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OBJECTIVE. We sought to determine the impact of highly active antiretroviral therapy on the incidence and prevalence of opportunistic infections in HIV-infected children. METHODS. Children born from 1986 to 1998 were monitored until 2004 in the Perinatal AIDS Collaborative Transmission Study, sponsored by the Centers for Disease Control and Prevention. We determined the pre-highly active antiretroviral therapy and post-highly active antiretroviral therapy (before and after January 1, 1997, respectively) incidence rates of opportunistic infections among HIV-infected children and characterized the temporal decreases in percentages of CD4(+) cells and the mortality rates among patients with and those without incident opportunistic infections. RESULTS. The overall opportunistic infection incidence declined from 14.4 to 1.1 cases per 100 patient-years; statistically significant reductions were seen in the incidence of the most common opportunistic infections, including Pneumocystis jiroveci pneumonia (5.8 vs 0.3 cases per 100 patient-years), recurrent bacterial infections (4.7 vs 0.2 cases per 100 patient-years), extraocular cytomegalovirus infection (1.4 vs 0.1 cases per 100 patient-years), and disseminated nontuberculous mycobacterial infection (1.3 vs 0.2 cases per 100 patient-years). Kaplan-Meier analysis of time from birth to the first opportunistic infection illustrated more-rapid acquisition of opportunistic infections by HIV-infected children born in the pre-highly active antiretroviral therapy era than by those born later. In the first 3 years of life, there was a faster decline in the percentage of CD4(+) cells among children with opportunistic infections. The mortality rate was significantly higher among children with opportunistic infections. CONCLUSIONS. Reduction in the incidence of opportunistic infections and prolongation of the time to the first opportunistic infection were noted during the post-highly active antiretroviral therapy era. Children who experienced opportunistic infections had higher mortality rates than did those who did not. Younger children (<3 years) who experienced opportunistic infections had faster declines in percentages of CD4(+) T cells. [ABSTRACT FROM AUTHOR]

Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency virus transmission (HIV), but its consequences for disease progression among children infected despite Zdv exposure remain unknown. In a multicenter observational cohort study of 325 HIV-infected children born during 1986-1997, clinical progression was compared among infected children exposed or unexposed to Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8-fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS or death after adjusting for year of birth, maternal CD4 cell count, maternal AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10) viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No infected child treated early with multidrug therapy progressed to AIDS or died by 1 year, regardless of early Zdv exposure. More rapid disease progression was observed among infected children exposed during pregnancy or birth to Zdv if effective multidrug therapy was not initiated. Copyright © 2000 The University of Chicago [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Abstract: 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.

Objectives: Retention in care is a critical component of effective HIV treatment, and adolescents and young adults are at higher risk of inadequate retention than older adults. The objective of our study was to examine the patterns of retention in care among adolescents and young adults with HIV infection by analyzing Medicaid and commercial health insurance claims data., Methods: We evaluated retention in care for HIV-diagnosed adolescents and young adults aged 13-24 using the 2010-2014 MarketScan Medicaid and MarketScan Commercial Claims health insurance databases. The study period extended 36 months from the date of the first claim with a code for HIV or AIDS. We determined the unweighted proportion retained in care for the Medicaid and Commercial Claims cohorts for months 0-24 and 25-36. We assessed associations between demographic characteristics and retention in care using logistic regression., Results: A total of 378 adolescents and young adults were in the Medicaid cohort and 1028 in the Commercial Claims cohort. In the Medicaid and Commercial Claims cohorts, respectively, 186 (49%) and 591 (57%) adolescents and young adults were retained in care during months 0-24. In the Medicaid cohort, 113 (73%) people retained in care and 69 (45%) people not retained in care during months 0-24 were retained in care during months 25-36. In the Commercial Claims cohort, 313 (77%) and 94 (31%) retained and not retained people, respectively, were found to be in care during months 25-36., Conclusions: Notable proportions of HIV-diagnosed adolescents and young adults are not adequately retained in care; public health interventions tailored to this population are needed.

