Postpartum Mother-To-Child Transmission of HIV in a Breastfeeding Infant

The infant was born at 39 weeks' gestation weighing 2945 g. An inherited genetic disorder was diagnosed at birth with referrals for genetic counseling and evaluation. The NYS NBS dried blood sample, collected within 48 hours after birth, was negative for maternal HIV-1 immunoglobulin G antibodies; the result is a proxy for maternal HIV status at delivery. Nonspecific symptoms, unrelated to the inherited genetic disorder, were first documented at the age of 15 weeks when the infant presented with a 10-day history of fever, dry cough, posttussive vomiting, diarrhea, and sneezing. Sneezing subsided but the remaining symptoms persisted and progressed to include decreased appetite, refusal to breastfeed, and vomiting with oral intake.

The infant was reevaluated at 17 weeks and sent from an ambulatory clinic to the emergency department (ED) for supportive therapy including rehydration. Weight gain was stable on the World Health Organization Growth Standard for weight and age.⁶  Mixed feedings of breast milk plus formula and then solids were noted at 15 weeks and 5.2 months, respectively. There was no indication that the infant received banked or shared breast milk or premasticated food.

The infant was next evaluated at 23 weeks, with a primary complaint of lingering cough. Between ages 23 and 27 weeks, the infant was evaluated by different subspeciality providers to address severe persistent cough and feeding and swallowing difficulties. A diagnosis of gastroesophageal reflux disorder was made, and treatment was initiated. At the 6-month well child visit, poor weight gain was noted (<10th percentile). At 27 weeks, the infant was seen in an ED for respiratory decompensation and was admitted to the hospital. The infant remained hospitalized for nearly 2 months with complications that required rescue respiratory interventions. A laboratory-confirmed HIV diagnosis (Table 1) occurred on day 6 of hospitalization at the age of 28 weeks (6.5 months). HIV-1 viral load at diagnosis was >10 000 000 copies per mL (7 log copies per mL); cluster of differentiation 4 T lymphocyte count was 278 cells per mm³. Bronchial lavage identified Pneumocystis jirovecii pneumonia. Between the age of 15 weeks and diagnosis with HIV, the child had 11 medical care encounters inclusive of EDs, medical subspecialists (pulmonologist, neurologist, and gastroenterologist), and routine pediatric care. Anti-infectives were not administered until after acute hospitalization.

At delivery, the mother was married and in her early thirties. The first prenatal visit occurred at 10 weeks' gestation, followed by regular prenatal care and an uncomplicated pregnancy. Maternal prenatal testing (Table 2) indicated positive group B Streptococcus, no documented sexually transmitted infections, a negative first trimester HIV test (4th generation antigen [Ag] and antibody [Ab]) and another negative HIV test at labor and delivery (3rd generation rapid HIV-1 and HIV-2 Ab); the latter may have missed acute infection. Hospital policy, driven largely by its location in a high HIV prevalence area, requires expedited testing at labor and delivery, if no maternal third trimester HIV test is documented in the medical record.

The mother attended 3- and 6-week postpartum visits. At 15 weeks postpartum, she presented to her primary care physician with a 7-day history of tactile fever, chills, myalgia, vomiting, headache, dizziness, and itchy eyes. The presumptive diagnosis was a viral upper respiratory infection. One week later, she presented to the ED and reported severe whole-body ache, fever, debilitating headache, and nausea. Laboratory studies, including a hepatitis panel, were performed; HIV screening was not included. The maternal HIV diagnosis was made 4 days after the infant’s diagnosis. The mother reported monogamous sex and no history of injection drug use. Partner screening was not performed during the antenatal or postpartum period. Travel to a high prevalence area, outside of the United States by the partner, was noted in the medical record. However, the timing of travel was not specified.

The Centers for Disease Control and Prevention’s approach to the elimination of MTCT focuses on public policy, public health infrastructure, and equitable health care access and quality, with universal opt-out HIV screening.⁷  In practice, the prevention of MTCT has been focused primarily on maternal interventions in the prenatal and immediate postpartum periods and less on interventions such as couples counseling and testing,^8,9  preexposure prophylaxis in serodiscordant couples,¹⁰  and preventive care during preconception and interpregnancy periods.^11,12  The transmission event we describe was confirmed at the age of 6.5 months and likely occurred via breastfeeding in the context of mixed feeding in an infant whose mother seroconverted postnatally. The infant was diagnosed with HIV, roughly 3 months after first presenting to health care with nonspecific, deteriorating symptoms and after 11 health care encounters during which the mother was evaluated twice with worsening symptoms.

