Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission. As active members of this task force, we urge all healthcare providers who care for pregnant individuals to prioritize reporting all ARV exposures to the registry.

INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

INTRODUCTION: The sexual and reproductive health of cisgender women with HIV is essential for overall health and well-being. Nationally representative estimates of sexual and reproductive health outcomes among women with HIV were assessed in this study. METHODS: Data from the Centers for Disease Control and Prevention's Medical Monitoring Project-including data on sexual and reproductive health-were collected during June 2018-May 2021 through interviews and medical record abstraction among women with HIV and analyzed in 2023. Among women with HIV aged 18-44 years (n=855), weighted percentages were reported, and absolute differences were assessed between groups, highlighting differences ≥|5%| with CIs that did not cross the null. RESULTS: Overall, 86.4% of women with HIV reported receiving a cervical Pap smear in the past 3 years; 38.5% of sexually active women with HIV had documented gonorrhea, chlamydia, and syphilis testing in the past year; 88.9% of women with HIV who had vaginal sex used ≥1 form of contraception in the past year; and 53.4% had ≥1 pregnancy since their HIV diagnosis-of whom 81.5% had ≥1 unintended pregnancy, 24.6% had ≥1 miscarriage or stillbirth, and 9.8% had ≥1 induced abortion. Some sexual and reproductive health outcomes were worse among women with certain social determinants of health, including women with HIV living in households <100% of the federal poverty level compared with women with HIV in households ≥139% of the federal poverty level. CONCLUSIONS: Many women with HIV did not receive important sexual and reproductive health services, and many experienced unintended pregnancies, miscarriages/stillbirths, or induced abortions. Disparities in some sexual and reproductive health outcomes were observed by certain social determinants of health. Improving sexual and reproductive health outcomes and reducing disparities among women with HIV could be addressed through a multipronged approach that includes expansion of safety net programs that provide sexual and reproductive health service coverage.

OBJECTIVE: The primary aim of this serial cross-sectional analysis is to estimate the total number of prevented perinatal HIV transmissions from the time of the initial recommendation for perinatal zidovudine (ZDV) prophylaxis in 1994 through 2020 in the US. METHODS: The estimated number of prevented transmissions was calculated as annual differences between expected and observed numbers of perinatal HIV transmissions. Annual expected number of transmissions was estimated by multiplying the annual number of births to women with HIV by 0.2255 (22.55%), i.e., the transmission rate of the control group in the ACTG Protocol 076 trial. We used published point estimates or, if only ranges were given, the midpoints of those ranges as the best estimates of the annual numbers of births to women with HIV and infants with perinatal HIV. When data were not available, we linearly interpolated or extrapolated the available data to obtain estimated numbers for each year. RESULTS: Between 1978 and 2020, the approximate number of live births to women with HIV was 191 267 (95% confidence interval [CI] 190 392-192 110) and for infants with diagnosed perinatal HIV, it was 21 379 (95% CI 21 088-21 695). Since 1994, the annual number of infants born with HIV decreased from 1263 (95% CI 1194-1333) to 33 in 2019 (95% CI 22-45) and 36 in 2020 (95% CI 25-48), corresponding to a 97% reduction. Cumulatively, an estimated total of 22 732 (95% CI 21 340-24 462) perinatal HIV infections were prevented from 1994 through to 2020. CONCLUSION: The elimination of perinatal HIV transmission-accompanied by the cumulative number of prevented cases exceeding that of perinatal HIV infections-is a major public health achievement in the US.