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 with those among US-born children for all OIs except tuberculosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

Background: Medical advancements have improved the survival of persons with perinatally acquired HIV infection (PHIV). We describe persons living with diagnosed PHIV and assess receipt of HIV care, retention in care, and viral suppression., Methods: Data reported to the National HIV Surveillance System through December 2017 were used to characterize persons living with diagnosed PHIV by year-end 2015 in the United States and 6 dependent areas. National HIV Surveillance System data from 40 jurisdictions with complete laboratory reporting were used to assess receipt of HIV care (≥1 CD4 or viral load during 2015), retention in HIV care (≥2 CD4 or viral load tests ≥3 months apart during 2015) and viral suppression (<200 copies/mL during 2015) among persons with PHIV diagnosed by year-end 2014 and alive at year-end 2015., Results: By year-end 2015, 11,747 persons were living with PHIV and half were aged 18-25 years. Of 9562 persons with HIV diagnosed by year-end 2014 and living with PHIV at year-end 2015 in the 40 jurisdictions, 75.4% received any care, 61.1% were retained in care, and 49.0% achieved viral suppression. Persons aged ≤17 years had a significantly higher prevalence of being retained in care (prevalence ratio = 1.2, 95% confidence interval = 1.2 to 1.3) and virally suppressed (prevalence ratio = 1.4, 95% confidence interval = 1.3 to 1.5) than persons aged 18-25 years., Conclusions: Efforts to improve care outcomes among persons with PHIV are needed. Enhanced collaboration between pediatric and adult medical providers may ensure continuity of care during the transition from adolescence to adulthood.

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 born with HIV 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 transmission 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 before pregnancy and breast-feeding 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 (8700) 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.

The Centers for Disease Control and Prevention and the American Congress of Obstetricians and Gynecologists recommend universal prenatal HIV testing to prevent perinatal HIV transmission in the U.S.; since the 1990s perinatal HIV transmission has declined. In 2006, 74% of women with a recent live birth reported testing for HIV prenatally or at delivery. We used Pregnancy Risk Assessment Monitoring System data from 36 states and New York City from 2004 to 2013 (N = 387,424) to assess characteristics associated with lack of self-reported testing and state-to-state variability in these associations. Overall, 75.2% (95% confidence interval [CI] 75.0-75.5) of women with a recent live birth reported an HIV test. There were significant differences in testing prevalence by state, ranging from 91.8% (95% CI 91.0-92.6) in New York to 42.3% (95% CI 41.7-43.5) in Utah. In adjusted analysis, characteristics associated with no reported testing included being married, white, non-Hispanic, multiparous, not smoking during pregnancy, and having neither Medicaid nor Special Supplemental Nutritional Program for Women, Infants, and Children. White married women were 57% (adjusted prevalence ratio [aPR] 1.57, 95% CI 1.52-1.63) more likely to report no test compared to white unmarried women. Multiparous married women were 57% (aPR 1.57, 95% CI 1.51-1.64) more likely to report no test compared to multiparous unmarried women. Women who were married, white, non-Hispanic, and multiparous women were 23% less likely to be tested than other women combined. Marital status was significantly associated with lower prevalence of testing in 35 of the 37 reporting areas, and race was significant in 30 of 35 states with race information. The prevalence of reported HIV testing during pregnancy or at delivery remains below 80%. Opportunities exist to increase HIV testing among pregnant women, particularly among certain subpopulations.

