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Epidemiology of Perinatal HIV Transmission in the United States in the Era of Its Elimination

Nesheim, Steven R. MD*,†; FitzHarris, Lauren F. MPH*,†,‡; Mahle Gray, Kristen MPH*,§; Lampe, Margaret A. RN, MPH*,†

Author Information

From the *Division of HIV/AIDS Prevention

†Epidemiology Branch

‡ICF

§HIV Incidence and Case-Surveillance Branch, Centers for Disease Control and Prevention, National Center for HIV, Viral Hepatitis, Sexually Transmitted disease, and Tuberculosis Prevention, Atlanta, Georgia.

Accepted for publication January 11, 2019.

The authors have no funding or conflicts of interest to disclose.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Address for correspondence: Steven R. Nesheim, MD, Centers for Disease Control and Prevention, 1600 Clifton Road MS E-45, Atlanta, GA 30329. E-mail: [email protected].

The Pediatric Infectious Disease Journal: June 2019 - Volume 38 - Issue 6 - p 611-616
doi: 10.1097/INF.0000000000002290
  • Free

Abstract

The estimated annual number of infants born with perinatally acquired HIV infection in the United States has decreased nearly every year since the early 1990s, 97% overall from its peak in 1991 (n = 1760)1 to 2015 (n = 53),2 the last year for which there are published data. Estimated incidences for those years are 42.8 and 1.3 per 100,000 live-born infants, respectively.2,3 Despite the success in reducing perinatal HIV transmissions, racial disparities remain, and missed opportunities for key interventions continue for some women with HIV, particularly during the postpartum period.

Goals for elimination of perinatal HIV transmission have been established for the United States: (1) incidence less than 1 per 100,000 live births and (2) mother-to-child transmission rate less than 1%.4 The United States may be achieving its incidence goal; the mother-to-child transmission rate cannot be determined without a valid estimate of the number of women with HIV infection delivering annually. Enhanced Perinatal Surveillance (EPS) of the Centers for Disease Control and Prevention (CDC)5 reported perinatal HIV transmission rates in 2006 (1.7%) and 2008 (1.6%), comparable to those of other high-income countries during that period (United Kingdom, 2000–2006, 2%6; Spain, 2000–2007, 1.6%7; Canada, 1990–2010, 2.9%8). The latest available US rate is much higher than the more recent rates in the United Kingdom of 0.45% during 2010–20119 and 0.3% during 2012–2014.10 If the number of women with HIV delivering infants annually remains as high as was estimated for 2006—8700 per year—more current perinatal transmission rates would clearly be less than 1% (53/8700 = 0.006, 0.6%). Even if the number of deliveries has decreased to 5000 or less11—as seems more likely (see Annual Number of Births To Women with HIV)—the perinatal transmission rate is approximately 1% nationwide (53/5000 = 0.0106, 1.1%).

As of 2010, it was estimated that in the United States more cases of perinatal HIV had been prevented than had occurred (21,956 vs. 21,003) in the period since antiretroviral prophylaxis was recommended for all pregnant women with HIV infection. During the same period (1994–2010), approximately 100,207 infants were prenatally exposed to antiretrovirals (ARVs).12

From early in the epidemic, blacks/African Americans (hereafter referred to as blacks) and Hispanics/Latinos have been disproportionately represented among infants born with HIV infection. In 2010, though 13% of the total US population (and 15% of infants less than 1 year old) were black, 45% of males and 67% of females with diagnosed HIV infection, greater than 13 years old, were black.13 The incidence of perinatally acquired HIV among black infants has in recent years declined in parallel to the incidence among all US-born infants, but remains over 5 times as high.2

Along with racial disparities among perinatally infected and exposed infants, missed opportunities for key interventions continue to occur. To appropriately direct resources, policy actions and research, it is important to review the epidemiology to date, and to continue monitoring outcomes and other health indicators for childbearing age women living with HIV and their infants.

