic ischemic encephalopathy (HIE) in neonates can cause severe, life-long functional impairments or death. Treatment of these neonates can involve ethically challenging questions about if, when, and how it may be appropriate to limit life-sustaining medical therapy. Further, parents whose infants suffer severe neurologic damage may seek recourse in the form of a medical malpractice lawsuit. This study uses several hypothetical cases to highlight important ethical and legal considerations in the care of infants with HIE.

Historically, neonatal neuroscience boasted a robust and successful preclinical pipeline for therapeutic interventions, in particular for the treatment of hypoxic-ischemic encephalopathy (HIE). However, since the successful translation of therapeutic hypothermia (TH), several high-profile failures of promising adjunctive therapies, in addition to the lack of benefit of TH in lower resource settings, have brought to light critical issues in that same pipeline. Using recent data from clinical trials of erythropoietin as an example, the authors highlight several key challenges facing preclinical neonatal neuroscience for HIE therapeutic development and propose key areas where model development and collaboration across the field in general can ensure ongoing success in treatment development for HIE worldwide.