Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study.

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD following in utero exposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.

Demographics of Youth With Newly Diagnosed Acute/Recent HIV Infection in Adolescent Trials Network 147: Early Treatment of Acute HIV Infection.

PURPOSE: Gay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here. METHODS: Treatment-naïve, recently identified HIV + youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. RESULTS: Between July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). DISCUSSION: Early identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.

Can prenatal ultrasound predict adverse neonatal outcomes in SARS-CoV-2-affected pregnancies?

BACKGROUND: On the basis of available data, at least 1 ultrasound assessment of pregnancies recovering from SARS-CoV-2 infection is recommended. However, reports on prenatal imaging findings and potential associations with neonatal outcomes following SARS-CoV-2 infection in pregnancy have been inconclusive. OBJECTIVE: This study aimed to describe the sonographic characteristics of pregnancies after confirmed SARS-CoV-2 infection and assess the association of prenatal ultrasound findings with adverse neonatal outcomes. STUDY DESIGN: This was an observational prospective cohort study of pregnancies diagnosed with SARS-CoV-2 by reverse transcription polymerase chain reaction between March 2020 and May 2021. Prenatal ultrasound evaluation was performed at least once after diagnosis of infection, with the following parameters measured: standard fetal biometric measurements, umbilical and middle cerebral artery Dopplers, placental thickness, amniotic fluid volume, and anatomic survey for infection-associated findings. The primary outcome was the composite adverse neonatal outcome, defined as ≥1 of the following: preterm birth, neonatal intensive care unit admission, small for gestational age, respiratory distress, intrauterine fetal demise, neonatal demise, or other neonatal complications. Secondary outcomes were sonographic findings stratified by trimester of infection and severity of SARS-CoV-2 infection. Prenatal ultrasound findings were compared with neonatal outcomes, severity of infection, and trimester of infection. RESULTS: A total of 103 SARS-CoV-2-affected mother-infant pairs with prenatal ultrasound evaluation were identified; 3 cases were excluded because of known major fetal anomalies. Of the 100 included cases, neonatal outcomes were available in 92 pregnancies (97 infants); of these, 28 (29%) had the composite adverse neonatal outcome, and 23 (23%) had at least 1 abnormal prenatal ultrasound finding. The most common abnormalities seen on ultrasound were placentomegaly (11/23; 47.8%) and fetal growth restriction (8/23; 34.8%). The latter was associated with a higher rate of the composite adverse neonatal outcome (25% vs 1.5%; adjusted odds ratio, 22.67; 95% confidence interval, 2.63-194.91; P<.001), even when small for gestational age was removed from this composite outcome. The Cochran Mantel-Haenszel test controlling for possible fetal growth restriction confounders continued to show this association (relative risk, 3.7; 95% confidence interval, 2.6-5.9; P<.001). Median estimated fetal weight and birthweight were lower in patients with the composite adverse neonatal outcome (P<.001). Infection in the third trimester was associated with lower median percentile of estimated fetal weight (P=.019). An association between placentomegaly and third-trimester SARS-CoV-2 infection was noted (P=.045). CONCLUSION: In our study of SARS-CoV-2-affected maternal-infant pairs, rates of fetal growth restriction were comparable to those found in the general population. However, composite adverse neonatal outcome rates were high. Pregnancies with fetal growth restriction after SARS-CoV-2 infection were associated with an increased risk for the adverse neonatal outcome and may require close surveillance.

A necessary conversation to develop chatbots for HIV studies: qualitative findings from research staff, community advisory board members, and study participants.

Chatbots increase business productivity by handling customer conversations instead of human agents. Similar rationale applies to use chatbots in the healthcare sector, especially for health coaches who converse with clients. Chatbots are nascent in healthcare. Study findings have been mixed in terms of engagement and their impact on outcomes. Questions remain as to chatbot acceptability with coaches and other providers; studies have focused on clients.To clarify perceived benefits of chatbots in HIV interventions we conducted virtual focus groups with 13 research staff, eight community advisory board members, and seven young adults who were HIV intervention trial participants (clients). Our HIV healthcare context is important. Clients represent a promising age demographic for chatbot uptake. They are a marginalized population warranting consideration to avoid technology that limits healthcare access.Focus group participants expressed the value of chatbots for HIV research staff and clients. Staff discussed how chatbot functions, such as automated appointment scheduling and service referrals, could reduce workloads while clients discussed the after-hours convenience of these functions. Participants also emphasized that chatbots should provide relatable conversation, reliable functionality, and would not be appropriate for all clients. Our findings underscore the need to further examine appropriate chatbot functionality in HIV interventions.