BACKGROUND: A study from Botswana identified an increased risk of neural tube defects (NTDs) in infants of mothers with HIV who were treated with dolutegravir around the time of conception. We aimed to examine associations of dolutegravir use with NTDs and pregnancy loss using large health-care claims databases from the USA, a country with folic acid fortification of food. METHODS: In this cohort study, we analysed health-care claims data, recorded in the Merative MarketScan commercial database (MarketScan data) and Centers for Medicare & Medicaid Services Medicaid database (Medicaid data) from Jan 1, 2008, to Dec 31, 2020. We identified pregnancies with enrolment during their entire duration among women aged 15-49 years and we estimated time of conception. For each pregnancy, we determined HIV status and periconceptional exposure to dolutegravir or other antiretroviral agents. We estimated and compared the incidence rate of NTDs, stillbirths, and pregnancy loss (ie, spontaneous or induced abortions) by type of periconceptional antiretroviral exposure. We calculated adjusted risk ratios of the adverse outcomes using Poisson models adjusting for demographic and clinical factors. FINDINGS: Of 4 489 315 pregnancies in MarketScan data and 14 405 861 pregnancies in Medicaid data that had full enrolment, we identified 69 pregnancies in MarketScan data and 993 pregnancies in Medicaid data that were associated with HIV and periconceptional dolutegravir exposure. For women without HIV, the NTD rate was 4·1 per 10 000 live births (95% CI 3·9-4·3) in MarketScan and 5·7 per 10 000 live births (5·6-5·8) in Medicaid. No NTD cases were found among those with dolutegravir or non- dolutegravir antiretroviral drug exposure in the MarketScan data; only one NTD case was identified among women with dolutegravir, and three among women with non-dolutegravir antiretroviral exposure in Medicaid. After adjusting for covariates, there were no significant differences in risk ratios of NTD between groups with periconceptional dolutegravir or non-dolutegravir antiretroviral exposure and the group without HIV. However, compared with women without HIV, the risk of pregnancy loss was higher among women exposed to antiretroviral therapy: for dolutegravir exposure the adjusted risk ratio was 1·73 (95% CI 1·20-2·49) in MarketScan data and 1·41 (1·30-1·54) in Medicaid data; for non-dolutegravir antiretroviral exposure the adjusted risk ratio was 1·23 (1·10-1·37) in MarketScan data and 1·11 (1·07-1·15) in Medicaid data. INTERPRETATION: We studied the largest US cohort of women with periconceptional or early-pregnancy dolutegravir exposure. Our results do not show an increased risk of NTDs in exposed infants in the USA. Administrative databases can be used, with rigorous methodology, to study correlates of rare outcomes, such as NTDs, and to monitor for adverse pregnancy outcomes in women who receive antiretrovirals. FUNDING: US Centers for Disease Control and Prevention.

In 2012, the Centers for Disease Control and Prevention published a Framework for Elimination of Perinatal Transmission of HIV in the United States in Pediatrics, setting the goals of an incidence of <1 case of perinatal HIV per 100 000 live births, and a perinatal transmission rate of <1%. We used National HIV Surveillance System data to monitor the numbers of perinatally acquired HIV cases among US-born persons and perinatal HIV diagnosis rates per 100 000 live births to approximate incidence. Perinatal HIV transmission rates from 2010 to 2019 were calculated by using estimates of live births to women with an HIV diagnosis from the National Inpatient Sample, Healthcare Cost and Utilization Project. The annual estimated number of live births to women with diagnosed HIV decreased from 4587 in 2010 to 3525 in 2019, and the number of US-born infants with perinatally acquired HIV decreased from 74 in 2010 to 32 in 2019. Annual perinatal HIV diagnosis rates declined from 1.9 to 0.9 per 100 000 live births, and perinatal HIV transmission rates declined from 1.6% to 0.9%. Racial and ethnic disparities in HIV diagnosis rates persisted but declined substantially over the 10-year period. Both diagnosis and transmission rate elimination goals were first achieved in 2019. To maintain the elimination of perinatal HIV, and to eliminate racial disparities, the continued coordinated effort of health care and public health is required. The approach to perinatal HIV elimination is a public health model that can be replicated or expanded to areas beyond HIV.

Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes.

BACKGROUND: Among children with HIV infection, opportunistic illness (OI) rates decreased after introduction of highly active antiretroviral therapy (ART) in 1997. We evaluated whether such decreases have continued. METHODS: Data from the Centers for Disease Control and Prevention's National HIV Surveillance System for children with HIV living in the US during 1997-2016 was used to enumerate infants experiencing the first OI by birth year and OIs among all children <13 years of age (stratified by natality). We calculated the time to first OI among infants using Kaplan-Meier methods. RESULTS: Among infants born during 1997-2016, 711 first OIs were diagnosed. The percentage of the first OIs diagnosed in successive 5-year birth periods was: 60.0% (1997-2001), 24.6% (2002-2006), 11.3% (2007-2011), and 3.4% (2012-2016). For every OI, the number of first cases decreased nearly annually. Time to first OI increased in successive birth periods. Among children <13 years of age, 2083 OI were diagnosed, including Pneumocystis jiroveci pneumonia, candidiasis, recurrent bacterial infection, wasting syndrome, cytomegalovirus, lymphocytic interstitial pneumonitis, tuberculosis, nontuberculous mycobacteriosis and herpes simplex virus. The rate (#/1000 person-years) decreased overall (60-7.2) and for all individual OIs. Earlier during 1997-2016, rates for all OIs were higher among foreign-born than US-born children but later became similar for all OIs except tuberculosis. CONCLUSIONS: Among children with HIV in the US, numbers and rates of all OIs decreased during 1997-2016. Earlier, OI rates were highest among non-US-born children but were later comparable to those among US-born children for all OIs except tuberculosis.