Objective: This study aimed to analyze prenatal human immunodeficiency virus (HIV) testing rates over time and describe the impact of state HIV testing laws on prenatal testing., Methods: During 2004-2011, self-reported prenatal HIV testing data for women with live births in 35 states and New York City were collected. Prevalence of testing was estimated overall and by state and year. An annual percent change was calculated in states with at least 6 years of data to analyze testing changes over time. An attorney-coder used WestlawNext to identify states with laws that direct prenatal care providers to screen all pregnant women or direct all women to be tested for HIV and document changes in laws to meet this threshold., Results: The overall prenatal HIV testing rate for 2004 through 2011 combined was 75.7%. State-level data showed a wide range of testing rates (43.2%-92.8%) for 2004 through 2011 combined. In areas with 6 years of data, 4 experienced an annual drop in testing (Alaska, Arkansas, Colorado, and Illinois). States that changed laws to meet the threshold generally had the highest testing rates, averaging 80%, followed by states with a preexisting law, at approximately 70%. States with no law, or no law meeting the threshold, had an average prenatal testing rate of 65%., Conclusions: Prenatal HIV testing remained stable between 2004 and 2011 but remained below universal recommendations. Testing varied widely across states and was generally higher in areas that changed their laws to meet the threshold or had preexisting prenatal HIV testing laws, compared with those with no or limited prenatal HIV testing language.

Background: Diagnoses of HIV infection among children in the United States 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., Methods: Using the Centers for Disease Control and Prevention 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 1516 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 nonrelated 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., Conclusions: The increasing number of foreign-born children with diagnosed HIV infection in the United States requires specific considerations for care and treatment.

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.

In 2014, an estimated 2,477 children aged <13 years were living with diagnosed human immunodeficiency virus (HIV) infection in the United States (1). Nationally, little is known about how well children with a diagnosis of HIV infection are retained in medical care. CDC analyzed insurance claims data to evaluate retention in medical care for children in the United States with a diagnosis of HIV infection. Data sources were the 2010-2014 MarketScan Multi-State Medicaid and MarketScan Commercial Claims and Encounters databases. Children aged <13 years with a diagnosis of HIV infection in 2010 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic billing codes for HIV or acquired immunodeficiency syndrome (AIDS), resulting in Medicaid and commercial claims cohorts of 163 and 129 children, respectively. Data for each child were evaluated during a 36-month study period, counted from the date of the first claim containing an ICD-9-CM code for HIV or AIDS. Each child's consistency of medical care was assessed by evaluating the frequency of medical visits during the first 24 months of the study period to see if the frequency of visits met the definition of retention in care. Frequency of medical visits was then assessed during an additional 12-month follow-up period to evaluate differences in medical care consistency between children who were retained or not retained in care during the initial 24-month period. During months 0-24, 60% of the Medicaid cohort and 69% of the commercial claims cohort were retained in care, among whom 93% (Medicaid) and 85% (commercial claims) were in care during months 25-36. To identify areas for additional public health action, further evaluation of the objectives for national medical care for children with diagnosed HIV infection is indicated.

Timely linkage to HIV care (LTC) following an HIV diagnosis is especially important for pregnant women with HIV to prevent perinatal transmission and improve maternal health. However, limited data are available on LTC among U.S. pregnant women. Our analysis aimed to identify HIV diagnoses among childbearing age (CBA) women (15-44 years old) by pregnancy status and to compare LTC of HIV-infected pregnant women to HIV-infected non-pregnant women. We analyzed 2013 CDC-funded HIV testing data from 61 health departments and 151 directly funded community-based organizations among CBA women. LTC includes linkage at any time after an HIV diagnosis and within 90 days after HIV diagnosis. Pearson's chi-square was used to compare LTC of pregnant and non-pregnant women. Data were analyzed using SAS v9.3. Among the 1,379,860 HIV testing events among CBA women in 2013, 0.3% (n = 3690) were HIV-positive. Among all HIV-positive diagnoses with an available pregnancy status (n = 1987), 7%, (n = 138) were pregnant. Among women with pregnancy status data, LTC any time after an HIV-positive diagnosis was 73.2% for pregnant women and 60.7% for non-pregnant women. LTC within 90 days was 71.7% for pregnant women and 56.2% for non-pregnant women. Pregnancy was associated with LTC any time (p < 0.01) and within 90 days of diagnosis (p < 0.01). Compared with non-pregnant women, a higher proportion of pregnant women with HIV were linked to care overall, and linked within 90 days. Pregnancy appears to facilitate better LTC, but improvements are needed for women overall and pregnant women specifically.