PERINATAL HIV PREVENTION CASCADE

The Perinatal HIV Prevention Cascade conceptualizes interventions to prevent perinatal transmission and their converse, so-called missed opportunities.4 Interventions include receipt of prenatal care, receipt of ARV during pregnancy and intrapartum period, receipt of neonatal ARV, maternal viral suppression, elective Cesarean delivery and forgoing breast-feeding. Missed opportunities can be expressed as a percentage among all mother–infant pairs in which the mother has HIV infection (ie, perinatal HIV exposure), or among those mother–infant pairs in whom transmission occurred (ie, mothers of infants with HIV infection). The most broad-based and long-lasting source of data on missed opportunities is EPS, which provides the majority of data below. For the period since cessation of EPS in 2010, we use statewide surveillance data, or data on perinatal HIV exposure, which is provided to CDC by some states.

Among HIV-exposed infants (Table 1A), the proportion with no or inadequate prenatal care was between 21% and 31% in recent years14,15; note that EPS asked only if prenatal care had occurred and did not characterize the adequacy of the prenatal care. Prenatal ARV use was in the low 80% range in the early 2000s5,16,17 and has increased recently to 86%–93% according to nearly every surveillance-based report.14,15,18–20 There have been similar increases in ARV administered in labor and delivery.14 Neonatal ARV use was already in 93%–97% range in the early 2000s5,16,17 and remains high recently.14,19 Elective cesarean delivery has remained near 40%.5,14,16 Breast-feeding has occurred in about 1% of US-born infants with perinatal HIV exposure.14,17

T1A
TABLE 1A.:
Perinatal Cascade Among HIV-exposed Uninfected Infants and Their Mothers, United States 2000–2015

Among infants with HIV infection (Table 1B), the numbers are somewhat different, with recent data showing inadequate prenatal care in 44%–58%14,22 and no prenatal care in 11.2% in National HIV Surveillance System23; prenatal ARV slightly less than 50%5,14,23; and ARV in labor and delivery only 50%–62%.5,14,23 Neonatal ARV use among infants is around two-thirds in most reports,17,23 though 100% of infants received neonatal ARV in one report.14 Elective cesarean delivery is only slightly less than among HIV-exposed infants,14,23 but as many as 10% of infants with HIV infection in the United States have breast-fed in recent years.5,14,23

T1B
TABLE 1B.:
Perinatal Cascade Among HIV-infected Infants and Their Mothers, United States 2005–2014

Prenatal HIV testing is part of the perinatal prevention cascade, and CDC’s recommendation for universal opt-out prenatal HIV testing was published in 2006.24 Nevertheless, the overall prenatal HIV testing rate has not exceeded 76% since 2006 in national data,25–28 although there are higher percentages in some states. The timing of mother’s HIV diagnosis—not typically part of the Cascade—relates to when the mother’s HIV diagnosis was determined, for example, before or during pregnancy. Among HIV-exposed infants (Table 2A), approximately two-thirds of mothers had HIV diagnosed before pregnancy during 2000–2008,5,16 but that percentage has increased to 75%–82% in nearly every state surveillance-based report from 2005 to 2015.14,15,19,21,29 Concurrently, among mothers of HIV-exposed but uninfected infants, the percent with HIV diagnosed during pregnancy has declined from 26%–30% during 2000–20085,16 to 16%–20% in reports with data through 2014,14,19 even below 10% in one analysis,15 and diagnosis at/after delivery has declined to less than 10%.14,19 In contrast, among infants with HIV infection (Table 2B), maternal HIV is diagnosed before pregnancy in only slightly more than 50%,14,22,23 underscoring the importance of timely diagnosis. In mothers of infants with HIV infection, diagnosis is made during pregnancy in 14%–17%. As many as 30% of mothers of HIV-infected infants are not diagnosed until or after delivery. It is less clear whether there is a trend in the percent of mothers who received their HIV diagnoses at or after delivery; in the National HIV Surveillance System, the percent diagnosed at or after delivery declined from 30% (during 2002–2005) to 21% (during 2010–2013),23 but EPS reported 29% “late” diagnosis (during 2005–2008).5 Florida recently reported that 24% of diagnoses are at/after delivery among mothers of infants with HIV.14

T2A
TABLE 2A.:
Timing of Maternal HIV Diagnosis of HIV-exposed Uninfected Infants, United States 2000–2015
T2B
TABLE 2B.:
Timing of Diagnosis of Mothers of Infants With HIV Infection, United States 2002–2014