OBJECTIVES: The risk of mother-to-child HIV transmission can be reduced to </=0.5% if the mother's HIV status is known before delivery. This study describes 2006-2014 trends in diagnosed HIV infection documented on delivery discharge records and associated sociodemographic characteristics among women who gave birth in US hospitals. METHODS: We analyzed data from the 2006-2014 National Inpatient Sample and identified delivery discharges and women with diagnosed HIV infection by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used a generalized linear model with log link and binomial distribution to assess trends and the association of sociodemographic characteristics with an HIV diagnosis on delivery discharge records. RESULTS: During 2006-2014, an HIV diagnosis was documented on approximately 3900-4400 delivery discharge records annually. The probability of having an HIV diagnosis on delivery discharge records decreased 3% per year (adjusted relative risk [aRR] = 0.97; 95% CI, 0.94-0.99), with significant declines identified among white women aged 25-34 (aRR = 0.93; 95% CI, 0.88-0.97) or those using Medicaid (aRR = 0.93; 95% CI, 0.90-0.97); among black women aged 25-34 (aRR = 0.95; 95% CI, 0.92-0.99); and among privately insured women who were black (aRR = 0.96; 95% CI, 0.92-0.99), Hispanic (aRR = 0.92; 95% CI, 0.86-0.98), or aged 25-34 (aRR = 0.96; 95% CI, 0.92-0.99). The probability of having an HIV diagnosis on delivery discharge records was greater for women who were black (aRR = 8.45; 95% CI, 7.56-9.44) or Hispanic (aRR = 1.56; 95% CI, 1.33-1.83) than white; for women aged 25-34 (aRR = 2.33; 95% CI, 2.12-2.55) or aged >/=35 (aRR = 3.04; 95% CI, 2.79-3.31) than for women aged 13-24; and for Medicaid recipients (aRR = 2.70; 95% CI, 2.45-2.98) or the uninsured (aRR = 1.87; 95% CI, 1.60-2.19) than for privately insured patients. CONCLUSION: During 2006-2014, the probability of having an HIV diagnosis declined among select sociodemographic groups of women delivering neonates. High-impact prevention efforts tailored to women remaining at higher risk for HIV infection can reduce the risk of mother-to-child HIV transmission.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services(dagger) (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.( section sign) Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

BACKGROUND: The benefits of combination antiretroviral (ARV) prophylaxis for infants whose HIV exposure is recognized near birth have been established, and the benefits of early ARV therapy are well known. Decisions about ARVs can be supported by the probability that the child has acquired HIV. METHODS: Using 2005-2010 data from Enhanced Perinatal Surveillance of the Centers for Disease Control and Prevention, we developed a tool for use at birth to help predict HIV acquisition of HIV-exposed infants to support ARV management. A logistic regression model, fit using a fully Bayesian approach, was used to determine maternal variables predictive of infant HIV acquisition. We created a score index from these variables, established the sensitivity and specificity of each possible score, and determined the distribution of scores among infants, with and without HIV, in our study population. RESULTS: Multivariable analysis of data from 8740 HIV-exposed infants (176 infected and 8564 uninfected) yielded 4 maternal variables in the perinatal HIV acquisition prediction model: sexually transmitted infection, substance use, last HIV viral load before delivery and ARV use. Using the regression coefficient estimates, we rescaled each possible score to make the maximum score equal to 100. For each score, sensitivity and specificity were determined; the area under the receiver operating characteristic curve was 0.79. Median index scores for infants with HIV and without HIV were 43 (first quartile 27 and third quartile 60), and 12 (first quartile, 0 and thirs quartile, 29), respectively. CONCLUSIONS: Decisions to begin infants on 3 ARVs-whether considered therapeutic or prophylactic-can be supported by data available on the day of birth.

