scholarly journals 364. Association of Maternal ARV Use with Microcephaly in HIV-Exposed Uninfected Children

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S191-S191
Author(s):  
Paige L Williams ◽  
Cenk Yildirim ◽  
Ellen G Chadwick ◽  
Russell B Van Dyke ◽  
Renee Smith ◽  
...  
Keyword(s):  
Hiv Transmission ◽  
In Utero ◽  
Sensitivity Analyses ◽  
Relative Risks ◽  
Perinatal Hiv ◽  
Increased Risk ◽  
Hiv Exposed ◽  
Ongoing Surveillance ◽  
Combination Regimens ◽  
Exposed Uninfected

Abstract Background Perinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among HIV-exposed uninfected (HEU) children, such as microcephaly, warrant ongoing surveillance. Methods We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network at 22 US sites. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measured at 6–36 months of age (z-score <−2) and using Nellhaus standards (<2nd percentile) after age 3 (“SMARTT” criteria), or using Nellhaus standards across all ages. Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero ARV exposure and microcephaly status, adjusted for potential confounders. Sensitivity analyses were conducted. Neurodevelopmental functioning was compared between HEU children with vs. without microcephaly. Results Among 3055 SMARTT participants enrolled as of April 2017 with a HC measurement over 5.1 years median follow-up (IQR = 3.0, 7.2), 159 (5.2%, 95% CI: 4.4–6.1%) had microcephaly identified by Nellhaus criteria and 70 (2.3%, 95% CI: 1.8–2.9%) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4.7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (aRR=2.02, 95% CI: 1.16, 3.51) and SMARTT criteria (adjusted RR = 2.56, 95% CI: 1.22, 5.37). These associations were more pronounced among children exposed to combination regimens of efavirenz which included zidovudine+lamivudine than those including tenofovir+emtricitabine (Figure 1). Associations of microcephaly with efavirenz persisted in several sensitivity analyses (Figure 2). Protective associations were observed for darunavir exposure (aRR = 0.50; 95% CI: 0.24, 1.00). HEU children with microcephaly had lower mean scores on neurodevelopmental assessments at ages 1 and 5 years and higher prevalence of impairment than those without microcephaly. Conclusion Efavirenz exposure during pregnancy was associated with a higher risk of microcephaly in infancy and childhood. These findings may support identification of alternatives to efavirenz as part of first-line ARV therapy. Disclosures All authors: No reported disclosures.

scholarly journals LB5. Safety of In Utero Antiretroviral (ARV) Exposure: Neurologic Outcomes in HIV-Exposed, Uninfected Children

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S761-S761 ◽  
Author(s):  
Claudia S Crowell ◽  
Paige Williams ◽  
Cenk Yildirim ◽  
Russell Van Dyke ◽  
Renee Smith ◽  
...  
Keyword(s):  
Cohort Study ◽  
In Utero ◽  
Pediatric Hiv ◽  
Sensitivity Analyses ◽  
Neurologic Outcomes ◽  
Case Status ◽  
Hiv Exposed ◽  
Stock Dividends ◽  
Exposed Uninfected

Abstract Background Antiretroviral therapy for pregnant women with HIV has dramatically decreased perinatal transmission of HIV, but concerns remain regarding adverse neurologic outcomes from possible mitochondrial dysfunction or other mechanisms in children exposed in utero to antiretroviral (ARV) medications. Method We evaluated HIV-exposed uninfected (HEU) children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a longitudinal observational cohort study conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network. The primary outcome of interest was a “neurologic case” (microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, other neurologic conditions) as determined by clinical review blinded to ARV exposure. Log-binomial regression analysis was used to obtain adjusted relative risks (aRRs) for associations between in utero ARV exposure and neurologic case status, accounting for potential confounders including Hispanic ethnicity, tobacco use during pregnancy, and birth cohort (2011–2014 and 2015–2017 vs. &lt;2011). To account for variable person-time follow-up within the cohort, Poisson regression models for adjusted incidence rate ratios (aIRRs) were also fitted. Result Among 3,747 eligible HEU children enrolled in SMARTT (52% male, 68% Black and 31% Hispanic), 237 were diagnosed with neurologic conditions, yielding an event rate of 6.3% (95% CI: 5.6%, 7.2%). Tobacco and alcohol use during pregnancy were common (17% and 8%, respectively). The majority of children had in utero ARV exposure (87%); 60% to PI-based regimens, 16% to NNRTI-based regimens and 7% to PI + NNRTI-based regimens. In adjusted models, there was a trend towards an association between efavirenz exposure (EFV) and neurologic case status (aRR: 1.60, 95% CI: 0.99, 2.58). This association was statistically significant in sensitivity analyses restricted to children enrolled prior to or shortly after birth (aRR: 1.80, 95% CI: 1.06, 3.05), excluding children with confirmed congenital anomalies (aRR: 1.66, 95% CI: 1.02, 2.64), and accounting for person-time follow-up (aIRR: 1.55, 95% CI: 1.00, 2.76). Conclusion EFV exposure during pregnancy was associated with a higher risk of neurologic abnormalities in infancy and childhood. Disclosures R. Van Dyke, Giliad Sciences: Grant Investigator, Research grant. E. G. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends.

Neurodevelopmental outcomes and in-utero antiretroviral exposure in HIV-exposed uninfected children

AIDS ◽  
2018 ◽  
Vol 32 (17) ◽  
pp. 2583-2592 ◽  
Author(s):  
Micah Piske ◽  
Matthew A. Budd ◽  
Annie Q. Qiu ◽  
Evelyn J. Maan ◽  
Laura J. Sauvé ◽  
...  
Keyword(s):  
In Utero ◽  
Neurodevelopmental Outcomes ◽  
Hiv Exposed ◽  
Exposed Uninfected

scholarly journals In Utero ART Exposure and Birth and Early Growth Outcomes Among HIV-Exposed Uninfected Infants Attending Immunization Services: Results From National PMTCT Surveillance, South Africa

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Vundli Ramokolo ◽  
Ameena E Goga ◽  
Carl Lombard ◽  
Tanya Doherty ◽  
Debra J Jackson ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Odds Ratio ◽  
In Utero ◽  
Early Growth ◽  
Adverse Birth Outcomes ◽  
Growth Outcomes ◽  
Immunization Services ◽  
Future Policy ◽  
Hiv Exposed ◽  
Exposed Uninfected

Abstract Background Despite the recognized benefit of antiretroviral therapy (ART) for preventing and treating HIV, some studies have reported adverse birth outcomes with in utero ART exposure. We evaluated the effect of infant in utero HIV and ART exposure on preterm delivery (PTD), low birth weight (LBW), small for gestational age (SGA), and underweight for age (UFA) at 6 weeks. Methods We surveyed 6179 HIV-unexposed-uninfected (HUU) and 2599 HIV-exposed-uninfected (HEU) infants. HEU infants were stratified into 3 groups: ART, Zidovudine alone, and no antiretrovirals (None). The ART group was further stratified to explore pre- or postconception exposure. Multivariable logistic regression evaluated effects of HIV and ARV exposure on the outcomes. Results We found higher odds of PTD, LBW, SGA, and UFA in HEU than HUU infants. HEU in the None group (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2–3.0) or those whose mothers initiated ART preconception (AOR, 1.7; 95% CI, 1.1–2.5) had almost twice the odds of PTD than infants whose mothers started ART postconception, but no increased odds for other outcomes. Conclusions There was an association between preconception ART and PTD. As ART access increases, pregnancy registers or similar surveillance should be in place to monitor outcomes to inform future policy.

Predictors of attempted suicide among youth living with perinatal HIV infection and perinatal HIV exposed uninfected counterparts

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Philip Kreniske ◽  
Claude Ann Mellins ◽  
Curtis Dolezal ◽  
Corey Morrison ◽  
Eileen Shea ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Attempted Suicide ◽  
Perinatal Hiv ◽  
Hiv Exposed ◽  
Exposed Uninfected

scholarly journals Effect of in utero exposure to HIV and antiretroviral drugs on growth in HIV-exposed uninfected children: a systematic review and meta-analysis protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e023937 ◽  
Author(s):  
Gabriel L Ekali ◽  
Julie Jesson ◽  
Pascal B Enok ◽  
Valériane Leroy
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
In Utero ◽  
Antiretroviral Drugs ◽  
Morbidity And Mortality ◽  
Cochrane Library ◽  
Growth Disorders ◽  
Growth Impairment ◽  
Hiv Exposed ◽  
Exposed Uninfected

IntroductionHIV-exposed uninfected (HEU) children have higher morbidity and mortality compared with HIV unexposed uninfected children. Despite the fact that malnutrition contributes to about half of all infant deaths below 5 years of age in low-income and middle-income countries and that growth impairment has been reported in the HEU population, the spectrum of growth disorders associated with HIV and antiretroviral therapy (ART) exposure during the in utero and perinatal periods is yet to comprehensively summarised among the global HEU population. This protocol for a systematic review and meta-analysis aims to critically synthesise data concerning the prevalence of underweight, stunting and wasting at different ages in the global HEU population.Methods and analysisMedline, EMBASE, Cochrane Library, TOXLINE, WHO Global Index Medicus and the Web of Science will be searched for relevant articles published between 1 January 1989 and 1 December 2017 without language restriction. In addition, conference abstracts and reference lists of eligible papers and relevant review articles will be screened. Authors will screen and select studies, extract data, assess the risk of bias as well as studies individually for heterogeneity. Study-specific estimates will be pooled through a random-effects meta-analysis model for studies that are clinically homogeneous while funnel plots and Egger’s test will be used to detect publication bias. Results will be presented by ART availability period, country income levels and mode of breastfeeding.Ethics and disseminationEthical approval will not be required for this study because it will be based on published data. The final report of this study will be published in a peer-reviewed journal and presented at scientific conferences. This review will summarise the evidence and quantify the problem of growth impairment in HEU infants and so shed more light on our understanding of the higher morbidity and mortality in this growing population.PROSPERO registration numberCRD42018091762.

scholarly journals Blood pressure, hypertension and the risk of sudden cardiac death: a systematic review and meta-analysis of cohort studies

2019 ◽  
Vol 35 (5) ◽  
pp. 443-454 ◽  
Author(s):  
Han Pan ◽  
Makoto Hibino ◽  
Elsa Kobeissi ◽  
Dagfinn Aune
Keyword(s):  
Blood Pressure ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Dose Response Relationship ◽  
Future Studies ◽  
Relative Risks ◽  
Increased Risk ◽  
Hypertension Diagnosis

AbstractCardiovascular disease is the leading cause of death worldwide, while sudden cardiac death (SCD) accounts for over 60% of all cardiovascular deaths. Elevated blood pressure and hypertension have been associated with increased risk of SCD, but the findings have not been consistent. To clarify whether blood pressure or hypertension is associated with increased risk of SCD and to quantify the size and the shape of any association observed. PubMed and Embase databases were searched for published prospective studies on blood pressure or hypertension and SCD up to 30 April 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The meta-analysis included 2939 SCDs among 418,235 participants from 18 studies. The summary RRs were 2.10 (95% CI 1.71–2.58, I2 = 56.7%, pheterogeneity = 0.018, n = 10) for prevalent hypertension, 1.28 (95% CI 1.19–1.38, I2 = 45.5%, pheterogeneity = 0.07, n = 10) per 20 mmHg increment in systolic blood pressure (SBP) and 1.09 (95% CI 0.83–1.44, I2 = 83.4%, pheterogeneity = 0.002, n = 3) per 10 mmHg increment in diastolic blood pressure (DBP). A nonlinear relationship was suggested between SBP and SCD. The results persisted in most subgroup and sensitivity analyses. There was no evidence of publication bias. This meta-analysis found an increased risk of SCD with hypertension diagnosis and increasing SBP. Future studies should clarify the association for DBP and the shape of the dose–response relationship between blood pressure and SCD.

scholarly journals Association of Selected Phenotypic Markers of Lymphocyte Activation and Differentiation with Perinatal Human Immunodeficiency Virus Transmission and Infant Infection

2005 ◽  
Vol 12 (5) ◽  
pp. 622-631 ◽  
Author(s):  
John S. Lambert ◽  
Jack Moye ◽  
Susan F. Plaeger ◽  
E. Richard Stiehm ◽  
James Bethel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Lymphocyte Activation ◽  
Phenotypic Markers ◽  
Perinatal Hiv ◽  
Hla Dr ◽  
Increased Risk ◽  
Immunodeficiency Virus

ABSTRACT This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells. Most notably, levels of total CD8+ T cells and CD8+ CD38+ cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naïve CD4+ T cells were significantly higher in uninfected than infected infants. Total CD8+ cells, as well as CD8+cells positive for HLA-DR+, CD45 RA+ HLA-DR+, and CD28+ HLA-DR+ were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.

scholarly journals Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of highly active anti-retroviral therapy

2021 ◽  
Author(s):  
Louise Afran ◽  
Kondwani C Jambo ◽  
Wilfred Nedi ◽  
David J.C Miles ◽  
Anmol Kiran ◽  
...  
Keyword(s):  
B Cell ◽  
Sub Saharan Africa ◽  
Haemophilus Influenzae Type ◽  
Cell Phenotype ◽  
Bacterial Disease ◽  
Enzymatic Function ◽  
Increased Risk ◽  
Hiv Exposure ◽  
Hiv Exposed ◽  
Exposed Uninfected

HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in Sub Saharan Africa and are highly particularly susceptible to disease caused by encapsulated bacteria in the first year of life. The mechanism of this increased risk is still poorly understood and we therefore, investigated if HIV exposure dysregulates HEU infant immunity and if this is amplified by human herpes infection (HHV). Here, we compared monocyte enzymatic function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HUU infants. We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HUU infants. There was no difference in the prevalence of HHV infection between HEU and HUU infants. Our findings suggest that even in the era of ART-mediated viral suppression, HIV exposure dysregulates monocyte and B cell function during a vulnerable period of immune maturation in infancy. This may contribute to the high rates of bacterial disease and pneumonia in HEU infants.

Missed Opportunities for Perinatal HIV Prevention Among HIV-Exposed Infants Born 1996–2000, Pediatric Spectrum of HIV Disease Cohort

PEDIATRICS ◽  
2003 ◽  
Vol 111 (Supplement_1) ◽  
pp. 1186-1191 ◽  
Author(s):  
Vicki Peters ◽  
Kai-Lih Liu ◽  
Kenneth Dominguez ◽  
Toni Frederick ◽  
Sharon Melville ◽  
...  
Keyword(s):  
Drug Use ◽  
Hiv Prevention ◽  
Prenatal Care ◽  
Hiv Testing ◽  
Hiv Transmission ◽  
Illicit Drug ◽  
Missed Opportunities ◽  
Perinatal Hiv ◽  
Hiv Exposed ◽  
Perinatal Hiv Prevention

Objective. Despite dramatic reductions in perinatal human immunodeficiency virus (HIV) transmission in the United States, obstacles to perinatal HIV prevention that include lack of prenatal care; failure to test pregnant women for HIV before delivery; and lack of prenatal, intrapartum, or neonatal antiretroviral (ARV) use remain. The objective of this study was to describe trends in perinatal HIV prevention methods, perinatal transmission rates, and the contribution of missed opportunities for perinatal HIV prevention to perinatal HIV infection. Methods. We analyzed data obtained from infant medical records on 4755 HIV-exposed singleton deliveries in 1996–2000, from 6 US sites that participate in the Centers for Disease Control and Prevention’s Pediatric Spectrum of HIV Disease Project. HIV-exposed deliveries refer to deliveries in which the mother was known to have HIV infection during the pregnancy. Results. Of the 4287 women with data on prenatal care, 92% had prenatal care. From 1996 to 2000, among the 3925 women with prenatal care, 92% had an HIV test before delivery; the use of prenatal zidovudine (ZDV) alone decreased from 71% to 9%, and the use of prenatal ZDV with other ARVs increased from 6% to 70%. Complete data on maternal and neonatal ARVs were available for 3284 deliveries. Perinatal HIV transmission was 3% in 1651 deliveries with prenatal ZDV in combination with other ARVs, intrapartum ZDV, and neonatal ZDV; 6% in 1111 deliveries with prenatal, intrapartum, and neonatal ZDV alone; 8% in 152 deliveries with intrapartum and neonatal ZDV alone; 14% of 73 deliveries with neonatal ZDV only started within 24 hours of birth; and 20% in 297 deliveries with no prenatal, intrapartum, and neonatal ARVs. Complete data on prenatal events were available in 328 HIV-infected and 3258 HIV-uninfected infants. A total of 56% of mothers of HIV-infected infants had missed opportunities for perinatal HIV prevention versus 16% of mothers of HIV-uninfected infants. Forty-four percent of the infected infants were born to mothers who had prenatal care, a prenatal HIV diagnosis, and documented prenatal ARV therapy. Seventeen percent of women with reported illicit drug use had no prenatal care versus 3% of women with no reported drug use. In a multivariate analysis, maternal illicit drug use was significantly associated with lack of prenatal care. In a multivariate analysis, year of infant birth and the combination of lack of maternal HIV testing before delivery and lack of prenatal antiretroviral therapies were significantly associated with perinatal HIV transmission. Conclusions. Missed opportunities for perinatal HIV prevention contributed to more than half of the cases of HIV-infected infants. Prenatal care and HIV testing before delivery are major opportunities for perinatal HIV prevention. Illicit drug use was highly associated with lack of prenatal care, and lack of HIV testing before delivery was highly associated with perinatal HIV transmission.

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