Repeat prenatal HIV testing, usually in the third trimester, has not usually been incorporated into the Cascade, and there is little data on the uptake of this recommendation.30 When large populations are examined, it appears that 7%–18% of infants with perinatal HIV infection in the United States are born to women who had acute HIV infection during pregnancy.14,31,32 It remains to be seen whether this proportion is dramatically increasing.14

ARVs to prevent infant acquisition can be effective even if begun only at birth,33 and it has been shown that combinations of 2 or 3 ARVs are more effective than a single ARV in this context.34 Such combinations are considered for infants whose mothers received no prenatal antiretroviral therapy (ART), had not achieved viral suppression at delivery or were identified during or immediately after labor. In some of these situations, administration of 3 ARVs as prophylaxis is essentially the same as treating presumptively.35 In the United States, 10% of infants in Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study received a prophylactic regimen of more than one drug during 1995–2009.36 Data from the US Women and Infants Study (WITS), Pediatric AIDS Clinical Trials Group 219C study and the PHACS/SMARTT study showed an increase in the practice from 2% to 15% during 1996 and 2015.37

The cascade does not include interventions related to contraception and family planning services for people with HIV of reproductive age. In one analysis of women in HIV care, nearly 80% reported at least one unplanned pregnancy.38

ANNUAL NUMBER OF BIRTHS TO WOMEN WITH HIV

The number of women with HIV delivering infants in the United States has not been accurately known since completion of CDC’s Survey of Childbearing Women in 1995, which estimated it as approximately 6000.39,40 CDC estimated the number in the year 2000, at which time it was thought to be unchanged since 1995; it was estimated again in 2006, at approximately 8700 births per year, an approximately 30% increase.41 Given what we know about the uptake of preventive interventions—for example, rates of antiretroviral use during pregnancy; efficacy of ART regimens in suppressing maternal viral load—the number of women with HIV delivering infants in the United States is almost certainly lower, given the number of infants born with infection in recent years, for example, 53 in 2015.2 Furthermore, the number of perinatal exposures has declined 15%–20% in nearly every state which routinely reports these numbers. Finally, the present birth rate in women with HIV infection (approximately 7%42), and the number of childbearing age women with HIV,43 would yield a number lower than 8700 (about 95,000 × 0.07 = 6600). If the birth rate has not generally increased to 7%, an even lower number of deliveries would be expected. Overall, the number of women with HIV delivering infants may be fewer than 5000.11

WOMEN LIVING WITH HIV INFECTION

Clearly, for a discussion of perinatal HIV transmission, an understanding of the population of women with HIV infection is vital. A decline in the number of deliveries to women with HIV infection is consistent with changes in the population of women of childbearing age (13–44 years, for purposes of this article) with HIV infection. Nationwide, during 2008–2014, HIV diagnoses among women of childbearing age declined approximately 30%.43 Even among the states with 10 or more infants born with HIV during 2010–2013 (CA, FL, GA, IL, LA, MD, NJ, NY, PA, TN and TX),23 the number of HIV diagnoses among women declined 15%–52.8%.43 Among persons acquiring HIV through heterosexual contact, the estimated annual percentage decrease in recent years was 6.3%.44 During 2008–2014, the number of women of childbearing age living with HIV declined approximately 10%.43 In the states with the highest numbers of infants born with HIV during 2010–2013 (listed above), the numbers of women of childbearing age living with HIV declined, with the exceptions of Texas and Georgia, with increases of 10.4% and 9.1%, respectively.43

For all transmission risk categories, transmission can occur during 2 periods: (1) before a diagnosis is made in a person with HIV infection, and (2) after diagnosis, when the person’s HIV viral load is above the limit of detection. Transmission risk potential—defined as the proportion of the year in which an individual’s HIV viral load is above 1500—was highest among black Americans (52.1%); viral suppression was lowest among blacks 13–24 years old45 in 2014. The mean number of days in the year with viral load above 1500 copies/mL was 178 for males of any race whose transmission category was heterosexual contact (second only to men who have sex with men and inject drugs), and 182 for females of any race whose transmission category was heterosexual contact (second to females who inject drugs and female with “other” risk).45 Though new cases in women are clearly those with a direct effect on infants acquiring HIV, it is also clear that preventing new cases in women is directly related to diagnosing and appropriately treating men of reproductive age. It can be speculated that the best way to prevent cases of infant HIV acquisition is to treat adult women—and men—of reproductive age effectively. Effective treatment is often described in terms of a Continuum of Care, which includes Diagnosis, Linkage to Care, Retention in Care, Prescription of ART and Suppression of HIV.