The number of infants with HIV born in the United States has decreased for years, approaching the Centers for Disease Control and Prevention's incidence goal for eliminating perinatal HIV transmission. We reviewed recent literature on perinatal HIV in the United States. Among perinatally HIV-exposed infants (whose mothers have HIV, without regard to infants' HIV diagnosis), prenatal and natal antiretroviral use has increased, maternal HIV infection is more frequently diagnosed prior to pregnancy, and breastfeeding is uncommon. In contrast, mothers of infants with HIV are tested at a lower rate for HIV, receive prenatal care less often, receive antiretrovirals (prenatal and natal) less often, and breastfeed more often. The incidence of perinatal HIV remains 5 times as high among black than white infants. The annual number of births to women with HIV was estimated last for 2006 (8,700), but has likely decreased. The numbers of women of childbearing age living with HIV and HIV diagnoses have decreased. The estimated time from HIV infection to diagnosis remains long among women and men who acquired HIV heterosexually. It is important to review the epidemiology and to continue monitoring outcomes and other health indicators for reproductive age adults living with HIV and their infants.

OBJECTIVES: The annual number of women with HIV infection who delivered infants in the United States was estimated to be 8700 in 2006. An accurate, current estimate is important for guiding perinatal HIV prevention efforts. Our objective was to analyze whether the 2006 estimate was consistent with the number of infants with HIV infection observed in the United States and with other data on perinatal HIV transmission. METHODS: We compared the number of infants born with HIV in 2015 (n = 53) with data on interventions to prevent perinatal HIV transmission (eg, maternal HIV diagnosis before and during pregnancy and prenatal antiretroviral use). We also estimated the annual number of deliveries to women living with HIV by using the number of women of childbearing age living with HIV during 2008-2014 and the estimated birth rate among these women. Finally, we determined any changes in the annual number of infants born to women with HIV from 2007-2015, among 19 states that reported these data. RESULTS: The low number of infants born in the United States with HIV infection and the uptake of interventions to prevent perinatal HIV transmission were not consistent with the 2006 estimate (n = 8700), even with the best uptake of interventions to prevent perinatal HIV transmission. Given the birth rate among women with HIV (estimated at 7%) and the number of women aged 13-44 living with HIV during 2008-2014 (n = 111 273 in 2008, n = 96 363 in 2014), no more than about 5000 women with HIV would be giving birth. Among states consistently reporting the annual number of births to women with HIV, the number declined about 14% from 2008 to 2014. CONCLUSION: The current annual number of women with HIV infection delivering infants in the United States is about 5000, which is substantially lower than the 2006 estimate. More accurate estimates would require comprehensive reporting of perinatal HIV exposure.

OBJECTIVE: To examine HIV viral suppression during/after pregnancy. DESIGN: Prospective observational cohort. METHODS: We identified pregnancies from 1996 to 2015. We examined HIV RNA viral load (VL), VL suppression (</=500 copies/mL), and antiretroviral therapy (ART) status at pregnancy start, end, and 6 months postpartum. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for VL nonsuppression. RESULTS: Among 253 pregnancies analyzed, 34.8% of women exhibited VL suppression at pregnancy start, 60.1% at pregnancy end, and 42.7% at 6 months postpartum. Median VL (log10 copies/mL) was 2.80 (interquartile range [IQR]: 1.40-3.85) at pregnancy start, 1.70 (IQR: 1.40-2.82) at pregnancy end, and 2.30 (IQR: 1.40-3.86) at postpartum. Risk of postpartum VL nonsuppression was also lower among women on ART and with VL suppression at pregnancy end (versus those not; adjusted RR = 0.30, 95% CI: 0.17-0.53). CONCLUSIONS: Maintaining VL suppression among US women remains a challenge, particularly during postpartum. Achieving VL suppression earlier during pregnancy benefits women subsequently.

The influence of exposure duration on chemical toxicity has important implications for risk assessment. Although a default 10-fold extrapolation factor is commonly applied when the toxicological dataset includes a subchronic (90-day) study but lacks studies of chronic duration, little consensus has been reached on an appropriate extrapolation factor to apply when the dataset includes a 28-day study but lacks studies of longer durations. The goal of the present assessment was to identify a 28-day to 90-day extrapolation factor by analyzing distributions of ratios of No-Observed-Adverse-Effect Levels (NOAELs) and Benchmark Doses (BMDs) derived from 28-day and 90-day studies. The results of this analysis suggest that a default 10-fold extrapolation factor in chemical risk assessment applications is sufficient to account for the uncertainty associated with evaluating human health risk based on results from a 28-day study in the absence of results from a 90-day study. This analysis adds significantly to the growing body of literature interpreting the influence of exposure duration on chemical toxicity that will likewise facilitate discussions on the future state of testing requirements in the international regulatory community.