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 100 000 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 100 000 live births.

Objectives: Using published, nationally-representative estimates, we calculated the total number of perinatally HIV-exposed and HIV-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 (ARV) drugs during the prenatal and intrapartum periods., Design: We calculated the number of infants exposed to ARV drugs since 1994, and the number of cases of mother-to-child HIV transmission prevented from 1994 to 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 the Centers for Disease Control and Prevention. 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 ARV drugs during the prenatal and intrapartum period and the estimated 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% confidence interval (CI): 185,312-187,003] HIV-exposed infants and approximately 21,003 (95% CI: 20,179-21,288) HIV-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 US, and approximately 6083 (95% CI: 5931-6236) infants were perinatally infected with HIV. During this same period, about 100,207 (95% CI: 99,374-101,028) infants were prenatally exposed to ARV 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 United States since 1994., Conclusion: Although 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.

Background: Concerns remain regarding the cancer risk associated with perinatal antiretroviral (ARV) exposure among infants. No excessive cancer risk has been found in short-term studies., Methods: Children born to HIV-infected women (HIV-exposed) in New Jersey from 1995 to 2008 were identified through the Enhanced HIV/AIDS Reporting System 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 the Enhanced HIV/AIDS Reporting System to the New Jersey State Cancer Registry was conducted based on name, birth date, Social Security number, residential address, and sex using AutoMatch. Age- and sex-standardized incidence ratio (SIR) and exact 95% confidence intervals (CIs) were calculated using New Jersey (1979-2005) and US (1999-2009) cancer rates., Results: Among 3087 children (29,099 person-years; median follow-up: 9.8 years), 4 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 to 3.54) and national (SIR = 1.27; 95% CI: 0.26 to 3.70) reference rates., Conclusions: 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.

The purpose of this study was to estimate prenatal human immunodeficiency virus (HIV) screening rates prior to and on admission to labor and delivery (L&D) and to examine factors associated with HIV screening, including hospital policies, with a comparison of HIV and hepatitis B prenatal screening practices and hospital policies. In March 2006, a survey of hospitals (n = 190) and review of paired maternal and infant medical records (n = 4,762) were conducted in 50 US states, DC, and Puerto Rico. Data from the survey and medical record review were analyzed using SAS software v9.2 (SAS Institute, Cary, NC). HIV testing before delivery occurred among 3,438 women (73.9%); African American and Hispanic women were more likely to be tested than white women [aOR 2.22, 95% CI (1.6-3.1) and aOR 1.55, 95% CI (1.1-2.2), respectively]. Among women without previous HIV testing, 138 (16.6%) were tested after admission to labor and delivery. Policies to test women with undocumented HIV status in at delivery were present in 65 (36.3%) hospitals. HIV testing after admission to L&D was more likely in hospitals with policies to test women with undocumented HIV status [aOR 5.91, 95% CI (2.0-17.8)]. Overall, policies and screening practices for HIV were consistently less prevalent than those for hepatitis B. Many women are not being routinely screened for HIV before or at delivery. Women with unknown HIV status were more likely to be tested in L&D in hospitals with testing policies.