Neuromotor repertoires in infants exposed to maternal COVID-19 during pregnancy: a cohort study.

OBJECTIVE: To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19. DESIGN: Longitudinal cohort study. SETTING: Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021. PARTICIPANTS: Infants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database. INTERVENTIONS: General movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database. MAIN OUTCOME MEASURES: Motor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months. RESULTS: 239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6-8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96). CONCLUSIONS: Compared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.

Longitudinal Evaluation of Antibody Persistence in Mother-Infant Dyads After Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Pregnancy.

BACKGROUND: There are limited data on how coronavirus disease 2019 (COVID-19) severity, timing of infection, and subsequent vaccination impact transplacental transfer and persistence of maternal and infant antibodies. METHODS: In a longitudinal cohort of pregnant women with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, maternal/infant sera were collected at enrollment, delivery/birth, and 6 months. Anti-SARS-CoV-2 spike immunoglobulin (Ig)G, IgM, and IgA were measured by enzyme-linked immunosorbent assay. RESULTS: Two-hundred fifty-six pregnant women and 135 infants were enrolled; 148 maternal and 122 neonatal specimens were collected at delivery/birth; 45 maternal and 48 infant specimens were collected at 6 months. Sixty-eight percent of women produced all anti-SARS-CoV-2 isotypes at delivery (IgG, IgM, IgA); 96% had at least 1 isotype. Symptomatic disease and vaccination before delivery were associated with higher maternal IgG at labor and delivery. Detectable IgG in infants dropped from 78% at birth to 52% at 6 months. In the multivariate analysis evaluating factors associated with detectable IgG in infants at delivery, significant predictors were 3rd trimester infection (odds ratio [OR] = 4.0), mild/moderate disease (OR = 4.8), severe/critical disease (OR = 6.3), and maternal vaccination before delivery (OR = 18.8). No factors were significant in the multivariate analysis at 6 months postpartum. CONCLUSIONS: Vaccination in pregnancy post-COVID-19 recovery is a strategy for boosting antibodies in mother-infant dyads.

Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth.

The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6-11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs.

Clinical and epidemiological characteristics of SARS-CoV-2 Infection in Los Angeles County youth during the first year of the pandemic.

OBJECTIVES: The aim of this study was to characterize SARS-CoV-2 infection patterns in Los Angeles (LA) County youth followed at our institution during the first pandemic year. DESIGN: A prospective cohort of patients aged < 25 years who tested positive for SARS-CoV-2 using reverse-transcriptase polymerase chain reaction (RT-PCR) assays between March 13, 2020, and March 31, 2021, was evaluated at a large LA County health network. Demographics, age distribution, and disease severity were analyzed. RESULTS: There were 28,088 youth aged < 25 years tested for SARS-CoV-2 using RT-PCR, with 1849 positive results identified (7%). Among the positive results, 475 of 11,922 (4%) were identified at the pandemic onset (March-September 2020) (Cohort 1) and 1374 of 16,166 (9%) between October 2020 and March 2021 (Cohort 2), P < 0.001. When disease severity was compared across cohorts, Cohort 2 had a greater proportion of asymptomatic and mild/moderate disease categories than Cohort 1 (98% vs 80%, respectively); conversely, Cohort 1 had a near-10-fold higher proportion of severe disease than Cohort 2 (17% vs 1.8%). Cohort 2 comprised younger patients with a mean age of 13.7 years vs 17.3 years in Cohort 1. Older age was associated with a higher percentage of infection, with 63% of all confirmed cases found in participants aged 19 to 25 years in Cohort 1, compared with 38% of confirmed cases in Cohort 2. Age increase was also associated with greater disease severity by linear regression modeling (P< 0.001). CONCLUSION: Coronavirus disease 2019 (COVID-19) disease severity in youth decreased over time in LA County during the first pandemic year, likely a reflection of changing demographics, with younger children infected. A higher infection rate in youth did not lead to higher disease severity over time.

Early Predictors of Poor Neurologic Outcomes in a Prospective Cohort of Infants With Antenatal Exposure to Zika Virus.

