A multicenter study of diet quality on birth weight and gestational age in infants of HIV-infected women.

We determined factors associated with diet quality and assessed the relationship between diet quality, birth weight, and gestational age in a prospective national multicenter cohort study. We evaluated diet quality with the Healthy Eating Index (HEI, scale 0-100) in the third trimester of pregnancy with three 24-hr multiple-pass dietary recalls in 266 HIV+ women enrolled in the Pediatric HIV/AIDS Cohort Study. Covariates included demographics, food security, pre-pregnancy body mass index, HIV disease severity, substance use, and antiretroviral exposures. A two-stage multivariate process using classification and regression trees (CART) followed by multiple regression described HEI tendencies, controlled possible confounding effects, and examined the association of HEI with birth weight and gestational age. To assess the stability of the CART solution, both the HEI 2005 and 2010 were evaluated. The mean HEI scores were 56.1 and 47.5 for the 2005 and 2010 HEI, respectively. The first-stage CART analysis examined the relationship between HEI and covariates. Non-US born versus US-born mothers had higher HEI scores (15-point difference, R2  = 0.28). There was a secondary partition due to alcohol/cigarette/illicit drug usage (3.5-point difference, R2  = 0.03) among US-born women. For the second-stage CART adjusted multiple regression, birth weight z-score was positively related to HEI 2005 and 2010 (partial r's > 0.13, P's ≤ 0.0398), but not gestational age (r = 0.00). We conclude that diet quality among HIV+ women is associated with higher birth weight. Despite the influence of a large cultural effect and poor prenatal behaviors, interventions to improve diet in HIV+ women may help to increase birth weight.

Atazanavir exposure in utero and neurodevelopment in infants: a comparative safety study.

OBJECTIVE: To evaluate the safety of in-utero exposure to atazanavir and neurodevelopment in perinatally HIV-exposed but uninfected (PHEU) infants. DESIGN: Prospective cohort study of mother-PHEU infant pairs in the Surveillance Monitoring for ART Toxicities protocol of the Pediatric HIV/AIDS Cohort Study. METHODS: Pregnant women living with HIV who initiated an antiretroviral regimen during pregnancy were followed from the date of antiretroviral initiation. Women were classified according to whether the antiretroviral regimen contained atazanavir and the trimester of antiretroviral initiation. Neurodevelopment at 9-15 months was evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). We estimated mean differences for the five Bayley-III domains for atazanavir-containing regimens versus all other regimens. Models included baseline covariates and adjustment for failure to complete the Bayley-III using inverse probability weighting. RESULTS: PHEU infants were exposed in utero to atazanavir-containing (n = 167) and nonatazanavir-containing (n = 750) antiretroviral regimens. The adjusted mean differences (95% confidence interval) in Bayley-III domain scores for initiating an atazanavir-containing regimen in the first trimester were: cognitive, -1.5 (-6.2, 3.2); language, -3.3 (-7.6, 1.0); motor, -2.9 (-7.7, 1.9); social-emotional, 0.1 (-6.2, 6.4); and adaptive behavior, -0.1 (-4.3, 4.0). The mean differences for the second or third trimester were: cognitive, 0.4 (-3.2, 4.0); language, -3.4 (-6.2, -0.5); motor, 0.3 (-2.9, 3.4); social-emotional, -5.9 (-9.4, -2.3); and adaptive behavior, -2.5 (-5.9, 0.8). CONCLUSION: In-utero exposure to atazanavir-containing regimens compared with non-atazanavir-containing regimens may adversely affect language and social-emotional development in PHEU infants during the first year of life, but the absolute difference is small.

Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy.

BACKGROUND: Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. METHODS: We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. RESULTS: Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. CONCLUSIONS: Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01310023.

Meconium Tenofovir Concentrations and Growth and Bone Outcomes in Prenatally Tenofovir Exposed HIV-Uninfected Children.

BACKGROUND: Maternal tenofovir disoproxil fumarate (TDF) treatment among HIV-infected pregnant women results in fetal tenofovir (TFV) exposure. Fetal TFV toxicity was demonstrated in animals, but most clinical investigations have not observed toxicity in humans. METHODS: We evaluated HIV-exposed, uninfected infants in the Surveillance Monitoring for Antiretroviral Therapy Toxicities cohort of the Pediatric HIV/AIDS Cohort Study whose mothers were prescribed TDF for ≥ 8 third trimester weeks. Infant dual-energy X-ray absorptiometry scans were obtained at 0-4 weeks to measure whole body bone mineral content. Meconium TFV concentrations were quantified by liquid chromatography-tandem mass spectrometry. RESULTS: Fifty-eight TFV-exposed infants had meconium TFV quantified. Detectable concentrations were 11-48,100 ng/g; 3 infants had undetectable concentrations. Maternal TDF prescription duration ranged from 8 to 41 gestational weeks; infant gestational ages were 36-41 weeks. Meconium TFV concentrations were not correlated with TFV exposure duration or timing and did not vary by concomitant prescription of protease inhibitors. Increased meconium TFV concentrations were associated with greater gestational ages (ρ = 0.29, P = 0.03) and lower maternal plasma HIV RNA before delivery (ρ = -0.29, P = 0.04). Meconium TFV concentrations were not associated with infant weight, length (n = 58) or bone mineral content (n = 49). CONCLUSIONS: For the first time, we explored associations between meconium TFV concentrations and infant growth and bone measurements; we did not observe a meconium concentration-dependent relationship for these infant outcomes. These findings support other clinical research failing to show dose-response relationships for growth and bone outcomes among intrauterine TFV-exposed infants. High meconium TFV concentrations correlated with low maternal viral load, suggesting maternal TDF adherence significantly contributes to meconium TFV concentrations.

Dramatic decline in substance use by HIV-infected pregnant women in the United States from 1990 to 2012.

OBJECTIVE: We aimed to describe temporal changes in substance use among HIV-infected pregnant women in the United States from 1990 to 2012. DESIGN: Data came from two prospective cohort studies (Women and Infants Transmission Study and Surveillance Monitoring for Antiretroviral Therapy Toxicities Study). METHODS: Women were classified as using a substance during pregnancy if they self-reported use or had a positive biological sample. To account for correlation between repeated pregnancies by the same woman, generalized estimating equation models were used to test for temporal trends and evaluate predictors of substance use. RESULTS: Over the 23-year period, substance use among the 5451 HIV-infected pregnant women sharply declined; 82% of women reported substance use during pregnancy in 1990, compared with 23% in 2012. Use of each substance decreased significantly (P < 0.001 for each substance) in an approximately linear fashion, until reaching a plateau in 2006. Multivariable models showed substance use was inversely associated with receiving antiretroviral therapy. Among the subset of 824 women with multiple pregnancies under observation, women who used a substance in their previous pregnancy were at elevated risk of substance use during their next pregnancy (risk ratio, 5.71; 95% confidence interval, 4.63-7.05). CONCLUSION: A substantial decrease in substance use during pregnancy was observed between 1990 and 2012 in two large US cohorts of HIV-infected women. Substance use prevalence in these cohorts became similar to that of pregnant women in the general US population by the mid-2000s, suggesting that the observed decrease may be due to an epidemiological transition of the HIV epidemic among women in the United States.

Cardiac effects of in-utero exposure to antiretroviral therapy in HIV-uninfected children born to HIV-infected mothers.

OBJECTIVES: We evaluated the potential cardiac effects of in-utero exposures to antiretroviral drugs in HIV-exposed but uninfected (HEU) children. DESIGN AND METHODS: We compared echocardiographic parameters of left ventricular function (ejection fraction, fractional shortening, and stress-velocity index) and structure (left ventricular dimension, posterior wall/septal thickness, mass, thickness-to-dimension ratio, and wall stress) (expressed as Z-scores to account for age and body surface area) between HEU and HIV-unexposed cohorts from the Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring for ART Toxicities study. Within the HEU group, we investigated the associations between the echocardiographic Z-scores and in-utero exposures to maternal antiretroviral drugs. RESULTS: There were no significant differences in echocardiographic Z-scores between 417 HEU and 98 HIV-unexposed children aged 2-7 years. Restricting the analysis to HEU children, first-trimester exposures to combination antiretroviral therapy (a regimen including at least three antiretroviral drugs) and to certain specific antiretroviral drugs were associated with significantly lower stress-velocity Z-scores (mean decreases of 0.22-0.40 SDs). Exposure to combination antiretroviral therapy was also associated with lower left ventricular dimension Z-scores (mean decrease of 0.44 SD). First-trimester exposure to combination antiretroviral therapy was associated with higher mean left ventricular posterior wall thickness and lower mean left ventricular wall stress Z-scores. CONCLUSION: There was no evidence of significant cardiac toxicity of perinatal combination antiretroviral therapy exposure in HEU children. Subclinical differences in left ventricular structure and function with specific in-utero antiretroviral exposures indicate the need for a longitudinal cardiac study in HEU children to assess long-term cardiac risk and cardiac monitoring recommendations.

Cardiac status of children infected with human immunodeficiency virus who are receiving long-term combination antiretroviral therapy: results from the Adolescent Master Protocol of the Multicenter Pediatric HIV/AIDS Cohort Study.

IMPORTANCE: Prior to contemporary antiretroviral therapies (ARTs), children infected with human immunodeficiency virus (HIV) were more likely to have heart failure. This study suggests that highly active ART (HAART) does not appear to impair heart function. OBJECTIVE: To determine the cardiac effects of prolonged exposure to HAART on HIV-infected children. DESIGN: In the National Institutes of Health-funded Pediatric HIV/AIDS Cohort Study's Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiographic measures. SETTING: A total of 14 US pediatric HIV clinics. PARTICIPANTS: Perinatally HIV-infected children receiving HAART (n = 325), HIV-exposed but uninfected children (n = 189), and HIV-infected (mostly HAART-unexposed) historical pediatric controls from the National Institutes of Health-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study (n = 70). EXPOSURE Long-term HAART. MAIN OUTCOMES AND MEASURES: Echocardiographic measures of left ventricular (LV) function and structure. RESULTS: The 325 AMP HIV-infected children had lower viral loads, higher CD4 counts, and longer durations of ART than did the 70 HIV-infected children from the P2C2-HIV Study (all P < .001). The z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among HIV-infected children from the P2C2-HIV Study than among the AMP HIV-infected group or the 189 AMP HIV-exposed but uninfected controls (P < .05). For HIV-infected children, a lower nadir CD4 percentage and a higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening z scores; all P = .001) and an increased LV end-systolic dimension z score (all P < .03). In an interaction analysis by HIV-infected cohort, the HIV-infected children from the P2C2-HIV Study with a longer ART exposure or a lower nadir CD4 percentage had lower mean LV fractional shortening z scores, whereas the mean z scores were relatively constant among AMP HIV-infected children (P < .05 for all interactions). CONCLUSIONS AND RELEVANCE: Long-term HAART appears to be cardioprotective for HIV-infected children and adolescents.

Cardiac biomarkers in HIV-exposed uninfected children.

OBJECTIVES: To evaluate associations of cardiac biomarkers with in-utero antiretroviral drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. DESIGN AND METHODS: We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal antiretroviral drug exposures, maternal-child characteristics, and echocardiographic parameters. RESULTS: Among 338 HEU children (mean age 4.3 years), 51% had at least one elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP [adjusted odds ratio (aOR) 2.28, P=0.02]. Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR 3.56, P=0.01 and aOR 2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left-ventricular thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean left-ventricular end-diastolic (LVED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean left-ventricular contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). CONCLUSION: Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation.

Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants.

OBJECTIVE: To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. DESIGN: US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. METHODS: We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure. RESULTS: Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17 vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02). CONCLUSION: TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.

Point-of-care capillary blood lactate measurements in human immunodeficiency virus-uninfected children with in utero exposure to human immunodeficiency virus and antiretroviral medications.

OBJECTIVES: To estimate the prevalence of elevated point-of-care (POC) capillary blood lactate concentrations in human immunodeficiency virus (HIV)-exposed, uninfected children (HEU) and to determine if POC lactate varies with in utero antiretroviral (ARV) exposure. METHODS: The Surveillance Monitoring for Antiretroviral Therapy Toxicities protocol of the Pediatric HIV/AIDS Cohort Study enrolled 1934 children between 2007 and 2009, 0 to 12 years of age, born to HIV-infected mothers. POC lactate was measured annually on capillary blood using the Lactate Pro device. Associations of POC lactate with in utero ARV exposure and other characteristics were evaluated using logistic regression models, adjusting for maternal characteristics and other confounders. RESULTS: Of 1641 children with POC measurements (median age, 3.0 years), 3.4% had POC lactate >3 mmol/L. Median POC lactate level decreased with age (1.9 mmol/L, 1.7 mmol/L, and 1.6 mmol/L for children 0-<6 months [99% ≤6 weeks of life], 6-<24 months, and ≥24 months of age, respectively; P < 0.001). Prevalence of elevated POC lactate did not differ by in utero ARV exposure drug class, but was significantly higher in children exposed in utero to emtricitabine or efavirenz, cocaine or opiates, and those of white race. CONCLUSIONS: POC lactate testing is a useful rapid laboratory screening assay for HEU children with ARV exposure. ARV use during pregnancy has resulted in a dramatic decrease in mother-to-child transmission of HIV, and the risk of elevated lactate in HEU children is low. However, as new ARVs and more complex regimens are used during pregnancy by HIV-infected women, continued monitoring for infant toxicities is essential.

Cardiac effects of antiretroviral therapy in HIV-negative infants born to HIV-positive mothers: NHLBI CHAART-1 (National Heart, Lung, and Blood Institute Cardiovascular Status of HAART Therapy in HIV-Exposed Infants and Children cohort study).

OBJECTIVES: The aim of this study was to investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in human immunodeficiency virus (HIV)-negative children. BACKGROUND: ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals. METHODS: Using a prospective multisite cohort study design, echocardiograms taken between birth and 24 months were compared in 2 groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART-). RESULTS: Mean left ventricular (LV) mass z-scores were consistently lower in ART+ girls than in ART- girls: differences in mean z-scores were -0.46 at birth (p = 0.005), -1.02 at 6 months (p < 0.001), -0.74 at 12 months (p < 0.001), and -0.79 at 24 months (p < 0.001). Corresponding differences in z-scores for boys were smaller: 0.13 at 1 month (p = 0.42), -0.44 at 6 months (p = 0.01), -0.15 at 12 months (p = 0.37), and -0.21 at 24 months (p = 0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (p < 0.001). In ART+ infants, LV fractional shortening was higher than in ART- infants; girls showed a greater difference. CONCLUSIONS: Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function.

Association between HLA inheritance and asthma medication use in HIV positive children.

This study's purpose was to determine whether asthma medication use in HIV positive children is associated with human leukocyte antigen (HLA) alleles. We reviewed HLA and medication data collected during the Women and Infants Transmission Study for 124 HIV positive children and their mothers. Analysis revealed that HLA-A68 (P = 0.006) was independent and predictive for time to first asthma medication use. There was a preventive association of Cw6 (P = 0.008) with asthma time. Highly active antiretroviral therapy (HAART) was also associated with time to first asthma medication use (P = 0.05). HLA alleles may modulate risk of developing a need for asthma medications and seem to function independently of the actions of HAART therapy.

Antiretroviral exposure and lymphocyte mtDNA content among uninfected infants of HIV-1-infected women.

OBJECTIVE: Concern for potential adverse effects of antiretroviral (ARV) chemotherapy used to prevent mother-to-child HIV transmission has led the US Public Health Service to recommend long-term follow-up of ARV-exposed children. Nucleoside reverse transcriptase inhibitor ARV agents can inhibit DNA polymerase gamma, impairing mitochondrial DNA (mtDNA) synthesis and resulting in depletion or dysfunction. METHODS: We measured the mtDNA content of stored peripheral blood mononuclear cells (PBMCs) of 411 healthy children who were born to HIV-uninfected women and 213 uninfected infants who were born to HIV-infected women with or without in utero and neonatal ARV exposure. Cryopreserved PBMC mtDNA was quantified by using the Primagen Retina Mitox assay. RESULTS: Geometric mean PBMC mtDNA levels were lower at birth in infants who were born to HIV-infected women. Among HIV-exposed children, mtDNA levels were lowest in those who were not exposed to ARVs, higher in those with exposure to zidovudine alone, and higher still in those with combination nucleoside reverse transcriptase inhibitor exposure. A similar pattern was observed in the corresponding women. Levels of mtDNA increased during the first 5 years of life in all HIV-exposed children but achieved normal levels only in those with ARV exposure. CONCLUSIONS: Levels of mtDNA are lower than normal in HIV-exposed children. Contrary to expectation, PBMC mtDNA levels are significantly higher in ARV-exposed, HIV-uninfected infants and their infected mothers compared with ARV-unexposed infants and women. By 5 years, levels of PBMC mtDNA rise to normal concentrations in ARV-exposed children but remain depressed in ARV-unexposed children.

Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study.

BACKGROUND: Immunoreconstitution of HIV(+) patients after treatment with highly active antiretroviral therapy (HAART) appears to provoke inflammatory diseases. OBJECTIVE: We sought to determine whether HIV(+) children receiving HAART (HIV(+) HAART(+)) have a higher incidence of asthma than HIV(+) children not receiving HAART (HIV(+) HAART(-)). METHODS: Two thousand six hundred sixty-four children (193 HIV(+) and 2471 HIV(-) children) born to HIV(+) women were evaluated for the incidence and prevalence of asthma (ie, asthma medication use) and change of CD4(+) T-cell percentage with time. RESULTS: The HIV(+) HAART(+) children had higher CD4(+) T-cell percentages, lower CD8(+) T-cell percentages, and lower viral burdens than the HIV(+) HAART(-) children (P < or = .05 to P < or = .01). The cumulative incidence of asthma medication use in HIV(+) HAART(+) children at 13.5 years increased to 33.5% versus 11.5% in HIV(+) HAART(-) children (hazard ratio, 3.34; P = .01) and was equal to that in the HIV(-) children. In children born before the HAART era, the prevalence of asthma medication use for HIV(+) HAART(+) children at 11 years of age was 10.4% versus 3.8% for HIV(+) HAART(-) children (odds ratio, 3.38; P = .02) and was equal to that of the HIV(-) children. The rate of change of CD4(+) T cells around the time of first asthma medication for HIV(+) HAART(+) versus HIV(+) HAART(-) children was 0.81%/y versus -1.43%/y (P = .01). CONCLUSION: The increased incidence of asthma in HIV(+) HAART(+) children might be driven by immunoreconstitution of CD4(+) T cells.

Risk factors for in utero and intrapartum transmission of HIV.

OBJECTIVE: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000. METHODS: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age. RESULTS: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission. CONCLUSION: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.