Objectives: We identified the level and type of program collaboration and service integration (PCSI) among HIV prevention programs in 59 CDC-funded health department jurisdictions., Methods: Annual progress reports (APRs) completed by all 59 health departments funded by CDC for HIV prevention activities were reviewed for collaborative and integrated activities reported by HIV programs for calendar year 2009. We identified associations between PCSI activities and funding, AIDS diagnosis rate, and organizational integration., Results: HIV programs collaborated with other health department programs through data-related activities, provider training, and providing funding for sexually transmitted disease (STD) activities in 24 (41%), 31 (53%), and 16 (27%) jurisdictions, respectively. Of the 59 jurisdictions, 57 (97%) reported integrated HIV and STD testing at the same venue, 39 (66%) reported integrated HIV and tuberculosis testing, and 26 (44%) reported integrated HIV and viral hepatitis testing. Forty-five (76%) jurisdictions reported providing integrated education/outreach activities for HIV and at least one other disease. Twenty-six (44%) jurisdictions reported integrated partner services among HIV and STD programs. Overall, the level of PCSI activities was not associated with HIV funding, AIDS diagnoses, or organizational integration., Conclusions: HIV programs in health departments collaborate primarily with STD programs. Key PCSI activities include integrated testing, integrated education/outreach, and training. Future assessments are needed to evaluate PCSI activities and to identify the level of collaboration and integration among prevention programs.

Background: Little is known about immune reconstitution inflammatory syndrome in children in the United States., Methods: LEGACY is a longitudinal cohort study of HIV-infected participants 0-24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the months pre- and postinitiation of the first highly active antiretroviral therapy (HAART) regimen which was followed by ≥1 log reduction in HIV viral load. We defined OI as immune reconstitution inflammatory syndrome if an OI incidence increased after HAART initiation. "Responders" were defined as experiencing ≥1 log decline in viral load within 6 months after HAART initiation., Results: Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were nonresponders and 86 experienced OI. Responders accounted for 98 of 124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders and 15.9 and 9.1 (P = 0.2), respectively, among nonresponders. Overall, OI incidences among responders and nonresponders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely than nonresponders to experience herpes simplex and herpes zoster before HAART initiation (all, P < 0.002)., Conclusions: The lack of immune reconstitution inflammatory syndrome in participants initiating HAART may be due to low overall OI rates. The unexpectedly higher OI prevalence comprised mainly of herpes simplex and zoster, before HAART initiation among responders, may have motivated them to better adhere to HAART.

Background: Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked., Objective: This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations., Methods: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies., Results: We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected., Conclusions: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.

Background: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown., Methods: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation., Results: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months., Conclusions: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

Background: Highly active antiretroviral therapy (HAART) has improved human immunodeficiency virus (HIV)-associated morbidity and mortality. The bimodal mortality distribution in HIV-infected children makes it important to evaluate temporal effects of HAART among a birth cohort with long-term, prospective follow-up., Methods: Perinatal AIDS Collaborative Transmission Study (PACTS)/PACTS-HIV Follow-up of Perinatally Exposed Children (HOPE) study was a Centers for Disease Control and Prevention-sponsored multicenter, prospective birth cohort study of HIV-exposed uninfected and infected infants from 1985 until 2004. Mortality was evaluated for the no/monotherapy, mono-/dual-therapy, and HAART eras, that is, 1 January 1986 through 31 December 1990, from 1 January 1991 through 31 December 1996, and 1 January 1997 through 31 December 2004., Results: Among 364 HIV-infected children, 56% were female and 69% black non-Hispanic. Of 98 deaths, 79 (81%) and 61 (62%) occurred in children ≤3 and ≤2 years old, respectively. The median age at death increased significantly across the eras (P < .0001). The average annual mortality rates were 18 (95% confidence interval [CI], 11.6-26.8), 6.9 (95% CI, 5.4-8.8), and 0.8 (95% CI, 0.4-1.5) events per 100 person-years for the no/monotherapy, mono-/dual-therapy and HAART eras, respectively. The corresponding 6-year survival rates for children born in these eras were 57%, 76%, and 91%, respectively (P < .0001). Among children who received HAART in the first 6 months of age, the probability of 6-year survival was 94%. Ten-year survival rates for HAART and non-HAART recipients were 94% and 45% (P < .05). HAART-associated reductions in mortality remained significant after adjustment for confounders (hazard ratio, 0.3; 95% CI, .08-.76). Opportunistic infections (OIs) caused 31.8%, 16.9%, and 9.1% of deaths across the respective eras (P = .051)., Conclusions: A significant decrease in annual mortality and a prolongation in survival were seen in this US perinatal cohort of HIV-infected children. Temporal decreases in OI-associated mortality resulted in relative proportional increases of non-OI-associated deaths.