BACKGROUND: An incidence of perinatally acquired HIV infection less than 1:100,000 live births is one of the Centers for Disease Control and Prevention (CDC) goals of the United States. Such an estimate has only been possible in recent years because regular nationwide data were lacking. METHOD: Using previously published CDC estimates of the number of infants born with HIV infection in the United States (interpolating for years for which there was no published estimate), and census data on the annual number of live-born infants, estimated incidence was calculated for 1978-2013. Exact 95% confidence intervals (CIs) were calculated using the Poisson distribution. RESULTS: Estimated incidence of perinatally acquired HIV infection peaked at 43.1 (95% CI: 41.1 to 45.1) in 1992 and declined rapidly after the use of zidovudine prophylaxis was recommended in 1994. In 2013, estimated incidence of perinatally acquired HIV infection in the United States was 1.8 (95% CI: 1.4 to 2.2), a 96% decline since the peak. CONCLUSION: Estimated incidence of perinatally acquired HIV infection in the United States in 2013 was 1.8/100,000 live births.

BACKGROUND: Diagnoses of HIV infection among children in the United States (US) have been declining; however, a notable percentage of diagnoses are among those born outside the United States. The impact of foreign birth among children with diagnosed infections has not been examined in the United States. METHOD: Using the CDC National HIV Surveillance System, we analyzed data for children aged <13 years with diagnosed HIV infection ("children") in the United States (reported from 50 states and the District of Columbia) during 2008-2014, by place of birth and selected characteristics. RESULTS: There were 1,516 children (726 US-born [47.9%] and 676 foreign-born [44.6%]). US-born children accounted for 70.0% in 2008, declining to 32.3% in 2013, and 40.9% in 2014. Foreign-born children have exceeded US-born children in number since 2011.Age at diagnosis was younger for US-born than foreign-born children (0-18 months: 72.6% vs. 9.8%; 5-12 years: 16.9% vs. 60.3%). HIV diagnoses in mothers of US-born children were made more often before pregnancy (49.7% vs 21.4%), or during pregnancy (16.6% vs 13.9%), and less often after birth (23.7% vs 41%). Custodians of US-born children were more often biological parents (71.9% vs 43.2%), and less likely to be foster or non-related adoptive parents (10.4% vs 55.1%).Of 676 foreign-born children with known place of birth, 65.5% were born in sub-Saharan Africa and 14.3% in Eastern Europe. The top countries of birth were Ethiopia, Ukraine, Uganda, Haiti, and Russia. CONCLUSION: The increasing number of foreign-born children with diagnosed HIV infection in the United States requires specific considerations for care and treatment.

Existing U.S. guidelines recommend that men with human immunodeficiency virus (HIV) infection should achieve virologic suppression* with effective antiretroviral therapy (ART) before attempting conception. Clinical studies have demonstrated that effective ART profoundly reduces the risk for HIV transmission. This information might be useful for counseling couples planning a pregnancy in which the man has HIV infection and the woman does not (i.e., a mixed HIV-status couple, often referred to as a serodiscordant couple).

