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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: 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.

Purpose of Review: Because of widespread availability of highly active antiretroviral therapy in the developed world, a large proportion of children with perinatally acquired HIV have survived to adolescence and young adulthood. Although their survival is remarkable, many now experience the long-term effects of HIV infection and its treatment. Further, as these youths have entered adolescence, more is known about the impact of normative developmental transitions on health maintenance behaviors., Recent Findings: Although perinatally infected adolescents are healthier than they were a decade or more ago, they are significantly experienced with antiretroviral therapy, with increased virological resistance and other consequences of extended antiretroviral use. Three behavioral health challenges have been documented in the first cohort of long-term survivors: decreased medication adherence, sexual debut and accompanying pregnancy and transmission risk, and mental health problems. These issues are consistent with a developmental press for autonomy, mature sexual relationships and future planning, but must be carefully managed to preserve health., Summary: Adolescents with perinatally acquired HIV require coordinated multidisciplinary support services - including adherence support, reproductive health counseling addressing both pregnancy planning and disease transmission, and mental health and educational/vocational planning - so that they can fully benefit from treatment advances., ((C) 2011 Lippincott Williams & Wilkins, Inc.)

This article covers HIV drug resistance among pregnant women and the implications of transmission of resistant HIV to the infant. Resistance to antiretroviral drugs may be acquired or can emerge while HIV-infected pregnant women are on antiretroviral therapy, either before or during pregnancy. Resistance to antiretroviral drugs among HIV-infected infants may be acquired from the mother in utero or during the intrapartum period. Resistance may also emerge from exposure to antiretroviral drugs given to the infant for prophylaxis against HIV transmission. In settings where breastfeeding is practiced, ongoing transmission of HIV from breastfeeding may lead to transmission of resistant HIV from the mother. If the mother is taking antiretroviral drugs while breastfeeding, resistance to antiretroviral drugs may emerge in an HIV-infected infant from ingestion of antiretroviral drugs via breast milk. The magnitude and implications of antiretroviral resistance among HIV-infected pregnant women and HIV-infected infants are summarized., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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: To determine the relationship of maternal health factors and infant antiretroviral treatment to the risk of pediatric disease progression to AIDS or death by 24 months of age., Design: Prospective perinatal HIV-1 transmission and pediatric natural history study., Setting: Urban medical centers in four cities in the USA., Participants: A total of 2656 pregnant and postpartum HIV-infected women enrolled in the Perinatal AIDS Collaborative Transmission Study (PACTS) and 360 children determined to be HIV-infected., Main Outcome Measures: Pediatric AIDS or death by 24 months of age., Results: Children born to mothers with class C disease, CD4 cell count < 200 x 106/l, or HIV-1 RNA viral load > 100 000 copies/ml progressed more rapidly than children born to mothers with less advanced disease. In a multivariate analysis, there was an increased risk of progression if mothers had Class C disease [relative risk (RR), 1.7; 95% confidence interval (CI), 1.0-2.7] or HIV-1 RNA > 100 000 copies/ml (RR, 2.4; 95% CI, 1.2-4.6) controlling for child antiretroviral therapy and year of birth. Earlier years of birth significantly increased the likelihood of rapid progression (P = 0.01) in this multivariate model. Children who received combination antiretroviral therapies with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor were significantly less likely to progress compared with those receiving no therapy (P = 0.03)., Conclusions: HIV-1-infected infants born to women with advanced HIV-1 disease were at increased risk for rapid disease progression. More recent birth year and early treatment with potent antiretroviral therapy significantly diminished the likelihood of developing AIDS or dying during early childhood.

Women enrolled in prenatal care at Grady Health System, Atlanta, GA, have routinely been offered HIV counseling and voluntary testing since 1987. Consistently >90% have accepted testing. With implementation of US Public Health Service guidelines for perinatal zidovudine prophylaxis in 1994, the mother-to-child HIV transmission rate rapidly decreased from 18% to 8% during the subsequent 2 years.

To assess the impact of antiretroviral resistance on perinatal transmission prevention efforts, human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing was done for 220 HIV-1-infected, zidovudine (AZT)-exposed pregnant women and 24 of their infected infants. The women were prospectively enrolled in 4 US cities in 1991-1997. Phylogenetic and sequencing analyses revealed 5 women with non-clade B infections traced to western African origins. AZT-associated mutations were detected in 17.3% of pregnant women, whereas genotypic resistance to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors was infrequent. No significant association was detected between perinatal transmission and the presence of either AZT or nucleoside reverse-transcriptase inhibitor resistance-associated mutations. AZT resistance mutations were detected in 2 (8.3%) neonatal samples, but the mutation pattern was not identical to the mother's. Although no effect of viral resistance on mother-infant transmission was demonstrated, the advent of more-potent drug classes and the potential for the rapid emergence of resistance warrant prospective surveillance.

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.

Objectives: To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine., Design: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities., Methods: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics., Results: The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors., Conclusions: Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

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.