We have seen in the “Perinatal Cascade” data that a large majority of pregnant women with HIV are on ART. Since many adult women with HIV seem to be identified during pregnancy (or among those with diagnosis made before pregnancy, appear to recommit to treatment during pregnancy), it would seem to follow that pregnancy is a good entry point for starting—and remaining on—effective ART. In reality, only 37%–39% of postpartum women are retained in care.46,47 ART use is self-described by no more than 70% of postpartum women,48–5034% if pill counts are used49 and viral suppression is achieved by 30%–61% of postpartum women.47,51

In contrast to pregnant or postpartum women, the Continuum of Care is somewhat better for women, overall. Diagnosis of HIV is known by more than 80%–88% of women with HIV infection.52,53 Linkage to care is achieved in 68%–81%.52,54,55 Retention in care is achieved by 40%–50% of women in most reports,52–56 with 75%–80% in 2 larger reports, one of which is surveillance based.57,58 ART is used by 34%–50% of women overall and by 86% of those who are in medical care.59 Viral suppression is achieved in a wide range of women, 32%–71%.53,54,60

The time between HIV infection and diagnosis for all adults of reproductive age is relevant to prevent perinatal transmission for the reasons stated above, that is, primary prevention of infection of women, and achieve viral suppression among women. From NHSS data, among all HIV transmission categories, the median time between infection and diagnosis was longest for heterosexual males, declining from 9.0 years in 2003 to 5.9 years in 2011. For heterosexual women, also for 2003 and 2011, the median times were 5.9 and 3.7 years, respectively. In 2003, these 2 times were longer than those for any other transmission category.61 By 2015, the median time between infection and diagnosis was 2.5 years for women infected by heterosexual contact, but men infected by heterosexual contact continued to have the longest median time, 4.9 years.62

WHERE ARE THE WOMEN WITH HIV IN THE UNITED STATES?

The geographical distribution of HIV among women is high along the Atlantic and Gulf coasts, with foci in major urban areas (New York, Philadelphia, District of Columbia-Baltimore, Miami, Atlanta and Houston)43 (see Fig. 1). In addition, prevalence is high along much of the Atlantic coastal plain beginning in Virginia, and in large areas of the Mississippi Delta, where some counties are comparable to the most affected neighborhoods of Washington, DC. Though the numbers of infants born with HIV in these rural areas are not as high as those in the urban areas, these pockets of rural poverty can be considered potentially vulnerable in years to come. Many of these areas coincide with the states with the highest ratios of women with HIV to men with HIV.63

F1
FIGURE 1.:
HIV prevalence among women, 13 years or older, by county, United States 2015.

SUMMARY

The epidemiologic context of infant HIV acquisition has changed substantially, including a decline in the incidence of HIV among women,44 in the annual numbers of HIV diagnoses among women of childbearing age and in the number of women of childbearing age living with HIV.43 The birth rate has increased among women with HIV,42 and the percentage of pregnant women with HIV diagnosed before pregnancy is increasing.14,19,21 Overall, the percentage of women living with HIV who have not been diagnosed is decreasing.64 Continued transmission to infants in the face of these changes is likely to be the result of incomplete uptake of prevention interventions and ongoing HIV transmission among women and men of reproductive age. Several trends among adults are notable: (1) delayed time to diagnosis for heterosexual young men, (2) longer period of transmissibility resulting from delayed time to diagnosis and (3) incomplete retention in care and adherence to treatment among women, particularly in the postpartum period. Recognizing that ongoing adult HIV transmission contributes to the numbers of new infant infections supports the alignment of concerns about perinatal HIV transmission with those related to HIV prevention and care for adults.

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Keywords:

epidemiology; HIV; infants; perinatal; pregnancy; United States

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