Vertical HIV Infection Research Articles

Pediatric perspective: the microbiome in vertical HIV-infection: unravelling gaps, challenges, and therapeutic potential.

The intricate interplay between HIV and the host microbiota has emerged as a significant area of investigation with therapeutic potential. Despite numerous studies on this complex interaction in adults, vertically acquired infections, which have distinct immunological and virological characteristics, remain relatively understudied. Disturbances, including prolonged exposure to HIV and antiretroviral therapy, significantly impact the gut microbiome, though isolating these effects from other influencing factors is challenging. Children and adolescents living with HIV exhibit reduced microbiome diversity and potential imbalances between beneficial and pathogenic taxa. However, most available data focus on microbiome composition rather than function. The observed variations in specific microbial phyla are intriguing, but their health effects are unknown. Although modulating the microbiota may be theoretically easier during childhood, few interventional trials have included children. Therapeutic interventions aimed at modulating the gut microbiome in children with HIV have shown limited impact, and their ability to induce long-term microbiome changes remains uncertain. A more functional, longitudinal approach, along with an ecological perspective, is needed to understand the complex interplay between the microbiome and the host. This will help clarify the relevance of microbiota alterations and their potential implications for clinical outcomes, such as inflammation and immune reconstitution in pediatric HIV.

HIV Drug Resistance Mutations and Subtype Profiles among Pregnant Women of Ho Chi Minh City, South Vietnam.

According to the latest data released by UNAIDS, the global number of people living with HIV (PLHIV) in 2021 was 38.4 million, with 1.5 million new HIV infections. In different countries, a significant proportion of these cases occur in the adult fertile population aged 15-49 years. According to UNAIDS, Vietnam had a national HIV prevalence of 0.3% of the total population at the end of 2019, with approximately 230,000 PLHIV. The most effective way to prevent mother-to-child transmission of HIV is ART to reduce maternal viral load. HIV-infected pregnant women should undergo monthly monitoring, especially before the expected date of delivery. The aim of our work was to analyze subtypic structure and drug-resistant variants of HIV in pregnant women in Ho Chi Minh City. The study material was blood plasma samples from HIV-infected pregnant women: 31 women showed virological failure of ART, and 30 women had not previously received therapy. HIV-1 genotyping and mutation detection were performed based on analysis of the nucleotide sequences of the pol gene region. More than 98% of sequences genotyped as HIV-1 sub-subtype CRF01_AE. When assessing the occurrence of drug resistance mutations, genetic resistance to any drug was detected in 74.41% (95% CI: 62.71-85.54%) of patients. These included resistance mutations to protease inhibitors in 60.66% (95% CI: 47.31-72.93%) of patients, to NRTIs in 8.20% (95% CI: 2.72-18.10%), and to NNRTIs in 44.26% (95% CI: 31.55-57.52%). Mutations associated with NRTI (2) and NNRTI (8) resistance as well as PI mutations (12), including minor ones, were identified. The high prevalence of drug resistance mutations found in this study among pregnant women, both in therapeutically naive individuals and in patients with virological failure of ART, indicates that currently used regimens in Vietnam are insufficient to prevent vertical HIV infection.

Features of the Neonatal Period in Perinatally HIV-Exposed Children Receiving Combined Сhemoprophylaxis of mother-to-child Transmission of HIV

The aim. To study the features of the course of the neonatal period in children, perinatally exposed to HIV, who receive an enhanced regimen of chemoprophylaxis of HIV mother-to-child transmission.Patients and methods. A retrospective longitudinal cohort study of mother – child pairs for the period from 2017 to 2019 was carried out. The clinical observation group included HIV-positive women with a high risk of vertical transmission of the immunodeficiency virus (n = 213) and their newborn children (n = 214), who were prescribed an enhanced chemoprophylaxis regimen of HIV transmission from mother to child. Results. According to the results of the study of HIV-positive mothers we revealed a high prevalence of secondary diseases and a high per partum viremia – 1700 (222–18342) copies/ml. 35.9 % of children were born prematurely, 27.5 % – had low birth weight by gestational age. In newborns, diseases of the respiratory (24.3 %) and nervous (17.2 %) systems prevailed. 17.2 % of children developed intrauterine infection; HIV RNA was detected in 3.7 %. Congenital malformations were observed in 7.4 % of children. Symptoms of enteropathy were noted in 24.7 % of newborns. A decrease in red blood counts was found in all children by the 28th day of life (pw < 0.001).Conclusion. The study confirms the need for increased attention and improvement of approaches to medical support of children who were perinatally exposed to high risk of vertical HIV infection.