Importance: Perinatal transmission of human immunodeficiency virus (HIV) can be reduced through services including antiretroviral treatment and prophylaxis. Data on the national incidence of perinatal HIV transmission and missed prevention opportunities are needed to monitor progress toward elimination of mother-to-child HIV transmission. Objective: To estimate the number of perinatal HIV cases among infants born in the United States. Design, Setting, and Participants: Data were obtained from the National HIV Surveillance System on infants with HIV born in the United States (including the District of Columbia) and their mothers between 2002 and 2013 (reported through December 31, 2015). Estimates were adjusted for delay in diagnosis and reporting by weighting each reported case based on a model incorporating time from birth to diagnosis and report. Analysis was performed from April 1 to August 15, 2016. Exposures: Maternal HIV infection and antiretroviral medication, including maternal receipt prenatally or during labor/delivery and infant receipt postnatally. Main Outcomes and Measures: Diagnosis of perinatally acquired HIV infection in infants born in the United States. Infant and maternal characteristics, including receipt of perinatal HIV testing, treatment, and prophylaxis. Results: The estimated annual number of perinatally infected infants born in the United States decreased from 216 (95% CI, 206-230) in 2002 to 69 (95% CI, 60-83) in 2013. Among perinatally HIV-infected children born in 2002-2013, 836 (63.0%) of the mothers identified as black or African American and 243 (18.3%) as Hispanic or Latino. A total of 236 (37.5%) of the mothers had HIV infection diagnosed before pregnancy in 2002-2005 compared with 120 (51.5%) in 2010-2013; the proportion of mother-infant pairs receiving all 3 recommended arms of antiretroviral prophylaxis or treatment (prenatal, intrapartum, and postnatal) was 22.4% in 2002-2005 and 31.8% in 2010-2013, with approximately 179 (28.4%) (2002-2005) and 94 (40.3%) (2010-2013) receiving antiretroviral prophylaxis or treatment during pregnancy. Five Southern states (Florida, Texas, Georgia, Louisiana, and Maryland) accounted for 687 (38.0%) of infants born with HIV infection in the United States during the overall period. According to national data for live births, the incidence of perinatal HIV infection among infants born in the United States in 2013 was 1.75 per 100000 live births. Conclusions and Relevance: Despite reduced perinatal HIV infection in the United States, missed opportunities for prevention were common among infected infants and their mothers in recent years. As of 2013, the incidence of perinatal HIV infection remained 1.75 times the proposed Centers for Disease Control and Prevention elimination of mother-to-child HIV transmission goal of 1 per 100000 live births.

OBJECTIVE: Using published, nationally representative estimates, we calculated the total number of perinatally HIV-exposed and -infected infants born during 1978-2010, the number of perinatal HIV cases prevented by interventions designed for the prevention of mother-to-child transmission (PMTCT), and the number of infants exposed to antiretroviral drugs during the prenatal and intrapartum periods. DESIGN: We calculated the number of infants exposed to antiretroviral drugs since 1994, and the number of cases of mother-to-child HIV transmission prevented from 1994-2010 using published data. We generated confidence limits for our estimates by performing a simulation study. METHODS: Data were obtained from published, nationally-representative estimates from CDC. Model parameters included the annual numbers of HIV-infected pregnant women, the annual numbers of perinatally-infected infants, the annual proportions of infants exposed to antiretroviral drugs during the prenatal and intrapartum period, and the estimated mother-to-child transmission (MTCT) rate in the absence of preventive interventions. For the simulation study, model parameters were assigned distributions and we performed 1,000,000 repetitions. RESULTS: Between 1978 and 2010, an estimated 186,157 (95% CI: 185,312-187,003) HIV-exposed infants and approximately 21,003 (95% CI: 20.179-21,288) infected infants were born in the United States. Between 1994 and 2010, an estimated 124,342 (95% CI: 123,651-125,034) HIV-exposed infants were born in the U.S., and approximately 6,083 (95% CI: 5,931-6,236) infants were perinatally infected with HIV. During this same period about 100,207 (95% CI: 99,374-101,028) infants were prenatally exposed to antiretroviral drugs. As a result of PMTCT interventions, an estimated 21,956 (95% CI: 20,191-23,759) MTCT HIV cases have been prevented in the US since 1994. CONCLUSION: Though continued vigilance is needed to eliminate mother-to-child HIV transmission, PMTCT interventions have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(dagger) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease( section sign) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available.

We agree with Luzuriaga and Mofenson (Feb. 25 issue)1 that it is possible to contemplate the elimination of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in the United States and in resource-limited areas. To that end, the framework at the Centers for Disease Control and Prevention (CDC) for the elimination of mother-to-child transmission of HIV-1 in the United States uses two targets: an incidence of less than 1 case per 100,000 live births and a mother-to-child transmission rate of less than 1%.2 Regarding the rate of less than 1% that is attributed to the United States in the article, the authors cite data from the United Kingdom and Ireland.3 | Figure 1. | Rate of Perinatally Acquired HIV Infection, According to Year of Birth and Maternal Race or Ethnic Group, 2008–2012. | Lacking a regular determination of the number of HIV-infected women who deliver infants in the United States, the national rate of mother-to-child transmission (2.2%) was last estimated with the use of the Enhanced Perinatal Surveillance data from the CDC for the period 2005–2008.4 The incidence of perinatal HIV-1 infection declined from 4.0 cases per 100,000 live births (in 2008) to 3.1 cases per 100,000 live births (in 2012) but with striking disparities among racial and ethnic groups: the rate was 15.1 cases per 100,000 live births among black infants, 1.7 per 100,000 live births among Hispanic infants, and 0.3 per 100,000 live births among white infants (Figure 1).5 Before and after meeting the targets for the elimination of mother-to-child transmission of HIV-1 for the United States as a whole, we must focus attention and resources on strategies to reduce the high rates of perinatal HIV infection in racial and ethnic minority populations.

Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC's national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(dagger) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),( section sign) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.

BACKGROUND: Concerns remain regarding the cancer risk associated with perinatal ARV exposure among infants. No excessive cancer risk has been found in short-term studies. METHOD: Children born to HIV-infected women (HIV-exposed) in New Jersey from 1995 to 2008 were identified through the Enhanced HIV/AIDS Reporting System (eHARS) and cross-referenced with data from the New Jersey State Cancer Registry to identify new cases of cancer among children who were perinatally exposed to ARV. Matching of individuals in eHARS to the New Jersey State cancer registry was conducted based on name, birthdate, Social Security number, residential address, and sex using AUTOMATCH. Age- and sex-standardized incidence ratio (SIR) and exact 95% confidence intervals (CI) were calculated using New Jersey (1979-2005) and United States (1999-2009) cancer rates. RESULTS: Among 3,087 children (29,099 person-years; 9.8 years median follow-up), four were diagnosed with cancer. Cancer incidence among HIV-exposed children who were not exposed to ARV prophylaxis (22.5 per 100,000 person-years) did not differ significantly from the incidence among children who were exposed to any perinatal ARV prophylaxis (14.3 per 100,000 person-years). Furthermore, the number of cases observed among individuals exposed to ARV did not differ significantly from cases expected based on state (SIR = 1.21; 95% CI, 0.25-3.54) and national (SIR = 1.27; 95% CI, 0.26-3.70) reference rates. CONCLUSION: Our findings are reassuring that current use of ARV for perinatal HIV prophylaxis does not increase cancer risk. We found no evidence to alter the current federal guidelines of 2014 that recommend ARV prophylaxis of HIV-exposed infants.

PURPOSE OF REVIEW: To describe progress and challenges to elimination of mother-to-child HIV transmission (EMCT) in high-income countries. RECENT FINDINGS: Despite ongoing declines in the number of perinatally HIV-infected infants in most high-income countries, the number of HIV-infected women delivering may be increasing, accompanied by apparent changes in this population, including higher percentages with antiretroviral 'pretreatment' (with possible antiretroviral resistance), other coinfections, mental health diagnoses, and recent immigration. The impact of antiretroviral resistance on mother-to-child transmission is yet to be defined. A substantial minority of infant HIV acquisitions occurs in the context of maternal acute HIV infection during pregnancy. Some infant infections occur after pregnancy, for example, by premastication of food, or breastfeeding (perhaps by an uninfected woman who acquires HIV while breastfeeding). SUMMARY: The issues of EMCT are largely those of providing proper care for HIV-infected women. Use of combination ART by increasing proportions of the infected population may function as a structural intervention important to achieving this goal. Providers and public health systems need to be alert for HIV-serodiscordant couples in which the woman is uninfected and for changes in the population of HIV-infected pregnant women. Accurate data about HIV-exposed pregnancies are vital to monitor progress toward EMCT.

The availability of effective interventions to prevent mother-to-child HIV transmission and the significant reduction in the number of HIV-infected infants in the United States have led to the concept that elimination of mother-to-child HIV transmission (EMCT) is possible. Goals for elimination are presented. We also present a framework by which elimination efforts can be coordinated, beginning with comprehensive reproductive health care (including HIV testing) and real-time case-finding of pregnancies in HIV-infected women, and conducted through the following: facilitation of comprehensive clinical care and social services for women and infants; case review and community action; allowing continuous quality research in prevention and long-term follow-up of HIV-exposed infants; and thorough data reporting for HIV surveillance and EMCT evaluation. It is emphasized that EMCT will not be a one-time accomplishment but, rather, will require sustained effort as long as there are new HIV infections in women of childbearing age.