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., (Published by Mosby, Inc.)

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.

Objective: To evaluate factors associated with receiving prenatal care among women who present in labor without human immunodeficiency virus documentation using the results of a previous study, Mother-Infant Rapid Intervention at Delivery., Design: Prospective, multicenter study., Setting: Eighteen hospitals in the United States., Participants: The present analysis is based on 667 peripartum women who completed a face-to-face interview after delivery. For purposes of this analysis, human immunodeficiency virus-infected and human immunodeficiency virus-uninfected women were considered together as the "study group.", Methods: The original study, Mother-Infant Rapid Intervention at Delivery, offered rapid human immunodeficiency virus testing to women in labor without human immunodeficiency virus testing documentation at 18 hospitals in the United States. This secondary study evaluated factors related to prenatal care, among participants who agreed to an interview after delivery., Results: Interviews were completed by 667 women. Of these, 26.8% reported no prenatal care before admission to labor and delivery. These women were more likely to have been born in the United States, have other children, used alcohol, and reported being unhappy. Those who reported receiving prenatal care were more likely to have had Medicaid, stronger social support, and reported good health., Conclusion: Women who are unlikely to receive prenatal care lack social support and are more likely to have additional social stressors. Medicaid may provide an important safety net to enhance access to care, because those with Medicaid were more likely to receive prenatal care. Further research is necessary to identify nontraditional models of care to enhance outreach to women at risk for no prenatal care.

Objective: To evaluate the acceptability and feasibility of rapid human immunodeficiency virus testing in obstetric outpatient settings., Study Design: The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study was a prospective, multicenter study. Women were offered rapid and conventional human immunodeficiency virus testing if they presented to outpatient settings late in pregnancy with undocumented human immunodeficiency virus status. We compared median times between conventional and rapid testing and between rapid point-of-care and rapid laboratory-based testing., Results: Among eligible women who were offered participation, 90% accepted testing. The median time from blood draw to result available was faster for rapid testing (25 minutes) than conventional testing (23 hours; P < .0001). For rapid tests, point-of-care testing was faster than laboratory-based testing (24 minutes vs 35 minutes; P < .0001). Almost 96% of rapid test results were available within 1 hour., Conclusion: Rapid human immunodeficiency virus testing is acceptable, feasible, and provides results far sooner than conventional testing in obstetric outpatient settings.

Background: In resource-poor regions of the world, HIV virologic testing is not available., Objective: We sought to evaluate the diagnostic usefulness of the CD4/CD8 T-cell ratio in predicting HIV infection in infants., Methods: Data from the 3- and 9-month visits for non-breast-fed infants born to HIV-infected mothers enrolled (1990-1994) in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study (mother-to-child transmission of HIV, 17%) were analyzed. Data from the 3-month visit for infants enrolled (1985-1996) in the Perinatal AIDS Collaborative Transmission Study (mother-to-child transmission of HIV, 18%) were used for validation., Results: At 3 months of age, data were available on 79 HIV-infected and 409 uninfected non-breast-fed infants in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study. The area under the curve (AUC) of the receiver operating characteristic curve at 3 months was higher for the CD4/CD8 ratio compared with the CD4(+) T-cell count (AUC, 0.83 and 0.75; P = .03). The mean CD4/CD8 ratio at the 3-month visit was 1.7 for HIV-infected infants and 3.0 for uninfected infants. A CD4/CD8 ratio of 2.4 at 3 months of age was almost 2.5 times more likely to occur in an HIV-infected infant compared with an uninfected infant (test sensitivity, 81%; posttest probability of HIV, 33%). Model performance in the Centers for Disease Control and Prevention Perinatal AIDS Collaborative Transmission Study validation test (224 HIV-infected and 1015 uninfected 3-month-old infants) was equally good (AUC, 0.78 for CD4/CD8 ratio)., Conclusion: The CD4/CD8 T-cell ratio is a more sensitive predictor of HIV infection in infants than the CD4(+) T-cell count., Clinical Implications: The CD4/CD8 T-cell ratio can be used with caution to predict HIV infection in children.