Understanding Viral and Immune Interplay During Vertical Transmission of HIV: Implications for Cure.

Despite the significant progress that has been made to eliminate vertical HIV infection, more than 150,000 children were infected with HIV in 2019, emphasizing the continued need for sustainable HIV treatment strategies and ideally a cure for children. Mother-to-child-transmission (MTCT) remains the most important route of pediatric HIV acquisition and, in absence of prevention measures, transmission rates range from 15% to 45% via three distinct routes: in utero, intrapartum, and in the postnatal period through breastfeeding. The exact mechanisms and biological basis of these different routes of transmission are not yet fully understood. Some infants escape infection despite significant virus exposure, while others do not, suggesting possible maternal or fetal immune protective factors including the presence of HIV-specific antibodies. Here we summarize the unique aspects of HIV MTCT including the immunopathogenesis of the different routes of transmission, and how transmission in the antenatal or postnatal periods may affect early life immune responses and HIV persistence. A more refined understanding of the complex interaction between viral, maternal, and fetal/infant factors may enhance the pursuit of strategies to achieve an HIV cure for pediatric populations.

Robust HIV-specific CD4+ and CD8+ T-cell responses distinguish elite control in adolescents living with HIV from viremic nonprogressors.

Background:Elite controllers are therapy-naive individuals living with HIV capable of spontaneous control of plasma viraemia for at least a year. Although viremic nonprogressors are more common in vertical HIV-infection than in adults’ infection, elite control has been rarely characterized in the pediatric population.Design:We analyzed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four pediatric elite controllers (PECs) compared with age-matched nonprogressors (PNPs), progressors and HIV-exposed uninfected (HEUs) adolescents.Results:PECs T-cell populations had lower immune activation and exhaustion levels when compared with progressors, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterized by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared with PNPs and progressors. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B∗27/57/81.Conclusion:Pediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell mediated immune control of viremia, and in adult elite controllers, low immune activation is therefore the consequence of the rapid CD8+ T-cell mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in posttreatment controllers, in whom protective HLA-I molecules are not the main factor.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES:To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC).METHODS:HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits.RESULTS:The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells.CONCLUSION:The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Effect of a Nutritional Intervention on the Intestinal Microbiota of Vertically HIV-Infected Children: The Pediabiota Study.

Aims: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. Methods: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3–V4 region of the 16S rRNA gene was sequenced in fecal samples. Results: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. Conclusions: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. Summary: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.

The IMpact of Vertical HIV infection on child and Adolescent SKeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study

IntroductionThe scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a...

Left Ventricular Function, Epicardial Adipose Tissue, and Carotid Intima-Media Thickness in Children and Adolescents With Vertical HIV Infection.

Life expectancy of HIV patients has increased considerably as a result of antiretroviral therapy (ART), and cardiovascular (CV) disease has emerged as an important late concern. People with HIV infection could have an impaired systolic function; however data on diastolic function and markers of CV risk, such as epicardial adipose tissue (EAT) and intima-media thickness (IMT), are lacking. Aim of this study is to evaluate left ventricular function, EAT, and IMT in children and adolescents with vertically acquired HIV infection. We enrolled 29 subjects on ART (13, 45% men; median age of 13.0, and interquartile range 9-18), and 29 age-matched controls. All patients and controls underwent echocardiographic evaluation, with study of the systolic and diastolic function and measurement of the EAT, and a carotid ultrasound study for IMT measurement. Comparing HIV-infected patients to healthy controls, we found a statistically significant increase of EAT and IMT (mean ± SD) (EAT: 3.16 ± 1.05 vs 1.24 ± 0.61 mm; P < 0.0001. IMT: 0.77 ± 0.15 vs 0.51 ± 0.11 mm; P < 0.0001), and a significant reduction of ejection fraction, evaluated with the biplane Simpson method (mean ± SD) (58.5% ± 6.66% vs 66% ± 4.24%; P = 0.029). These results are not related with age, gender, degree of lipodystrophy, dyslipidemia, hyperinsulinism, and ART duration or the use of single antiretroviral classes. Vertically infected HIV children and adolescents show an increased thickness of EAT and IMT, expression of potentially increased CV risk. They also show an impaired systolic function.

Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence.

We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. Lower CD4 T cells and higher T cell activation and exhaustion markers were noted on CD4 T and on CD8 T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4 T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4 T and CD8 T subsets was detected. Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia.

I-106 Early treatment initiation in children with vertical HIV infection influences HIV specific immune responses

Background: Despite successes in prevention of mother to child HIV transmission (MTCT), issues related to early diagnosis, ART initiation and adherence play a role in the disease course of HIV infected children. Early ART initiation in HIV infected infants leads to reduced size of HIV reservoirs and curtails clinical progression but role of the immune system in this process is not well understood. With early initiation of ART, HIV infected infants preserve their CD4+ T cells and in some instances remain seronegative for HIV due to limited exposure of B cells to HIV antigen. We are performing immunologic assessments in the HIV Exposed Pediatric Patients (HEPP) Project and discuss a group of children from Rome, Italy. The goal of the present study is to evaluate HIV-specific immunity of vertically HIV infected children in relation to timing of ART initiation. Methods: The study group consists of older vertically infected HIV+ children and adolescents who initiated ART at different ages after birth and have maintained durable viral control (plasma HIV-RNA &lt;50 cp/mL). Immunologic studies were performed in 27 children (at ages 2.1–15.7 yrs) of whom 22 had started ART early, at age &lt;6 mo [early treated (ET)] and 5 who started ART later, at age &gt;2 yrs [late treated (LT)] with ET experiencing longer duration of ART (P &lt; 0.05) at the time of study. ET children were also evaluated by HIV serology (Abbott Architect HIV Ag/Ab Combo Assay) to establish if they were seropositive (SP) or seronegative (SN) to HIV. Flow cytometry was performed using BD LSRFortessa for T cells and BD FACS Aria II for B cells. HIV-gag specific CD4+ and CD8+ T cells were investigated by flow cytometry in cryopreserved PBMC for the induction of intracellular cytokines (IL-2, IFN-g, TNF, IL-21) in CD40L+ CD4+ T cells and intracellular cytokines (IL-2, IFN-g, TNF) as well as Perforin, Granzyme B and CD107a in CD69+ CD8+ T cells following 12 hours stimulation with HIV gag PTE peptides. In addition, Env-specific CD4+ T cells were evaluated following 12 hours stimulation of PBMC with Env peptides. IgD+ and IgM+ B cell subsets were determined in gp140+ B cells. Moreover, env-specific and non-specific B cells were sorted to perform transcriptomic analysis with Fluidigm (Biomark). Differences between groups were determined by unpaired or Mann-Whitney t tests if the data were normally distributed or not, respectively. Results: In this group of HIV+ children, frequencies of HIV gag-specific CD4+ T cells and CD8+ T cells were similar between ET and LT but differed qualitatively. Gag stimulated CD4+ T cells of ET exhibited higher proportions of IL-21 and IFNg with enrichment of polyfunctional T cells defined by the simultaneous presence of 3 or more cytokines. Gag stimulated CD8+ T cells of ET exhibited higher frequencies of cytotoxic cells (CD107a+Perf+GrzB+). In ET, serologic evaluation of HIV Ab revealed 6/22 (27.3%) to be SN. The gp140-specific CD4+ T cell frequencies were similar in SN and SP but intracellular IL-21 expression was higher in SP. Frequencies of gp140+ CD19+ B cells were similar between SN and SP, but HIV-specific CD27+ memory B cells were predominantly IgM+ in SN while in SP, the gp140+CD27+ memory B cells were enriched in IgD-cells. Gene expression signatures in gp140+IgM+ cells revealed upregulation of genes involved in both plasma cell differentiation (PRDM1) and GC reaction (BCL6) only in SP after in-vitro stimulation. Conclusions: Time of ART initiation after birth has a long-term impact on the quality of the host HIV-specific immune responses in vertically infected HIV+ children with durable virus suppression. Earlier ART initiation is associated with preserved HIV gag-specific CD4+ and CD8+ T cells. Moreover, even in those who become seronegative for HIV, the HIV Env-specific CD4+ T cells and B cells persist, the latter demonstrating a blunted differentiation with enrichment of IgM+ B cells. ET children with consistent viral control are prime candidates for therapeutic approaches aimed at permanent remission of HIV. These studies are supported by ViiV Health Care grant to EPIICAL and NIH grant AI127347 to SP.

Economic incentives for HIV testing by adolescents in Zimbabwe: a randomised controlled trial

SummaryBackgroundHIV testing is the important entry point for HIV care and prevention service, but uptake of HIV testing and thus coverage of antiretroviral therapy are much lower in older children and adolescents than in adults. We investigated the effect of economic incentives provided to caregivers of children aged 8–17 years on uptake of HIV testing and counselling in Harare, Zimbabwe.MethodsThis randomised controlled trial was nested within a household HIV prevalence survey of children aged 8–17 years in Harare. Households with one or more survey participants whose HIV status was unknown were eligible to participate in the trial. Eligible households were randomly assigned (1:1:1) to either receive no incentive, receive a fixed US$2 incentive, or participate in a lottery for $5 or $10 if the participant presented for HIV testing and counselling at a local primary health-care centre. The survey fieldworkers who enrolled participants were not blinded to trial arm allocation, but the statistician was blinded for analysis of outcome. The primary outcome was the proportion of households in which at least one child had an HIV test within 4 weeks of enrolment. HIV test uptake in the incentivised groups was compared with uptake in the non-incentivised group using logistic regression, adjusting for community and number of children as fixed effects and research assistant as a random effect. All analyses were by intention to treat. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201605001615280.FindingsBetween Aug 4, and Dec 18, 2015, 2050 eligible households were enrolled in the prevalence survey. 649 (32%) households were assigned no incentive, 740 (34%) households were assigned a $2 incentive, and 661 (32%) households were assigned to lottery participation. Children were unavailable in 148 households in the no-incentive group, 63 households in the $2 incentive group, and 81 households in the lottery group. 1688 households had at least one child with unknown HIV status and were enrolled into the trial. 22 households had no undiagnosed child, and one household refused consent. The primary outcome of HIV testing was assessed in 472 (28%) households in the no-incentive group, 654 (39%) households in the $2 incentive group, and 562 (33%) households in the lottery group. At least one child was HIV tested in 93 (20%) households in the no-incentive group, in 316 (48%) households in the $2 incentive group (adjusted odds ratio 3·67, 95% CI 2·77–4·85; p<0·0001), and in 223 (40%) of 562 households in the lottery group (2·66, 2·00–3·55; p<0·0001). No adverse events were reported.InterpretationFixed incentives and lottery-based incentives increased the uptake of HIV testing by older children and adolescents, a key hard-to-reach population. This strategy would be sustainable in the context of vertical HIV infection as repeated testing would not be necessary until sexual debut.FundingWellcome Trust.

Zaburzenia neurologiczne u dzieci wertykalnie zakażonych HIV

IntroductionThe risk of CNS changes in vertical HIV infection is high. The frequency and severity of disorders are connected to disease stage, the age of first symptoms, progression, child's actual age and medications’ neurotoxicity. The aim of the studyThe aim of the study is to identify and determine the frequency of neurological disorders, and to identify factors influencing the occurrence of those disorders. Materials and MethodsThe study was retrospective and partially prospective. It included 67 children vertically infected with HIV, aged from 2 months to 20 years of age. Neurological disorders were assessed by physical examination, including a detailed neurological examination. In the study, virological laboratory tests (VL HIV RNA) and percentage of CD4+T lymphocytes (immunological classification) were analyzed. ResultsAbnormal neurological examination was observed in 18 patients. In 10 of the 18 patients, neurological disorders were found in their first year of life. The most common neurological complication was HIV encephalopathy (HE). ConclusionThe occurrence of neurological disorders is influenced by the degree of immunodeficiency, HIV viral load at diagnosis, and age of initiation of ARV therapy. Starting ARV treatment <12 months of age has a neuroprotective effect.

Low Bone Mineral Density in Vertically HIV-infected Children and Adolescents: Risk Factors and the Role of T-cell Activation and Senescence.

Our aim was to determine the prevalence and risk factors associated with low bone mineral density (BMD) in vertically HIV-infected patients and to investigate whether low BMD is related to immune activation and senescence induced by HIV infection. A cross-sectional study was performed in 98 vertically HIV-infected patients. BMD was measured by dual-energy radiograph absorptiometry at lumbar spine. Height adjustment of BMD Z score was performed using height-for-age Z score. T-cell immune activation and senescence were analyzed in a subgroup of 54 patients by flow cytometry. Median age was 15.9 years, 71.4% were Caucasian, 99% received antiretroviral therapy and 80.6% had undetectable viral load. Low BMD (BMD Z score ≤ -2) was present in 15.3% of cases, but after height adjustment in 4.1% of cases. Height-adjusted BMD Z score was positively correlated with body mass index Z score, CD4/CD8 ratio and nadir CD4, and inversely with duration of severe immunosuppression and parathyroid hormone values. In the multivariate model including age, gender, ethnicity, encephalopathy, Tanner stage, nadir CD4, duration of viral suppression, CD4 count, CD4/CD8 ratio, body mass index, cumulative duration of antiretroviral therapy, tenofovir and protease inhibitors exposure, nadir CD4 was independently associated to height-adjusted BMD Z score. No association was found between height-adjusted BMD Z score and T-cell activation or senescence. The prevalence of low BMD in vertically HIV-infected patients was low after height adjustment. Nadir CD4, but not T-cell activation or senescence, was an independent predictor for low BMD. Larger and prospective studies are needed to achieve better knowledge of the pathogenesis of low BMD in vertical HIV infection.

Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission.

Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen. Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3-8 mg/L]. Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32-41 weeks) and 2.9 kg (1.5-4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6-25.1 mg/L), 3.5 mg/L (1.6-6.8 mg/L), and 4.3 mg/L (0.1-19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg·h (0.01-0.50 L·kg·h) at week 2 to 0.18 L·kg·h (0.01-0.78 L·kg·h) at week 4. Increased drug exposure [area under the curve (AUCτ)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%). Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.

Ongoing Maternal-Child Transmission of HIV in an Urban Area, 2003-2012.

Mother-to-child transmission of HIV can be prevented by prenatal and peripartum interventions. We sought to determine the prevalence of vertical HIV transmission in an urban cohort of HIV-exposed infants and describe cases of vertical HIV infection presenting during and after the neonatal period. This retrospective cohort study included HIV-exposed infants born between July 1, 2003, and June 30, 2012, who received care at an urban referral site. There were 516 infants with HIV exposure known by the time of delivery; 9 of these infants (1.7%; 95% confidence interval: 0.8%-3.3%) were HIV infected. The HIV infection rate was 0.7% for those receiving prenatal antiretroviral (ARV) therapy and 9.3% for those receiving only intrapartum and/or postnatal ARV therapy. Among those diagnosed with HIV at delivery, 46% received no prenatal care. Our data suggest that strategies to eliminate infant HIV infections ought to include ensuring better access to prenatal care, HIV testing, and ARV therapy initiation during pregnancy.

Analysis of miRNA–mRNA expression profiles in decidual natural killer cells during early pregnancy

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 17 LPS stimulation induced a significant increase of transcript levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9, while P4 treatment significantly attenuated LPSinduced increase of transcript levels of these MMPs. Conclusions: Our preliminary results suggest that P4 might prevent spontaneous preterm labor by inhibiting cervical remodeling, particularly through the attenuation of ECM degradation by inhibiting MMPs production. http://dx.doi.org/10.1016/j.jri.2014.09.040 Analysis of miRNA–mRNA expression profiles in decidual natural killer cells during early pregnancy D. Zhao1,∗, B. Than Naing1, K. Inada2, T. Shima2, S. Saito2, T. Takeshita3, T. Takizawa1 1 Department of Molecular Medicine & Anatomy, Nippon Medical School, Tokyo, Japan 2 Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan 3 Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan Objective: Decidual natural killer (dNK) cells play an important role in the maintenance of early pregnancy. However, the expression profiles and functions of miRNAs within dNK cells remain to be clarified.We investigated the miRNA–mRNAexpressionprofiles in dNK cells during early pregnancy. Methods:Decidual tissue and peripheral blood samples from patients who gave informed consent were aseptically obtained after legal abortions (at 6–7 weeks of gestation, n=3). We compared miRNA-mRNA expression patterns between dNK and peripheral NK (pNK) cells. The expression levels of miRNAs were examined by real-time PCR using a TaqMan microRNA Assay, and gene expression profiling was conducted using an Agilent microarray. Networks, functions, and pathways analyses were generated using Ingenuity Pathway Analysis (IPA). Results and conclusions: Among the 750 miRNAs examined, 199 miRNAs were significantly up-regulated in dNK cells compared with pNK cells. We detected some placenta-specific miRNAs derived from the chromosome 19 microRNA cluster in dNK cells. Among the 34,127 transcripts examined, 534 genes were significantly downregulated in dNK cells compared with pNK cells; the down-regulated gene expression profile exhibited low cytotoxicity in dNK cells. Some of the up-regulated miRNAs in dNK cells were the miRNAs potentially targeting the above cytotoxicity-associated genes. These data suggest that dNKcells have auniquemiRNA-mRNA interaction network for the maintenance of early pregnancy. http://dx.doi.org/10.1016/j.jri.2014.09.041 Frequent Chlamydophila pneumoniae infection in vertically HIV-infected children in Vietnam Q.D. Trinh ∗, N.T. Pham, N.T. Le Nguyen, B.Q. Lam, K.T. Le Phan, K.H. Truong, T.Q. Le, H.T. Nguyen, T.C. Tang, Y. Izumi, S. Komine-Aizawa, H. Ushijima, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Chlamydophila pneumoniae (C. pneumoniae) is an intracellular pathogen and often cause fatal respiratory symptoms in HIV/AIDS patients. However, its frequency in children with vertical HIV infection is so far unknown. Methods: A total of 89 blood samples collected from HIV-infected infants and children from provinces of southern Vietnam who were hospitalized at Children’s Hospital 1, Ho Chi Minh City, during the 1-year period fromOctober 2004 to September 2005 were submitted to serological screening for IgG, IgA, and IgM antibodies against C. pneumoniae. The presence of this microorganism was also evaluated by PCR. Age matched control enrolled HIV negative 91 children with other infectious disorders. Results: The results showed that 64% of the samples were positive for anti-C. pneumoniae IgG, 31.5% were positive for IgA, and 3.4% were positive for IgM. The highest prevalences of IgG and IgA positivity, 75% and 66.7%, respectively, were noted in the 1to 2-year-old age group. In control patients, IgG and IgA positivitywere 7.7 and 4.4% respectively. No patients showed positive PCR results. Conclusions: Our study revealed a high seroprevalence of C. pneumoniae in Vietnamese infants and children with HIV/AIDS by vertical transmission. http://dx.doi.org/10.1016/j.jri.2014.09.042 Porphyromonas gingivalis inhibits trophoblast invasion N. Hirohata ∗, S. Komine-Aizawa, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Periodontitis has been regarded as a risk factor of pregnancy complications including preterm birth, intrauterine growth retardation and preeclampsia. However protective roles of dental intervention during pregnancyon fetal/maternal outcomes are controversial. In this study, we investigated in vitro effects of a periodontal bacteria Porphyromonas gingivalis on cultured trophoblasts and mucosal natural killer cells to mimic in vivo phenomena at the feto-maternal interface. Methods: 2×109 of P. gingivalis (ATCC33277)were cultured at 37 ◦C, 10% CO2 in BHIB media supplemented with 0.005mgml−1 hemin and 0.0005mgml−1 menadione for

Progesterone transcriptionally inhibits LPS-induced matrix metalloproteinase up-regulation in human cervical fibroblast cells

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 17 LPS stimulation induced a significant increase of transcript levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9, while P4 treatment significantly attenuated LPSinduced increase of transcript levels of these MMPs. Conclusions: Our preliminary results suggest that P4 might prevent spontaneous preterm labor by inhibiting cervical remodeling, particularly through the attenuation of ECM degradation by inhibiting MMPs production. http://dx.doi.org/10.1016/j.jri.2014.09.040 Analysis of miRNA–mRNA expression profiles in decidual natural killer cells during early pregnancy D. Zhao1,∗, B. Than Naing1, K. Inada2, T. Shima2, S. Saito2, T. Takeshita3, T. Takizawa1 1 Department of Molecular Medicine & Anatomy, Nippon Medical School, Tokyo, Japan 2 Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan 3 Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan Objective: Decidual natural killer (dNK) cells play an important role in the maintenance of early pregnancy. However, the expression profiles and functions of miRNAs within dNK cells remain to be clarified.We investigated the miRNA–mRNAexpressionprofiles in dNK cells during early pregnancy. Methods:Decidual tissue and peripheral blood samples from patients who gave informed consent were aseptically obtained after legal abortions (at 6–7 weeks of gestation, n=3). We compared miRNA-mRNA expression patterns between dNK and peripheral NK (pNK) cells. The expression levels of miRNAs were examined by real-time PCR using a TaqMan microRNA Assay, and gene expression profiling was conducted using an Agilent microarray. Networks, functions, and pathways analyses were generated using Ingenuity Pathway Analysis (IPA). Results and conclusions: Among the 750 miRNAs examined, 199 miRNAs were significantly up-regulated in dNK cells compared with pNK cells. We detected some placenta-specific miRNAs derived from the chromosome 19 microRNA cluster in dNK cells. Among the 34,127 transcripts examined, 534 genes were significantly downregulated in dNK cells compared with pNK cells; the down-regulated gene expression profile exhibited low cytotoxicity in dNK cells. Some of the up-regulated miRNAs in dNK cells were the miRNAs potentially targeting the above cytotoxicity-associated genes. These data suggest that dNKcells have auniquemiRNA-mRNA interaction network for the maintenance of early pregnancy. http://dx.doi.org/10.1016/j.jri.2014.09.041 Frequent Chlamydophila pneumoniae infection in vertically HIV-infected children in Vietnam Q.D. Trinh ∗, N.T. Pham, N.T. Le Nguyen, B.Q. Lam, K.T. Le Phan, K.H. Truong, T.Q. Le, H.T. Nguyen, T.C. Tang, Y. Izumi, S. Komine-Aizawa, H. Ushijima, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Chlamydophila pneumoniae (C. pneumoniae) is an intracellular pathogen and often cause fatal respiratory symptoms in HIV/AIDS patients. However, its frequency in children with vertical HIV infection is so far unknown. Methods: A total of 89 blood samples collected from HIV-infected infants and children from provinces of southern Vietnam who were hospitalized at Children’s Hospital 1, Ho Chi Minh City, during the 1-year period fromOctober 2004 to September 2005 were submitted to serological screening for IgG, IgA, and IgM antibodies against C. pneumoniae. The presence of this microorganism was also evaluated by PCR. Age matched control enrolled HIV negative 91 children with other infectious disorders. Results: The results showed that 64% of the samples were positive for anti-C. pneumoniae IgG, 31.5% were positive for IgA, and 3.4% were positive for IgM. The highest prevalences of IgG and IgA positivity, 75% and 66.7%, respectively, were noted in the 1to 2-year-old age group. In control patients, IgG and IgA positivitywere 7.7 and 4.4% respectively. No patients showed positive PCR results. Conclusions: Our study revealed a high seroprevalence of C. pneumoniae in Vietnamese infants and children with HIV/AIDS by vertical transmission. http://dx.doi.org/10.1016/j.jri.2014.09.042 Porphyromonas gingivalis inhibits trophoblast invasion N. Hirohata ∗, S. Komine-Aizawa, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Periodontitis has been regarded as a risk factor of pregnancy complications including preterm birth, intrauterine growth retardation and preeclampsia. However protective roles of dental intervention during pregnancyon fetal/maternal outcomes are controversial. In this study, we investigated in vitro effects of a periodontal bacteria Porphyromonas gingivalis on cultured trophoblasts and mucosal natural killer cells to mimic in vivo phenomena at the feto-maternal interface. Methods: 2×109 of P. gingivalis (ATCC33277)were cultured at 37 ◦C, 10% CO2 in BHIB media supplemented with 0.005mgml−1 hemin and 0.0005mgml−1 menadione for

Frequent Chlamydophila pneumoniae infection in vertically HIV-infected children in Vietnam

s for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20 17 LPS stimulation induced a significant increase of transcript levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9, while P4 treatment significantly attenuated LPSinduced increase of transcript levels of these MMPs. Conclusions: Our preliminary results suggest that P4 might prevent spontaneous preterm labor by inhibiting cervical remodeling, particularly through the attenuation of ECM degradation by inhibiting MMPs production. http://dx.doi.org/10.1016/j.jri.2014.09.040 Analysis of miRNA–mRNA expression profiles in decidual natural killer cells during early pregnancy D. Zhao1,∗, B. Than Naing1, K. Inada2, T. Shima2, S. Saito2, T. Takeshita3, T. Takizawa1 1 Department of Molecular Medicine & Anatomy, Nippon Medical School, Tokyo, Japan 2 Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan 3 Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan Objective: Decidual natural killer (dNK) cells play an important role in the maintenance of early pregnancy. However, the expression profiles and functions of miRNAs within dNK cells remain to be clarified.We investigated the miRNA–mRNAexpressionprofiles in dNK cells during early pregnancy. Methods:Decidual tissue and peripheral blood samples from patients who gave informed consent were aseptically obtained after legal abortions (at 6–7 weeks of gestation, n=3). We compared miRNA-mRNA expression patterns between dNK and peripheral NK (pNK) cells. The expression levels of miRNAs were examined by real-time PCR using a TaqMan microRNA Assay, and gene expression profiling was conducted using an Agilent microarray. Networks, functions, and pathways analyses were generated using Ingenuity Pathway Analysis (IPA). Results and conclusions: Among the 750 miRNAs examined, 199 miRNAs were significantly up-regulated in dNK cells compared with pNK cells. We detected some placenta-specific miRNAs derived from the chromosome 19 microRNA cluster in dNK cells. Among the 34,127 transcripts examined, 534 genes were significantly downregulated in dNK cells compared with pNK cells; the down-regulated gene expression profile exhibited low cytotoxicity in dNK cells. Some of the up-regulated miRNAs in dNK cells were the miRNAs potentially targeting the above cytotoxicity-associated genes. These data suggest that dNKcells have auniquemiRNA-mRNA interaction network for the maintenance of early pregnancy. http://dx.doi.org/10.1016/j.jri.2014.09.041 Frequent Chlamydophila pneumoniae infection in vertically HIV-infected children in Vietnam Q.D. Trinh ∗, N.T. Pham, N.T. Le Nguyen, B.Q. Lam, K.T. Le Phan, K.H. Truong, T.Q. Le, H.T. Nguyen, T.C. Tang, Y. Izumi, S. Komine-Aizawa, H. Ushijima, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Chlamydophila pneumoniae (C. pneumoniae) is an intracellular pathogen and often cause fatal respiratory symptoms in HIV/AIDS patients. However, its frequency in children with vertical HIV infection is so far unknown. Methods: A total of 89 blood samples collected from HIV-infected infants and children from provinces of southern Vietnam who were hospitalized at Children’s Hospital 1, Ho Chi Minh City, during the 1-year period fromOctober 2004 to September 2005 were submitted to serological screening for IgG, IgA, and IgM antibodies against C. pneumoniae. The presence of this microorganism was also evaluated by PCR. Age matched control enrolled HIV negative 91 children with other infectious disorders. Results: The results showed that 64% of the samples were positive for anti-C. pneumoniae IgG, 31.5% were positive for IgA, and 3.4% were positive for IgM. The highest prevalences of IgG and IgA positivity, 75% and 66.7%, respectively, were noted in the 1to 2-year-old age group. In control patients, IgG and IgA positivitywere 7.7 and 4.4% respectively. No patients showed positive PCR results. Conclusions: Our study revealed a high seroprevalence of C. pneumoniae in Vietnamese infants and children with HIV/AIDS by vertical transmission. http://dx.doi.org/10.1016/j.jri.2014.09.042 Porphyromonas gingivalis inhibits trophoblast invasion N. Hirohata ∗, S. Komine-Aizawa, S. Hayakawa Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Japan Objective: Periodontitis has been regarded as a risk factor of pregnancy complications including preterm birth, intrauterine growth retardation and preeclampsia. However protective roles of dental intervention during pregnancyon fetal/maternal outcomes are controversial. In this study, we investigated in vitro effects of a periodontal bacteria Porphyromonas gingivalis on cultured trophoblasts and mucosal natural killer cells to mimic in vivo phenomena at the feto-maternal interface. Methods: 2×109 of P. gingivalis (ATCC33277)were cultured at 37 ◦C, 10% CO2 in BHIB media supplemented with 0.005mgml−1 hemin and 0.0005mgml−1 menadione for

Vertical HIV infection is preventable but remains challenging

The frequency of HIV mother-to-child transmission in Switzerland is nowadays < 1 %, if the pregnant woman receives successful anti-HIV treatment and the newborn apt post-exposure prophylaxis (PEP) and is not breast-fed. The interdisciplinary approach in arranging the maternal anti-HIV treatment, birth mode and PEP for the child is essential. Nevertheless, HIV infection in the child needs to be considered when it presents with compatible signs and symptoms, as HIV infection of the mother may escape diagnosis.