Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.NICHD (NICHD)(Brazilian AIDS Prevention Trials International Network), NIAID/ NIHNational Institute of Allergy and Infectious Diseases (NIAID)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Institute of Mental Health (NIMH)Boehringer Ingelheim Pharmaceuticals Inc. (BIPI)GlaxoSmithKline, on behalf of ViiV HealthcareCepheid for the testing of CTNG in a prior HPTNUCLA Children's Discovery and Innovation Institute (CDI) through the Harry Winston Fellowship AwardUCLA AIDS InstituteUCLA Center for AIDS Research (CFAR) NIH/ NIAIDUCLA Pediatric AIDS Coalition, and WestatNIH/NICHDDavid Geffen UCLA Sch Med, Los Angeles, CA 90095 USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, RJ, BrazilUS Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USAElizabeth Glaser Pediat AIDS Fdn, Washington, DC USAHosp Geral Nova Iguacu, Nova Iguacu, RJ, BrazilHosp Fed Servidores Estado, Rio De Janeiro, RJ, BrazilUniv Witwatersrand, SAMRC & Perinatal HIV Res Unit, Johannesburg, South AfricaStellenbosch Univ, Tygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo, BrazilFdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, ArgentinaUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAUCLA, Fielding Sch Publ Hlth, Los Angeles, CA USAUCSD Sch Med, La Jolla, CA USAUC Davis Sch Med, Davis, CA USABoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilNICHD (NICHD): HHSN267200800001C, N01-HD-8-0001Brazilian AIDS Prevention Trials International Network: NIAID/ NIH [U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632, UM1AI068632, UM1AI068616, UM1AI106716NIMH: AI068632NG in a prior HPTN :040UCLA Center for AIDS Research (CFAR) NIH/ NIAID: AI02869, AI28697NIH/NICHD: HHSN275201300003CWeb of Scienc

Dental biofilm: ecological interactions in health and disease.

BACKGROUND: The oral microbiome is diverse and exists as multispecies microbial communities on oral surfaces in structurally and functionally organized biofilms. AIM: To describe the network of microbial interactions (both synergistic and antagonistic) occurring within these biofilms and assess their role in oral health and dental disease. METHODS: PubMed database was searched for studies on microbial ecological interactions in dental biofilms. The search results did not lend themselves to systematic review and have been summarized in a narrative review instead. RESULTS: Five hundred and forty-seven original research articles and 212 reviews were identified. The majority (86%) of research articles addressed bacterial-bacterial interactions, while inter-kingdom microbial interactions were the least studied. The interactions included physical and nutritional synergistic associations, antagonism, cell-to-cell communication and gene transfer. CONCLUSIONS: Oral microbial communities display emergent properties that cannot be inferred from studies of single species. Individual organisms grow in environments they would not tolerate in pure culture. The networks of multiple synergistic and antagonistic interactions generate microbial inter-dependencies and give biofilms a resilience to minor environmental perturbations, and this contributes to oral health. If key environmental pressures exceed thresholds associated with health, then the competitiveness among oral microorganisms is altered and dysbiosis can occur, increasing the risk of dental disease

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS)

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188–5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals

Exploratory Tools for National Children’s Study Data

The National Children’s Study Archive is an information, data, and sample repository for the National Children’s Study, designed to make data and samples freely available for scientific research, with an approved research request. The study, which was active from 2009 to 2014, collected data and samples from over 12,000 mothers, fathers, and children across the US at 40 study locations. These participants are currently represented by nearly 14,000 variables, over 200,000 biological samples, and over 4,000 environmental samples in the Archive. In order to facilitate meaningful evaluation and consumption of this wealth of data, the Archive has developed new exploratory tools. The Protocol Browser allows users to flow through the visit progression and visit instrumentation and identify available study datasets. The Participant Explorer allows users to investigate study participation by participant type (woman, child, father), demographics (e.g., education level, marital status), and data collection point. The Sample Explorer allows researchers to use demographics and study visit information to explore the available biological (blood, hair, nails, saliva, urine, vaginal swab, breast milk, cord blood, meconium, and placenta) and environmental (air, dust, water) primary and derivative samples that were collected from a subset of NCS families. Both the Participant and Sample Explorers provide researchers with the sample sizes available that fit the types of participants or samples of research of interest. The Variable Locator allows users to search the available NCS datasets for questions and variables of interest, returning specific data elements available. With these research tools, researchers targeting unique populations and topic areas can quickly establish if a particular topic area is represented in NCS data and samples. Once identified, researchers can use the Archive’s proposal submission and review process to begin using NCS resources to pursue their scientific objectives

