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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 † (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. § 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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

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 (log 10 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.

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.

The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine rapid HIV testing in labor and delivery (L&D) for women with undocumented HIV status using an opt-out approach. Identifying factors associated with declining a rapid HIV test in L&D will be helpful in developing strategies to improve rapid HIV testing uptake. Data from the Mother-Infant Rapid Intervention at Delivery study were analyzed. Women ≥24 weeks gestation, in labor, with undocumented HIV status were offered rapid HIV testing using informed consent. Women who declined rapid HIV testing (decliners) but agreed to be interviewed were compared to women who accepted testing (acceptors). 102 decliners and 478 acceptors met inclusion criteria for analysis. Decliners of rapid HIV testing were more likely to have had prenatal care (PNC), after adjusting for age, Hispanic ethnicity, high-school education and city of enrollment (adjusted OR 2.4, 95% CI 1.06-5.58). Having had PNC was collinear with prior HIV education and previous offer of an HIV test during the current pregnancy, so these factors were not part of the model. During PNC, standard informed consent may involve discussions that negatively affect later uptake of testing in L&D. Therefore an opt-out approach to testing may improve testing rates. Furthermore, decliners may have felt that testing in L&D was redundant because of previous testing during PNC; however, if previous testing occurred, this was undocumented at L&D. Documentation and timely communication of HIV status is critical to provide appropriate HIV prophylaxis.

Objective: To determine if women with undocumented HIV status in late pregnancy or at labor and delivery who are rapidly tested and identified as HIV infected have high-risk behaviors and psychosocial obstacles hindering postpartum follow-up., Methods: Consenting participants (women with undocumented HIV status and > or =24 weeks gestational age (GA) and imminent delivery or > or =34 weeks GA) in 6 cities were rapidly tested and interviewed. HIV-positive women were offered follow-up., Results: From 2001-2005, 54 HIV-infected women were identified: median age 26 years; 91% African American; 11 (20%) lost custody of their infants; 30 (56%) knew they or their partner were HIV-infected, but had no antenatal HIV care; 25 met criteria for starting antiretroviral therapy. Comparison between 48 HIV-infected and 130 HIV-negative women, tested and interviewed at the same hospitals, showed HIV-infected women more likely to be African American (P < .01) and report no prenatal care (P < .001), use street drugs (P < .01), have unstable residency (P < .05), not live with the father of their infant (P < .001), and have children in foster care (P < .01). Sixteen women (30%) and 17 (31%) infants did not remain in follow-up study due to relocation, child protective custody, and psychosocial issues including frequent substance use., Conclusion: Over half of HIV-infected women knew they or their partner were infected with HIV, but did not initially disclose their status. Increased support services and substance abuse treatment are critical to facilitate better continuity of care for these socially marginalized women.

Objective: To determine factors associated with prenatal HIV testing in women who accepted rapid testing at delivery., Methods: The mother-infant rapid intervention at delivery (MIRIAD) protocol offered counseling and voluntary HIV testing in six US cities including New York City (NYC). These hospitals are required to document the HIV status of pregnant women or their infants. From January 2002 to January 2005, 653 HIV-negative women were interviewed post-partum., Results: 63% of women reported prior HIV testing during the index pregnancy, although their results were not available at delivery. Multivariate logistic modeling identified receipt of prenatal care and delivery in NYC as being associated with having been offered prenatal HIV testing. In a model restricted to women receiving medical care, emergency department (ED) use and delivery outside of NYC were associated with not having been offered testing. In a model restricted to women who were offered prenatal testing, acceptance was associated with delivery outside of NYC., Conclusions: Improved documentation of prenatal test results, expanded prenatal testing in non-traditional settings like EDs, and routine voluntary "opt-out" testing during pregnancy may further reduce perinatal HIV transmission.

Objective: The purpose of this study was to describe characteristics of pregnant women with newly acquired human immunodeficiency virus (HIV) infection that was identified by repeat testing., Study Design: The Centers for Disease Control and Prevention-sponsored Mother-Infant Rapid Intervention at Delivery (MIRIAD) study, which was conducted in 6 US cities, encouraged repeat HIV testing during pregnancy to identify primary infections., Results: Fifty-four HIV-infected women were identified. Four primary HIV infections were recognized, with median estimated seroconversion at 22 weeks of gestation. All 4 women denied new sex partners, alcohol, and illegal drug use during pregnancy. Three of the 4 mother-infant pairs received antiretroviral medications. One infant was infected perinatally, with positive HIV DNA polymerase chain reaction at birth. Questionnaire data identified 2 additional women with HIV that was likely acquired during pregnancy (identified by rapid testing at labor and delivery), which suggests that 6 of 54 HIV-infected women (11%) in the MIRIAD study had primary infection during pregnancy., Conclusion: Repeat HIV testing in pregnancy can identify opportunities for antiretroviral prophylaxis and should be used in areas of high HIV prevalence.

Recently, we developed an immunoglobulin G (IgG)-capture BED-enzyme immunoassay (BED-CEIA) to identify recent HIV-1 infections. We estimated HIV-1 incidence among inner-city pregnant women in Atlanta, Georgia (1991-1998) using this assay. The annual cumulative incidence was estimated at 2.4/1000 (95% CI = 2.0-2.9). Incidence declined from 3.1/1000 in 1991-1994 to 1.4/1000 in 1995-1998 (risk ratio = 2.3, 95% CI = 1.5-3.4). Women with recent HIV-1 infection more often reported a previous negative antibody test (p = 0.018) and sexual relations with men other than the father during the past year (p = 0.046). Fewer seroconverters in 1995-1998 used crack cocaine than in the earlier time period. A high but declining HIV-1 incidence was found among inner-city pregnant women in Atlanta.

