The Road to Zero Perinatal HIV Transmission in the United States

In this issue of Pediatrics, Lampe et al¹  leveraged data from the National HIV Surveillance System to evaluate trends of annual perinatal HIV diagnoses per 100 000 live births and rates of perinatal HIV transmission events among infants born to women with diagnosed HIV in United States. This allowed the assessment of progress toward achievement of the CDC’s perinatal HIV transmission elimination targets almost a decade after they were established. The authors demonstrate remarkable declines in these rates from 2010, with achievement of both elimination benchmarks in 2019 of fewer than 1 case of perinatal HIV diagnosed per 100 000 live births and a transmission rate of less than 1%. These laudable accomplishments have been made possible through the decades-long coordinated multidisciplinary and multisectoral efforts of HIV research, public health agencies, and advocacy communities. These efforts serve as a model of evidenced-based science leading to effective health and policy changes. However, as Lampe et al¹  note, these gains have not been realized by all communities equitably. Disparities persist in racial and ethnic minority communities that have been disproportionately burdened by the HIV epidemic, with transmission rates in 2019 between 1% and 2% among Hispanic or Latino ethnicity and those in the “other races” category that includes American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, and multiracial persons.

Before the advent of antiretrovirals for prevention of mother-to child-transmission of HIV, one third of perinatal transmission events occurred before delivery or in utero, with the remaining during parturition and throughout postpartum breastfeeding.²  Once diagnosed, linkage to care, early antiretroviral therapy initiation, and adherence is critical to achieving rapid and durable viral suppression and immune reconstitution, which improve individual health and prevent onward transmission of HIV. In the United States though, the likelihood of reproductive age individuals living with undiagnosed HIV infection is higher among Black and Hispanic individuals.³  Syndemics, defined as 2 or more interacting, co-occurring or sequential diseases or health conditions and the social and environmental contributors that exacerbate or enhance the negative health effects of any or all diseases involved, likely play a role.⁴  These include but are not limited to structural determinants of health, such as housing and food insecurity, medical mistrust, stigma, intimate partner violence, mental health issues, and substance use.^5–7  These coalesce in a final common pathway leading to poor access to testing and care for HIV and sexually transmitted infections.⁸  In fact, identifying individuals and linking to critically needed HIV care has remained elusive despite numerous systematic efforts from the public health system, and the only reliable gateway to a diagnosis and life-saving care has been when these individuals become pregnant and seek prenatal care.

Much work remains to close the science-to-service gaps, as 16% to 30% of pregnant individuals diagnosed at or after delivery resulted in perinatal transmission of HIV.⁹  Important implementation science is needed to uncover individual, health system, and provider level challenges and implement interventions that will improve the delivery and uptake of culturally competent, unbiased, health care among diverse communities. Multisectoral, coordinated initiatives, like the US Department of Health and Human Services Ending the HIV Epidemic initiative¹⁰  strategically leveraged to access disproportionally affected communities with high HIV burden, identify more reproductive age individuals with undiagnosed HIV and link them to care.

Although interventions for the prevention of perinatal HIV transmission have matured since the seminal AIDS Clinical Trials Group 076 study,¹¹  which first evaluated HIV treatment in pregnant individuals, much work remains to advance new therapeutics in pregnancy. The safety and toxicity profile of therapeutics in pregnancy and in infants exposed to and with HIV has been a major focus of National Institutes of Health-funded HIV clinical trial networks. Scientific and ethical-legal-regulatory hurdles have often been cited as the rationale for requiring additional safeguards before studying interventions in pregnancy and often become barriers to obtaining critically needed data to support the use of these agents by pregnant individuals. Oral and topical forms of HIV pre-exposure prophylaxis only recently began safety and toxicity studies in pregnancy, representing an over 10-year delay since seminal studies demonstrated the safety and efficacy of these modalities in preventing HIV acquisition among nonpregnant adults. Such delays and other barriers to accomplishing needed research hamper our efforts in expanding safer alternative regimens for women and their infants and must be comprehensively addressed. Less mature in the research pipeline but equally important are multiple prevention technologies or approaches that offer women of reproductive age combined prevention options for pregnancy, sexually transmitted infections, and HIV. Among those who receive an HIV diagnosis and are ready to initiate antiretroviral therapy, there are long-acting injectables, like cabotegravir and rilpivirine, for which studies in pregnant people are needed and being planned.

A change in paradigm for inclusion of pregnant and lactating individuals in research is needed and is a focus of the US Task Force on Research Specific to Pregnant Women and Lactating Women.¹²  The World Health Organization, in collaboration with the International Maternal and Pediatric and Adolescent Clinical Trials, and the International AIDS Society recently published a proposed framework to accelerate the inclusion of women earlier in the drug development pipeline for HIV prevention and treatment.¹³  As Lampe et al¹  noted, intervention modalities demonstrating safety and efficacy under rigorously designed, ideal study conditions in trials for licensure, should be followed by monitoring for safety events in real-world settings after drug approval.

Lampe et al¹  argue that lessons learned from having successfully implemented this model can be extended to other infectious diseases. Indeed, the coronavirus disease 2019 pandemic has demonstrated the same disparities among racial and ethnic minority populations. Similar approaches that leveraged synergies between the same stakeholders were implemented to help ameliorate poor health outcomes across patient populations. Some approaches leveraged rapidly developed studies in individuals who are not pregnant, including novel designs and extant research infrastructures, to study new therapeutics and vaccines in individuals who were pregnant. Fortunately for individuals with coronavirus disease 2019 who are or may become pregnant, vertical transmission is a rare event and the untoward consequences to the infant are not commensurate or as durable as with HIV. That was not the case with Zika virus and may not be for other emerging infectious diseases either.¹⁴  The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision, the less reactive we will need to be when new transmissible infections appear at our doorstep. Doing so will enable us to reallocate precious public health response time and efforts from mitigation to prevention.