Gender differences in lymphocyte populations, plasma HIV RNA levels, and disease progression in a cohort of children born to women infected with HIV

OBJECTIVE: We sought to document gender differences in lymphocyte subsets and plasma RNA levels in a pediatric cohort with presumed minimal hormonal differences (on the basis of age). METHODS: Blood samples from antiretroviral therapy-treated, HIV-infected children (n = 158) and HIV-uninfected children (n = 1801) who were enrolled in the Women and Infants Transmission Study were analyzed at specified study intervals with consensus protocols, and various parameters were compared. RESULTS: Antiretroviral therapy-treated, HIV-infected female children had, on average, 0.38 log10 copies per mL lower plasma RNA levels than did their male counterparts, but lymphocyte differences were not noted in this cohort. Despite their higher plasma RNA level, a greater proportion of male children survived through 8 years of age. There were no gender differences with respect to the age of diagnosis of HIV, time to antiretroviral therapy after diagnosis of HIV, or type of antiretroviral therapy. Lymphocyte differences were noted for uninfected children. CONCLUSIONS: Plasma RNA levels differed among antiretroviral therapy-treated, HIV-infected children according to gender, in a manner similar to that noted in previous pediatric and adult studies. Lymphocyte subsets varied according to gender in a cohort of HIV-exposed but uninfected children. Most importantly, overall mortality rates for this cohort differed according to gender

Consenting Postpartum Women for Use of Routinely Collected Biospecimens and/or Future Biospecimen Collection

The National Children’s Study (NCS) Harris County, Texas Study Center participated in the NCS Provider Based Sampling (PBS) substudy of the NCS Vanguard Phase pilot. As part of the hospital-based birth cohort component of the PBS substudy, we conducted a secondary data analysis to evaluate the proportion of postpartum women who consented to future biospecimen collection alone and to both future collection and use of residual birth biospecimens. In phase 1, 32 postpartum women at one hospital were asked to consent only to maternal future biospecimen collection. In phase 2, 40 other postpartum women from the same hospital were asked for an additional consent to use residual clinical biospecimens from the birth event that otherwise would be discarded, including cord blood and maternal blood and urine. Among 103 eligible women, a total of 72 participated. They were 28.3 ± 5.9 years old on average; 58 % were Hispanic; 63 % consented in English, and 37 % in Spanish; 39 % had some college education; 42 % were married; 60 % had an annual family income \u3c$30,000; and 51 % were employed. In phase 1, 59 % consented to future biospecimen collection, and in phase 2, 95 % consented to both future collection and use of at least one residual birth biospecimen, with a difference between phases of 36 % [95 % CI 17–54 %]. Demographic characteristics did not differ among those who did and did not consent. Postpartum women were significantly more likely to grant consent for use of future and residual hospital-obtained biospecimens than future biospecimen collection alone

Sinusitis in Children Infected with Human Immunodeficiency Virus: Clinical Characteristics, Risk Factors, and Prophylaxis

The clinical presentation, radiological and laboratory evaluation, treatment, and risk factors of sinusitis in a cohort of 376 human immunodeficiency virus (HIV)-infected children from a placebo-controlled clinical trial of intravenous immunoglobulin (IVIG) as prophylaxis for infections were examined. Ninety-five episodes of sinusitis were described in 60 patients; one-third of the patients had two or more episodes. Sinusitis episodes were commonly associated with nonspecific, chronic symptoms (67.4%, persistent nasal discharge; 54.7%, nocturnal or persistent cough), whereas symptoms more specific to acute sinusitis were less frequent (17.9%, headache or facial pain; 9.5%, periorbital swelling; 25.3%, temperature of ⩽102°F; 9%, total white blood cell count of ⩾15,000/ mm3). The sinuses primarily involved were the maxillary sinus (85.9%) and the ethmoidal sinus (42.3%); 36% of episodes involved two or more sinuses. Preceding respiratory infections did not appear to increase the risk of sinusitis, and CD4+ lymphocyte counts in children with and without sinusitis did not differ. Neither monthly IVIG prophylaxis nor three times weekly trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia decreased the risk of sinusitis. Sinusitis in HIV-infected children is most often subacute and recurrent. Evaluations of new modalities for prophylaxis for sinusitis are needed