The majority of the medical care encounters for mother and child occurred within a single facility with colocated maternal and infant health services and pediatric subspecialty care. Prompt consideration of acute HIV infection (AHI) may have been hindered by the 3 documented negative maternal HIV tests (first trimester, at labor and delivery, and NBS). Transmission to the infant before or during birth cannot be definitively excluded on the basis of the negative maternal rapid test at labor and delivery or the negative NBS test. All US Food and Drug Administration–approved HIV rapid tests report sensitivities of >99.5% and specificities in the range of 99.7% to 99.9%.¹³  The NBS test identifies maternal HIV-1 immunoglobulin G antibodies passed from mother to infant but may have produced a false-negative result if the mother was in the acute phase of HIV infection. The sensitivity of the NBS test is 99.4% and specificity is 99.8%; these values are based on true-positive status and do not account for the time, postinfection, required for the test to become reactive.¹⁴  The infant’s diagnostic bloodwork at 6.5 months indicated likely AHI (ie, high levels of HIV-1 RNA, in combination with a positive rapid HIV Ag and Ab test and a negative HIV-1 and HIV-2 Ab differentiating test). Nonetheless, both mother and infant presented on multiple occasions with on-going complaints and significant health deterioration for the infant at a facility with a long history of diagnosing and treating children and adults with HIV. No consideration of AHI was evident in the medical record for either mother or child, and no postnatal HIV-related testing was conducted before the infant’s hospitalization.

The timing of maternal HIV infection and seroconversion is critical for preventing transmission to breastfeeding infants. Before ART, studies demonstrated lower rates of HIV transmission during the first 6 months of life with exclusive breastfeeding (EBF), as compared with that of mixed feeding.¹⁵  In the context of effective ART, data are inconclusive on whether EBF or mixed feeding impact transmission of perinatal HIV.¹⁶  Transmission appears most frequent among infants who are younger than the age of 9 months at the time of maternal seroconversion, with the highest risk in the first 3 months of life.¹⁷  In one study, infants born to mothers newly diagnosed with HIV ≥3 months postpartum had higher plasma viral loads, and their viral loads declined more slowly over the first 9 to 12 months than did infants born to chronically infected women, who had a low, but constant risk of breastfeeding-associated transmission.¹⁷  Although the American Academy of Pediatrics recommends EBF for infants aged <6 months and continued breastfeeding for one year or longer,¹⁸  the recommendation in the United States for women living with HIV is to abstain from breastfeeding. Therefore, a heightened level of awareness of the risk during breastfeeding is warranted and should include HIV risk assessment of mothers during the breastfeeding period, an emphasis on the benefits of EBF^19,20  and avoidance of breast milk from informal sharing networks.²¹ 

Current recommendations for HIV testing during pregnancy do not extend to the postnatal period. Moreover, the recommendation to screen for HIV in sexual partners of pregnant people is not routinely practiced and uptake of partner screening is poor.^8,22  Biosocial intersectionality, such as couples’ assumptions and partner dynamics, including power imbalances, is critical to screening and risk assessement^23,24  (eg, many couples assume HIV negative testing in the pregnant individual infers partner seronegative status, making partner testing unnecessary during the antenatal and postpartum periods).²⁵  NYS public health law requires an offer of HIV testing at least once to individuals aged ≥13 years who receive hospital or primary care services.²⁶  The Centers for Disease Control and Prevention and US Preventive Services Task Force also recommend that HIV screening be included in routine clinical care in all health care settings and more frequently for persons at increased risk.^27,28  These recommendations are insufficient to protect infants whose mothers seroconvert in the postpartum period. The assessment of risks to mother and infant, including maternal risk behaviors and partner testing, must extend beyond pregnancy and be a routine component of prenatal, discharge, postpartum, and early pediatric care, with messaging tailored to mothers and their partners about prevention of HIV and sexually transmitted infections.^11,29  Even with extensive screening, AHI may be missed but HIV should always be considered when individuals are symptomatic, partners have not been (recently) screened (as part of routine and “sick visit” care), and even when maternal testing was recent and negative.

We acknowledge the contributions of Bridget J. Anderson, PhD, and Sarah Braunstein, PhD, for their investigation and critical review of this work.

Ab

antibody

AHI

acute HIV infection

Ag

antigen

ART

antiretroviral therapy

CDC

Centers for Disease Control and Prevention

EBF

exclusive breastfeeding

ED

emergency department

MTCT

mother-to-child transmission

NBS

newborn screening

NYS

New York State