Cytomegalovirus (CMV) is the most important opportunistic infection in renal transplant recipients and is associated with an increased risk of rejection. Infection can be acquired post-operatively (from the transplanted organ) or from re-activation of latent disease. To identify risk factors for CMV disease in a pediatric population within 1 yr of renal transplant, and to generate hypotheses for the pathogenesis of CMV disease in this population, a review of all recipients from 1992 to 1998 in a children's hospital in Atlanta, Georgia, was undertaken. Medical records of 73 transplants performed on 72 patients were reviewed: nine (12.7%) of 72 individuals, after 73 procedures developed CMV disease. Median time to onset of CMV disease was 52 days post-transplant (range = 15-95 days). Receipts of mycophenolate mofetil (MMF), demographic factors, and use of cadaveric kidneys were not associated with a significantly elevated risk of CMV disease. Positive donor CMV serostatus was associated with CMV disease (uni-variate relative risk [RR] = 8.52, Fisher's Exact Test [FET] p = 0.010). Patients with transplants in October or November had a higher risk of developing CMV disease (four of 13; 30.8%) than patients transplanted in other months (five of 60, 8.3%); RR = 3.69; p = 0.047, FET). Most transplants of patients who did not develop CMV disease were performed in January through August (48/64; 75.0%); only 25.0% were performed in September through December. In contrast, six of nine (66.7%) transplants in patients who subsequently developed CMV disease were performed in September through December (p = 0.018, FET). Donor CMV-positive serostatus and transplant in October and November continued to be independently associated with an increased risk of CMV disease when controlled for other factors. The association of transplant in October and November with CMV disease in November-January may be related to an increased risk of seasonal community CMV exposure and primary CMV infection during the peak season for CMV circulation, with subsequent immune suppression promoting progression to disease. Alternatively, co-infection with seasonal pathogens after exposure from an infected donor during the period of immune suppression may promote progression from CMV infection to CMV disease. Further studies should be undertaken to explore these and other hypotheses, which may have implications for determination of a need for anti-viral prophylaxis.

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.

Objective: HIV infections in children are characterized by high viral load and, in some perinatally infected newborns, delayed appearance of viral markers. Both phenomena may be related to different levels of immune activation affecting viral replication. This study was designed to investigate the relationship between immune activation and viral replication in pediatric HIV infection, and the role of pre-existent immune activation in facilitating HIV transmission to the fetus/newborn., Design: Plasma levels of soluble L-selectin (s-LS), an immune activation marker, were determined in 100 infants with perinatally transmitted HIV infection, compared with 106 age-matched HIV-exposed uninfected controls. Included in the analysis were samples from 31 HIV-infected (10 PCR+ and 21 PCR-) and 35 uninfected newborns aged < 2 days., Methods: To determine s-LS levels, a solid phase ELISA was performed on plasma samples of patients and controls., Results: s-LS levels in uninfected children were higher than those in normal adults. HIV-infected patients had more rapidly increasing values in the first 6 months of life compared with uninfected infants. Plasma s-LS levels correlated with HIV viral loads (r, 0.50). Among newborns in the first 2 days of life, s-LS levels were lowest in those with negative PCR tests, compared with PCR-positive or uninfected infants., Conclusions: These results suggest that higher immune activation in children contributes to higher viral loads, and that the level of pre-existent immune activation may have a role in determining which infants have detectable virus in peripheral blood at birth.

Background and Methods: Enteritis necroticans (pigbel), an often fatal illness characterized by hemorrhagic, inflammatory, or ischemic necrosis of the jejunum, occurs in developing countries but is rare in developed countries, where its occurrence is confined to adults with chronic illnesses. The causative organism of enteritis necroticans is Clostridium perfringens type C, an anaerobic gram-positive bacillus. In December 1998, enteritis necroticans developed in a 12-year-old boy with poorly controlled diabetes mellitus after he consumed pig intestines (chitterlings). He presented with hematemesis, abdominal distention, and severe diabetic ketoacidosis with hypotension. At laparotomy, extensive jejunal necrosis required bowel resection, jejunostomy, and ileostomy. Samples were obtained for histopathological examination. Polymerase-chain-reaction (PCR) assay was performed on paraffin-embedded bowel tissue with primers specific for the cpa and cpb genes, which code for the alpha and beta toxins produced by C. perfringens., Results: Histologic examination of resected bowel tissue showed extensive mucosal necrosis, the formation of pseudomembrane, pneumatosis, and areas of epithelial regeneration that alternated with necrotic segments--findings consistent with a diagnosis of enteritis necroticans. Gram's staining showed large gram-positive bacilli whose features were consistent with those of clostridium species. Through PCR amplification, we detected products of the cpa and cpb genes, which indicated the presence of C. perfringens type C. Assay of ileal tissue obtained during surgery to restore the continuity of the patient's bowel was negative for C. perfringens., Conclusions: The preparation or consumption of chitterlings by diabetic patients and other chronically ill persons can result in potentially life-threatening infectious complications.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

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.

Objective: To estimate the perinatal HIV transmission rate and describe the natural history of infant HIV infection in a situation in which HIV status is known in more than 95% of delivering women., Design: A cohort of HIV-exposed infants born between 7 July 1987 and 30 June 1990, whose mothers were identified by routine voluntary universal HIV testing, were followed using clinical and laboratory measures., Setting: Grady Memorial Hospital, a major health-care site for individuals of lower socioeconomic status in Atlanta, Georgia, USA, with approximately 7000 deliveries per year., Patients: HIV-exposed infants (n = 165), 98% of whom were African American., Results: Annual maternal HIV seroprevalence increased from 0.58 to 0.86%. The annual proportion of HIV-positive women having a second delivery increased from 4.3 to 25%. Clinical outcome was known for 132 out of 165 infants (22 infected and 110 uninfected), the transmission rate was 17% (confidence interval, 11-24%). The rate declined to 11% by the third year of the study. Gestational growth, prematurity and mode of delivery were unrelated to infant outcome. There was a trend for intravenous drug use to be more common in mothers of infected infants (P = 0.08). After 35 months median follow-up of infected infants, eight out of 22 (36%) had an opportunistic infection (seven Pneumocystis carinii pneumonia); three out of 22 (14%) had lymphocytic interstitial pneumonia, and 10 out of 22 (45%) were asymptomatic or had only nonspecific symptoms. Cumulative mortality in infected infants was 9, 32 and 32% by 1, 2 and 3 years of age, respectively., Conclusion: In this cohort of HIV-exposed infants, perinatal HIV transmission was 17% overall. Factors affecting the transmission rate and possible future changes in the rate require further study.

A 10-year retrospective study of age-frequency, sites of infection, and pre-existing conditions in 297 children with Hemophilus influenzae (HI) disease seen at Grady Memorial Hospital from 1974 through 1984 is described. The majority of the patients were black (73%) and of lower socioeconomic status and were less than 2 years of age. Manifestations of HI disease were similar to those described in reports from other centers, with meningitis being the most common (56.7%). Epiglottitis was much less common in the present study than is generally reported. The death rate of all patients was 1.8 percent. The results of this study indicate that HI disease continues to be a significant risk in children less than 2 years of age.