OBJECTIVE: A 2004 national survey of hospitals showed that 23.4% of hospitals screened for HIV in at least one department, most frequently in labor and delivery departments. However, less than 2% of these hospitals screened patients in inpatient units, urgent care clinics, or emergency departments. In 2006, the Centers for Disease Control and Prevention (CDC) recommended HIV screening for all individuals 13-64 years of age in health-care settings. We determined the frequency of hospital adoption of these CDC recommendations. METHODS: We surveyed hospital infection-control personnel at a randomly selected sample of U.S. general medical and surgical hospitals in 2009-2010. RESULTS: Of the 1,476 hospitals selected for the survey, 754 (51.1%) responded to the survey; of those responding, 703 (93.2%) offered HIV tests for patients at the hospital and 206 (27.3%) screened for HIV in at least one department. Screening was most common in larger hospitals (45.7%), hospitals in large metropolitan areas (50.5%), and teaching hospitals (44.4%); it was least common in public hospitals (19.1%). By department, screening was most common in labor and delivery departments (34.6%) and substance abuse clinics (20.7%); it was least common in emergency departments (11.9%), inpatient units (9.6%), and psychiatry/mental health departments (9.4%). More than half of hospitals were not considering implementing CDC's recommendations within the next 12 months. CONCLUSIONS: Since 2004, HIV screening in hospitals increased overall and by department. However, the majority of U.S. hospitals have not adopted the CDC recommendations.

OBJECTIVE: The goal of this study was to examine associations between demographic, behavioral, and clinical variables and mother-to-child HIV transmission in 15 US jurisdictions for birth years 2005 through 2008. METHODS: The study used Enhanced Perinatal Surveillance system data for HIV-infected women who gave birth to live infants. Multivariable logistic regression was used to assess variables associated with mother-to-child transmission. RESULTS: Among 8054 births, 179 infants (2.2%) were diagnosed with HIV infection. Half of the births had at least 1 missed prevention opportunity: 74.3% of infected infants, 52.1% of uninfected infants. Among 7757 mother-infant pairs with sufficient data for analysis, the odds of having an HIV-infected infant were higher for women who received late testing or no prenatal antiretroviral medications (odds ratio: 2.5 [95% confidence interval (CI): 1.5-4.0] and 3.5 [95% CI: 2.0-6.4], respectively). The odds for mothers who breastfed were 4.6 times (95% CI: 2.2-9.8) the odds for those who did not breastfeed. The adjusted odds for women with CD4 counts <200 cells per microliter were 2.4 times (95% CI: 1.4-4.2) those for women with CD4 counts ≥500 cells per microliter. The odds for women who abused substances were twice (95% CI: 1.4-2.9) those for women who did not. CONCLUSIONS: The odds of having an HIV-infected infant were higher among HIV-infected women who were tested late, had no antiretroviral medications, abused substances, breastfed, or had lower CD4 cell counts. Increases in earlier HIV diagnosis, substance abuse treatment, avoidance of breastfeeding, and use of prenatal antiretroviral medications are critical in eliminating perinatal HIV infections in the United States.

Approximately half of HIV-discordant heterosexual couples in the United States want children. Oral antiretroviral preexposure prophylaxis, if effective in reducing heterosexual HIV transmission, might be an option for discordant couples wanting to conceive. Couples should receive services to ensure they enter pregnancy in optimal health and receive education about all conception methods that reduce the risk of HIV transmission. In considering whether preexposure prophylaxis is indicated, the question is whether it contributes to lowering risk in couples who have decided to conceive despite known risks. If preexposure prophylaxis is used, precautions similar to those in the current heterosexual preexposure prophylaxis trials would be recommended, and the unknown risks of preexposure prophylaxis used during conception and early fetal development should be considered. Anecdotal reports suggest that oral preexposure prophylaxis use is already occurring. It is time to have open discussions of when and how preexposure prophylaxis might be indicated for HIV-discordant couples attempting conception.

OBJECTIVE: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). DESIGN: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. METHODS: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. RESULTS: HIV prevalence was 0.06% among 921,438 pregnant women and 1.34% among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14% vs. 0.21%, odds ratio 0.65 [95% confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p<0.01) to have Western blot-negative (52.9% vs. 9.8%) and indeterminate results (17.0% vs. 3.7%) and lower PPV (30% vs. 87%). The p24 band was detected more often among pregnant women (p<0.01). CONCLUSIONS: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others. Pregnant women with reactive EIAs were more likely to have negative and indeterminate Western blot results due to lower HIV prevalence and higher p24 reactivity, respectively. Indeterminate results may complicate clinical management during pregnancy. Alternative methods are needed to rule out infection in persons with reactive EIAs from low prevalence populations.