Context: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis., Objectives: To determine the feasibility and acceptance of rapid HIV testing among women in labor and to assess rapid HIV assay performance., Design, Setting, and Patients: The Mother-Infant Rapid Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and voluntary rapid HIV testing for women in labor at 16 US hospitals from November 16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood was used., Main Outcome Measures: Acceptance of HIV testing; sensitivity, specificity, and predictive value of the rapid test; time from blood collection to patient notification of results., Results: There were 91,707 visits to the labor and delivery units in the study, 7381 of which were by eligible women without documentation of HIV testing. Of these, 5744 (78%) women were approached for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test were 100% and 99.9%, respectively; positive predictive value was 90% compared with 76% for enzyme immunoassay (EIA). Factors independently associated with higher test acceptance included younger age, being black or Hispanic, gestational age less than 32 weeks, and having had no prenatal care. Lower acceptance was associated with being admitted between 4 pm and midnight, particularly on Friday nights, but this may be explained in part by fewer available personnel. Median time from blood collection to patient notification of result was 66 minutes (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001)., Conclusions: Rapid HIV testing is feasible and delivers accurate and timely test results for women in labor. It provides HIV-positive women prompt access to intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal HIV transmission, and may be particularly applicable to higher-risk populations.

Background: Although increasing attention has been focused on the adequacy of the informed consent process for participation in research studies, there has been little systematic evaluation of the process, particularly when consent is obtained in the labor and delivery setting. The Mother Infant Rapid Intervention at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers for Disease Control and Prevention (CDC) designed to evaluate the feasibility of offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral therapy when indicated to women with unknown HIV status who are in labor., Methods: To address concerns about obtaining informed consent from women in labor, we have completed focus groups, conducted a pilot of the informed consent process among women in labor, developed flip-charts to enhance comprehension, and plan an ongoing evaluation of the informed consent process throughout the course of the MIRIAD study., Results: In the pilot study, approximately 70% of women were able to state in their own words the purpose and benefits of the research study. Substantially fewer women (25%) were able to state one or more risks of the study., Conclusions: We hope that the MIRIAD study will make a valuable contribution by defining best approaches for informed consent and will provide guidance when it is necessary to obtain consent from laboring women for crucial interventions.

Objectives: To evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV-infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV., Design/methods: The Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother-to-child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998., Results: Utilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4-year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother-infant pairs with the following characteristics were less likely to have received a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/microl, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6-3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2-0.8; comparing <200 with >500 cells/microl), and preterm birth (OR, 1.6; 95% CI, 1.1-2.5) remained independently associated with not receiving the complete ZDV regimen., Conclusions: ZDV use by pregnant HIV-infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.

A recent report suggesting mitochondrial dysfunction among eight HIV-exposed but uninfected children exposed perinatally to nucleoside reverse transcriptase inhibitors (NRTIs) prompted a review within the Perinatal AIDS Collaborative Transmission Study (PACTS). A standardized retrospective review was conducted of 118 deaths at < 5 years. Deaths were classified as unrelated to mitochondrial dysfunction (Class 1), unlikely related (Class 2), possibly related (Class 3), or likely related or proven (Class 4). Among 35 deaths recorded in HIV-uninfected or indeterminate children, none were classified in either Class 2, 3, or 4. We also reviewed signs or symptoms consistent with possible mitochondrial dysfunction among 1,954 living uninfected children. Only one child was in Class 3 and two siblings were in Class 2; none had perinatal antiretroviral drug exposure. We found no evidence indicating that uninfected infants exposed to perinatal NRTIs died of mitochondrial disorders or that living exposed children had symptoms of mitochondrial dysfunction.

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Along with increasing knowledge of factors that put infants at risk for mother-to-infant HIV transmission (e.g., maternal-viral load, HIV-disease state, prematurity, and prolonged membrane rupture), there are new approaches to reducing the likelihood of such transmission (e.g., zidovudine treatment). Additional means of reducing transmission may become available in years to come. In this context, prenatal voluntary identification of HIV-infected women is vital. Finally, appropriate use of early diagnostic tests in HIV-exposed infants will allow effective use of prophylactic and therapeutic means.

Background: Little is known about whether a woman's risk of transmitting HIV perinatally increases over time and whether the infection outcome of a previous child affects the risk of transmitting HIV to subsequent children., Methods: We analyzed data from 114 prospectively followed women who gave birth to at least 2 children after becoming infected with HIV to determine the risk for perinatal HIV transmission to these sibling pairs., Results: The median interval between sibling births was 19 months. HIV infection occurred in 19 (17%) older siblings and 20 (18%) younger siblings (P = 0.87). Two (11%) of the 19 children with infected older siblings were infected compared with 18 (19%) of the 95 children with uninfected older siblings (P = 0.86). The risk for transmission to younger siblings was not associated with the interval between deliveries of the two siblings., Conclusions: These data do not demonstrate that an HIV-infected woman's risk of transmitting HIV perinatally increases with time, although the observed interpregnancy interval was relatively short. The risk for perinatal transmission does not appear to be affected by the infection outcome of previous children. These findings may be useful for counseling HIV-infected women about their risk of transmitting HIV perinatally.