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

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

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

Influence of NAT2 Genotype and Maturation on Isoniazid Exposure in Low-Birth-Weight and Preterm Infants With or Without Human Immunodeficiency Virus (HIV) Exposure.

BackgroundIsoniazid (INH) metabolism depends on the N-acetyl transferase 2 (NAT2) enzyme, whose maturation process remains unknown in low birth weight (LBW) and preterm infants. We aimed to assess INH exposure and safety in infants receiving oral tuberculosis prevention.MethodsThis population pharmacokinetics (PK) analysis used INH and N-acetyl-isoniazid (ACL) concentrations in infants (BW ≤ 4&nbsp;kg), including preterm, with follow-up for 6 months. PK parameters were described using nonlinear mixed effects modeling. Simulations were performed to assess INH exposure and optimal dosing regimens, using 2 targets: Cmax at 3-6&nbsp;mg/L and area under the curve (AUC) ≥ 10.52&nbsp;mg h/L.ResultsWe included 57 infants (79% preterm, 84% LBW) in the PK analysis, with a median (range) gestational age of 34 (28.7-39.4) weeks. At the time of sampling, postnatal age was 2.3 (0.2-7.3) months and weight (WT) was 3.7 (0.9-9.3) kg. NAT2 genotype was available in 43 (75.4%) patients (10 slow, 26 intermediate, and 7 fast metabolizers). Ninety percent of NAT2 maturation was attained by 4.4 post-natal months. WT, postmenstrual age, and NAT2 genotype significantly influenced INH exposure, with a 5-fold difference in AUC between slow and fast metabolizers for the same dose. INH appeared safe across the broad range of exposure for 61 infants included in the safety analysis.ConclusionsIn LBW/preterm infants, INH dosing needs frequent adjustment to account for growth and maturation. Pharmacogenetics-based dosing regimens is the most powerful approach to deliver safe and equalized exposures for all infants, because NAT2 genotype highly impacts INH pharmacokinetic variability