BACKGROUND: Identify early predictors of poor neurodevelopment in infants with antenatal Zika virus (ZIKV) exposure. METHODS: Analysis of a prospective cohort of infants with antenatal ZIKV exposure confirmed by maternal or infant RT-PCR or IgM during the epidemic in Rio de Janeiro, Brazil. Clinical findings before 3 months of age were associated with Bayley-III Scales of Infant and Toddler Development conducted after 6 months of age. RESULTS: ZIKV exposure was confirmed in 219 cases; 162 infants were normocephalic, 53 were microcephalic, 4 had no head circumference recorded because of perinatal death/LTFU. Seven of the 112 normocephalic infants developed secondary microcephaly between 3 weeks and 8 months of age. Among the normocephalic at birth cohort, the mean HCZ among normal, at risk, and developmentally delayed children was significantly different (ANOVA, P = 0.02). In particular, the mean HCZ of the developmentally delayed group was significantly lower than that of the normal group (Tukey's test, P = 0.014). HCZ was more strongly associated with lower expressive language scores (P = 0.04) than receptive language scores (P = 0.06). The rate of auditory abnormalities differed among the normal, at risk, and developmentally delayed groups (Chi-squared test, P = 0.016), which was driven by the significant difference between the normal and at risk groups (post hoc test, P = 0.011, risk ratio 3.94). Auditory abnormalities were associated with both expressive and receptive language delays (P = 0.02 and P = 0.02, respectively). CONCLUSIONS: Clear predictors of neurodevelopment in normocephalic ZIKV-exposed children have not been previously identified. Our findings demonstrate that smaller HCZ and auditory abnormalities in these infants correlate with poor neurodevelopment as toddlers. Language delay is the most prominent developmental concern among these children, who will require frequent auditory and speech evaluations throughout childhood.

Predictors of SARS-CoV-2 Infection in Youth at a Large, Urban Healthcare Center in California, March-September 2020.

Objective: To understand which social, epidemiologic, and clinical risk factors are associated with SARS-CoV-2 infection in youth accessing care in a large, urban academic institution. Methods: We conducted a prospective cohort study with case-control analyses in youth who received testing for SARS-CoV-2 at our academic institution in Los Angeles during the first wave of the COVID-19 pandemic (March-September 2020). Results: A total of 27,976 SARS-CoV-2 assays among 11,922 youth aged 0-24 years were performed, including 475 youth with positive SARS-CoV-2 results. Positivity rate was higher among older, African American, and Hispanic/Latinx youth. Cases were more likely to be from non-English-speaking households and have safety-net insurance. Zip codes with higher proportion of Hispanic/Latinx and residents living under the poverty line were associated with increased SARS-CoV-2 cases. Youth were more likely to have positive results if tested for exposure (OR 21.5, 95% CI 14.6-32.1) or recent travel (OR 1.5, 95% CI 1.0-2.3). Students were less likely to have positive results than essential worker youth (OR 0.5, 95% CI 0.3-0.8). Patterns of symptom presentation varied significantly by age group; number of symptoms correlated significantly with age in SARS-CoV-2 cases (r = 0.030, p < 0.001). SARS-CoV-2 viral load did not vary by symptom severity, but asymptomatic youth had lower median viral load than those with symptoms (21.5 vs. 26.7, p = 0.009). Conclusions: Socioeconomic factors are important drivers of SARS-CoV-2 infection in youth. Presence of symptoms, exposure, and travel can be used to drive testing in older youth. Policies for school reopening and infection prevention should be tailored differently for elementary schools and universities.

The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2.

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1ß/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

The Effect of Partnership Presence and Support on HIV Viral Suppression Among Serodiscordant Partnered and Single Heterosexual HIV-Positive Individuals in Brazil.

HIV-negative individuals in serodiscordant partnerships experience reduced risk of HIV acquisition when their partners adhere to ART and achieve undetectable viral loads. Partnership support may encourage ART adherence, reducing viral load and the risk of HIV transmission. This study aims to determine whether HIV viral suppression is associated with partnership status and partnership support among 201 HIV positive (HIV+ individuals in serodiscordant partnerships and 100 HIV+ unpartnered individuals receiving care at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil between 2014 and 2016. Clinical data and patient-reported questionnaire data were assessed, and propensity scores were used to control for confounding variables in adjusted logistic regression models. Viral suppression did not significantly differ between HIV+ partnered (78.5% virally suppressed) and unpartnered (76.0% virally suppressed) individuals. Among individuals in partnerships, viral suppression was significantly associated with having a partner who attended monthly clinic visits (AOR 2.99; 95% CI 1.00-8.93). Instrumental social support-attending monthly visits-may improve the odds of viral suppression among HIV+ individuals in serodiscordant relationships.