Adolescent and young adult research across the HIV prevention and care continua: an international programme analysis and targeted review

Abstract Introduction Human immunodeficiency virus (HIV) continues to rise in young people among low‐ and middle‐income countries (LMIC). The US National Institutes of Health (NIH) supports the largest public investment in HIV research globally. Despite advancements in the last decade, adolescents and young adults (AYA) remain underrepresented in research to improve HIV prevention and care. We undertook a programme analysis of NIH grants and conducted a targeted review of linked publications on international AYA research across the HIV prevention and care continuum (HPCC) to inform new initiatives to address the needs of AYA in these settings. Methods NIH‐funded grants from 2012 to 2017, pertaining to AYA in LMIC, and evaluating areas of HIV prevention, care and/or treatment were identified. A systematic review of publications limited to funded grants was performed in two waves: 2012–2017 and 2018–2021. The review included a landscape assessment and an evaluation of NIH‐defined clinical trials, respectively. Data on outcomes across the HPCC were abstracted and analysed. Results Among grant applications, 14% were funded and linked to 103 publications for the analytic database, 76 and 27 from the first and second waves, respectively. Fifteen (15%) wave 1 and 27 (26%) wave 2 publications included an NIH‐defined clinical trial. Among these, 36 (86%) did not target a key population (men who have sex with men, drug users and sex workers) and 37 (88%) were exclusively focused on sub‐Saharan Africa. Thirty (71%) publications addressed at least one HPCC milestone. Specific focus was on milestones in HIV prevention, care or both, for 12 (29%), 13 (31%) and five (12%) of publications, respectively. However, few addressed access to and retention in HIV care (4 [14%]) and none included microbicides or treatment as prevention. More focus is needed in crucial early steps of the HIV care continuum and on biomedical HIV prevention interventions. Discussion and Conclusions Research gaps remain in this portfolio across the AYA HPCC. To address these, NIH launched an initiative entitled Prevention and Treatment through a Comprehensive Care Continuum for HIV‐affected Adolescents in Resource Constrained Settings (PATC3H) to generate needed scientific innovation for effective public health interventions for AYA affected by HIV in LMIC

Randomized Controlled Trial of Feeding a Concentrated Formula to Infants Born to Women Infected by Human Immunodeficiency Virus

OBJECTIVE:We tested the hypothesis that concentrated formula (CF) begun within the first 2 weeks of life increases growth in infants born to human immunodeficiency virus (HIV)–infected mothers. MATERIALS AND METHODS:HIV-exposed infants from the United States, the Bahamas, and Brazil were randomized in a double-blind, controlled trial to receive either a CF (87 kcal/100 mL [26 kcal/oz]) or a standard formula (SF; 67 kcal/100 mL [20 kcal/oz]) for 8 weeks. This article presents results for infants who were not determined to be HIV infected based on testing at 4 weeks. Primary outcomes were safety, tolerability, and growth in weight and length. RESULTS:Two thousand ninety-seven infants were enrolled, of whom 1998 were uninfected and had study formula dispensed. At weeks 4 and 8, uninfected infants receiving CF showed higher energy intake than those who were receiving SF (P < 0.001). By week 8, uninfected infants assigned to CF weighed more than infants receiving SF. There were no consistent differences in measures of tolerability, and rates of discontinuation or perceived formula intolerance were similar between treatment groups. CONCLUSIONS:A CF is well tolerated and results in increased weight gain compared with SF. Until the HIV status of an infant is reliably determined, early introduction of a CF in HIV-exposed children may have beneficial effects on growth. The role of early nutritional intervention remains to be determined for individuals living in countries with endemic malnutrition for whom formula feeding is a viable option