Zika Virus Infection Leads to Variable Defects in Multiple Neurological Functions and Behaviors in Mice and Children.

Zika virus (ZIKV) has evolved into a global health threat because of its causal link to congenital Zika syndrome. ZIKV infection of pregnant women may cause a spectrum of abnormalities in children. In the studies in Brazil, a large cohort of children with perinatal exposure to ZIKV is followed, and a spectrum of neurodevelopmental abnormalities is identified. In parallel, it is demonstrated that infection of the mouse neonatal brain by a contemporary ZIKV strain instead of an Asian ancestral strain can cause microcephaly and various abnormal neurological functions. These include defects in social interaction and depression, impaired learning and memory, in addition to severe motor defects, which are present in adult mice as well as in the prospective cohort of children. Importantly, although mouse brains infected later after birth do not have apparent abnormal brain structure, those mice still show significant impairments of visual cortical functions, circuit organization, and experience-dependent plasticity. Thus, the study suggests that special attention should be paid to all children born to ZIKV infected mothers for screening of abnormal behaviors and sensory function during childhood.

Association Between Antenatal Exposure to Zika Virus and Anatomical and Neurodevelopmental Abnormalities in Children.

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.

Zika virus vertical transmission in children with confirmed antenatal exposure.

We report Zika virus (ZIKV) vertical transmission in 130 infants born to PCR+ mothers at the time of the Rio de Janeiro epidemic of 2015-2016. Serum and urine collected from birth through the first year of life were tested by quantitative reverse transcriptase polymerase chain reaction (PCR) and/or IgM Zika MAC-ELISA. Four hundred and seven specimens are evaluated; 161 sera tested by PCR and IgM assays, 85 urines by PCR. Sixty-five percent of children (N = 84) are positive in at least one assay. Of 94 children tested within 3 months of age, 70% are positive. Positivity declines to 33% after 3 months. Five children are PCR+ beyond 200 days of life. Concordance between IgM and PCR results is 52%, sensitivity 65%, specificity 40% (positive PCR results as gold standard). IgM and serum PCR are 61% concordant; serum and urine PCR 55%. Most children (65%) are clinically normal. Equal numbers of children with abnormal findings (29 of 45, 64%) and normal findings (55 of 85, 65%) have positive results, p = 0.98. Earlier maternal trimester of infection is associated with positive results (p = 0.04) but not clinical disease (p = 0.98). ZIKV vertical transmission is frequent but laboratory confirmed infection is not necessarily associated with infant abnormalities.

HIV-1 heterosexual transmission and association with sexually transmitted infections in the era of treatment as prevention.

OBJECTIVES: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. METHODS: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3-16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. RESULTS: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p=0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55-61.2; p=0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. CONCLUSIONS: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting.

Delayed childhood neurodevelopment and neurosensory alterations in the second year of life in a prospective cohort of ZIKV-exposed children.

We report neurodevelopmental outcomes in 216 infants followed since the time of PCR-confirmed maternal Zika virus (ZIKV) infection in pregnancy during the Rio de Janeiro epidemic of 2015-2016 (refs. 1,2). Neurodevelopment was assessed by Bayley Scales of Infant and Toddler Development, third edition (Bayley-III; cognitive, language and motor domains) in 146 children and through neurodevelopment questionnaires/neurological examinations in 70 remaining children. Complete eye exams (n = 137) and hearing assessments (n = 114) were also performed. Below-average neurodevelopment and/or abnormal eye or hearing assessments were noted in 31.5% of children between 7 and 32 months of age. Among children assessed by Bayley-III, 12% scored below -2 s.d. (score <70; a score of 100 ± 2 s.d. is the range) in at least one domain; and 28% scored between -1 and -2 s.d. in any domain (scores <85-70). Language function was most affected, with 35% of 146 children below average. Improved neurodevelopmental outcomes were noted in female children, term babies, children with normal eye exams and maternal infection later in pregnancy (P = 0.01). We noted resolution of microcephaly with normal neurodevelopment in two of eight children, development of secondary microcephaly in two other children and autism spectrum disorder in three previously healthy children in the second year of life.

Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil.

BACKGROUND: An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. METHODS: A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. RESULTS: The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2-4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. CONCLUSIONS: ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression.