Perinatal HIV Infection Research Articles

School functioning of children with perinatal HIV-infection in high-income countries: A systematic review.

IntroductionSince the introduction of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection is a manageable chronic disease. However, school-age children (4–18 years) living with HIV could still experience problems with functioning at school, due to the impact of the virus itself, medication, comorbidities and social stigma. School functioning covers academic achievement, school attendance, and social relationships and is of utmost importance to optimize normal participation.MethodsTo gain insight in school functioning problems of perinatally HIV-infected children, we performed a systematic review of the literature in multiple databases from January 1997 up to February 2019. Studies were included if they described outcomes of school functioning of school-age children perinatally infected with HIV, in high-income countries. Meta-analyses were performed for sufficiently comparable studies.Results and discussionResults from 32 studies show that HIV-infected children experience more problems in various areas of school functioning in comparison with national norms, matched healthy controls, siblings and HIV-exposed uninfected (HEU) children. The most pronounced differences concerned the usage of special educational services, general learning problems, and mathematics and reading performance scores. Comparisons with both national norms and siblings/HEU children show that the differences between HIV-infected children and siblings/HEU children were less pronounced. Moreover, siblings/HEU children also reported significantly worse outcomes compared to national norms. This suggests that problems in school functioning cannot be solely attributed to the HIV-infection, but that multiple socio-economic and cultural factors may play a role herein.ConclusionPerinatally HIV-infected children seem vulnerable to problems in various areas of school functioning. Therefore, monitoring of school functioning should be an important aspect in the care for these children. A family-focused approach with special attention to a child’s socio-environmental context and additional attention for siblings and HEU children, is therefore recommended.

Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection

Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation.

MRI of perinatal HIV infection in the era of antiretroviral therapy

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Third-trimester repeat HIV testing: it is time we make it universal

Since the 1990s, perinatal transmission of HIV has decreased substantially, largely as a result of improved detection secondary to routine HIV screening in pregnancy and the use of antiretroviral therapy. However, despite reductions in HIV transmission, elimination of perinatal transmission, defined as an incidence of perinatal HIV infection of <1 per 100,000 live births and a transmission rate of <1%, remains elusive. An estimated 80% of perinatal transmissions occur after 36 weeks' gestation, which highlights the importance of diagnosis and treatment of maternal HIV infection before the highest-risk period for perinatal transmission. With timely identification of seroconversion, intrapartum and neonatal interventions can lower the risk of perinatal transmission from 25% to 10%, substantially reducing perinatal transmission events. The American College of Obstetricians and Gynecologists and the Centers for Disease Control and Prevention recommend that routine HIV testing be performed in all pregnancies, as early in the prenatal course as possible. Third-trimester repeat testing is only recommended for individuals known to be at high risk of acquiring HIV (ie, those who are incarcerated; who reside in jurisdictions with elevated HIV incidence; who are receiving care in facilities that have an HIV incidence in pregnant women > 1 per 1000 per year; or have signs or symptoms of acute HIV). However, among reproductive-age women, heterosexual intercourse is the most common mode of HIV transmission, and the risk of HIV seroconversion is greater during pregnancy than outside of pregnancy. Furthermore, state statutes for HIV testing in pregnancy are largely lacking. In this clinical opinion, we reviewed the evidence in support of universal third-trimester repeat HIV testing in pregnancy using a successful state-mandated testing program in Illinois. In addition, we provided clinical recommendations to further reduce missed perinatal transmission cases by implementing universal third-trimester repeat testing, obtaining hospital buy-in, monitoring testing adherence, bridging communications across multidisciplinary teams, and engaging clinicians in advocacy work.

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood.

Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan–Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19–23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: −0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = −0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.

Second-generation mother-to-child HIV transmission in South Africa is characterized by poor outcomes.

The worldwide incidence of pregnancy for women living with perinatal HIV infection is increasing. Subsequently, there is growing risk of second-generation mother-to-child HIV transmission. The infant clinical outcomes for such a phenomenon have yet to be described. As part of a wider observational study in KwaZulu-Natal, South Africa, six infants with in-utero HIV infection were identified as being born to mothers with perinatal HIV infection. Blood results and clinical data were collected in the first 3 years of life. In two cases, sample availability allowed confirmation by phylogenetic analysis of grandmother-to-mother-to-child HIV transmission. Outcomes were poor in all six cases. All six mothers had difficulty administering twice daily combination antiretroviral therapy to their infants due to difficulties with acceptance, disclosure, poor health and being themselves long-term nonprogressors. Nonnucleoside reverse transcriptase inhibitor-resistant virus was detected in all mothers tested. None of the infants maintained suppression of viraemia on combination antiretroviral therapy. One infant died, and another was lost to follow-up. As the numbers of second-generation mother-to-child transmissions increase, it is important to highlight that this mother-infant dyad represents an extremely vulnerable group. In order for them to survive and thrive, these infants' mothers require their specific needs to be addressed and given intensive support.

Correlation between mandibular bone density, CD4 T-cells, and duration of HAART in HIV-infected children

Introduction: Perinatal HIV infection has decreased adverse bone health effects and mineral accrual. HIV-infected patients have a multifactorial origin, including HIV bone cell infections, inflammatory cytokine effects on osteoblast and osteoclast activity, and HAART. The research objective was to examine the correlation between the mandibular bone density and CD4 T-cells with HAART duration in HIV-infected children. Methods: The mandibular bone density in the HIV-infected pediatric population was evaluated using a panoramic radiograph. The research design was a cross-sectional and univariate regression analysis for the sampling method. Mandibular density analysis using Spearman and Pearson correlation and HAART duration using Kendall correlation. Thirty-five HIV-infected children and seventeen non-HIV-infected children were recruited. Results: This study showed the correlation between HIV and non-HIV infected children (p&lt;0.05). The correlation between CD4 T-cells and mandibular bone density was significant (p&lt;0.05). Long term HAART and mandibular bone density have a significant correlation (p&lt;0.001). This research showed correlations between mandibular bone density CD4 T-cells and duration of HAART in HIV-infected children. Conclusion: HIV-infected children require a regular mandibular cortical bone examination to detect the onset of osteopenia and osteoporosis to obtain appropriate therapy.

Alarming rates of virological failure and HIV-1 drug resistance amongst adolescents living with perinatal HIV in both urban and rural settings: evidence from the EDCTP READY-study in Cameroon.

Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location. A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL≥1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1. Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were<15%. In urban settings, the immunological failure (IF) rate (CD4 <250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression. Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging.

Executive function in HIV-affected children and adolescents: a systematic review and meta-analyses

ABSTRACT This review aimed to determine: whether EF is affected in children and adolescents (2–24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: CRD42017067813) was conducted using 11 electronic databases (01.01.1981–09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.

Plasma biomarker factors associated with neurodevelopmental outcomes in children with perinatal HIV infection and controlled viremia.

We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART). Longitudinal retrospective cohort study of children with controlled blood HIV replication. Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA <400 copies/ml for ≥9 months before initial assessment). Twenty-three plasma biomarkers were measured at onset of controlled viremia, week 0 (first neurodevelopmental assessment), and week 48 (second neurodevelopmental assessment). Factor analysis was conducted at each time point. Multivariable linear regressions assessed associations between factors and neurodevelopmental scores. Median age at week 0 was 7.0 years. Eighteen biomarkers loaded on six factors: a (L-10, IFNγ, IFNα2, IL-1β, IL-6, IP-10, TNFα); B (sCD163, sICAM-1, sVCAM-1, CRP); C (sE-selectin, sP-selectin); D [MIP-1β, vascular endothelial growth factor (VEGF)-A]; E (sCD14, CRP); and F (CX3CL1, MCP-1). Higher factor B scores were consistently associated with worse cognition and attention/impulsivity, and higher factor D scores with better attention/impulsivity. These results suggest a detrimental effect of increased endothelial cell activation (sICAM-1, sVCAM-1) and monocyte/macrophage scavenger function (sCD163) and a beneficial effect of increased CCR5 ligand and HIV entry blocker MIP-1β and angiogenesis stimulant-VEGF concentrations on the neurodevelopment of children with PHIV. The model that emerges is of vascular inflammation leading to neurodevelopmental deficits. The role of persistent HIV replication in the central nervous system also needs to be further explored.

Sexual Intercourse Initiation and Adolescent Behaviors of Youth Living with Perinatal HIV Infection in Thailand

Today, youth living with perinatal HIV (YLPHIV) have grown-up receiving antiretroviral treatment. We determine the frequency of sexual intercourse initiation and associated factors among YLPHIV in Thailand. YLPHIV age between 15 and < 25 years were recruited from either HIV clinics or the community via youth networks from Dec 2017 to Feb 2018. Data were collected using a self-administered questionnaire on a mobile device. The questionnaire included demographic and socioeconomic background, their lifetime sexual and adolescent behaviors, reasons for not having sexual intercourse, and future plans for sexual intercourse. Comparisons between sexes, age groups, and sexual experiences were made; logistic regression was used to identify associated factors. A total of 120 YLPHIV were enrolled; 58 (48%) were female. Their mean ± SD age and duration on ART were 20.3 ± 2.6 and 12.7 ± 3.0 years, respectively. Thirty-six (30%) reported having initiated sexual intercourse by the time of the study; 61 (51%) reported being in romantic relationships, and 58 (48%) reported having sexual contact. The only factor associated with sexual intercourse initiation based on the multivariate analysis was going out after midnight (odds ratio 3.968, 95% CI 1.540–10.226; p = 0.004). Among those who had not initiated sexual intercourse, the top three reasons for not initiating sexual intercourse were concern for their parents’ feelings (76%), not wanting to get sexually transmitted diseases (70%), and not wanting to spread HIV to others (62%). Half of YLPHIV who had not initiated sexual intercourse reported being uncertain whether, or when to have sex in the future. Sexual intercourse initiation and adolescent behaviors are part of growing-up for YLPHIV. Sexual education and HIV knowledge that are both age-appropriate and culturally appropriate should be included in HIV services, and counseling sessions to help these youths to plan for their future safely and responsibly.

The Role of Behavioral and Neurocognitive Functioning in Substance Use Among Youth with Perinatally Acquired HIV Infection and Perinatal HIV Exposure Without Infection.

This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand

BackgroundAdolescents living with perinatal HIV often experience difficult living circumstances that can impact educational achievement and thus their transition to adult life. We explored their school trajectories and evaluated the contribution of perinatal HIV-infection, in Thailand, where education is free and compulsory until the age of 15.MethodsWe used data from the Teens Living with Antiretrovirals (TEEWA) study, a cross-sectional case-control study conducted from 2011 to 2014 in Thailand. Participants were 707 adolescents living with perinatal HIV (ALPHIV, cases) aged 12–19 receiving antiretroviral therapy in 19 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected from the general population and individually matched for sex, age, and place of residence. School trajectory disruption was defined as ≥1 year of academic delay or as early school dropout (before 15 years of age). Logistic regression models were used to assess factors independently associated with disrupted school trajectory and to estimate the proportion of school disruption attributable to HIV-infection. We used multivariate imputations by chained equations (MICE) to manage missing data and performed two sensitivity analyses to evaluate the main model’s reliability.ResultsThe study population’s median age was 14.5 years (58% female). School trajectory disruption was experienced by 37% of ALPHIV and 12% of the controls. After adjusting for sociodemographic factors, ALPHIV were 5 times more likely to experience disruption than controls (ORA =5.2 [3.7–7.2]). About 50% of school trajectory disruption was attributable to HIV-infection. Males and adolescents living in institutions were more likely to experience school trajectory disruption (ORA =1.8 [1.3–2.4] and ORA =11.0 [7.7–15.8], respectively). Among ALPHIV, neurocognitive difficulties and growth delay were significantly associated with disruption (ORA =3.3 [2.1–5.2] and ORA =1.8 [1.3–2.6], respectively). For those living in families, disruption was also associated with having a caregiver who had less than a secondary-level education (ORA =2.1 [1.1–3.9]) or having experienced stigmatization (ORA =1.9 [1.2–3.1]).ConclusionsHIV and contextual factors combine to aggravate the educational disadvantage among ALPHIV. The impact of this disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be further explored.

Absence of Antenatal Care and Antiretroviral Therapy Associated with Preterm Delivery in Women with HIV: An 11-Year Retrospective Cohort in South Carolina.

Our primary aim was to determine if combined antiretroviral therapy (cART) increased the risk of poor infant outcomes among women with HIV. Maternal antiretroviral regimens were classified as mono-(mARV), dual (dARV), cART, and no ARV. Differences in dichotomous outcomes were compared using χ2 tests and continuous outcomes were compared using Kruskal-Wallis tests. Predictors of preterm delivery (PTD), low birth weight, and perinatal HIV infection were determined using logistic regression. During the 11-year study period, 643 mother-baby pairs with HIV exposure were eligible for analysis. Non-Hispanic, Black women were more likely to report mARV or no ARV use (p=.03). Women not taking ARVs were more likely to have PTD (p=.01). Prenatal care was associated with a reduction in PTD [aOR 0.12 (95% CI 0.03-0.5)] and perinatal HIV infection [aOR 0.1 (95% CI 0.01-0.7)]. Maternal cART and race were not associated with PTD. Rather, absence of prenatal care and lack of ARV use during pregnancy increased the risk of PTD and perinatal HIV infection.

Хронический гепатит С у детей с ВИЧ-инфекцией: особенности течения, успехи противовирусной терапии

Objective. To analyze the course of chronic hepatitis C (CHC) and efficacy of its treatment in children with HIV infection. Patients and methods. This study included 29 children aged 12 to 17 years (mean age 15.1 ± 0.2 years) with perinatal HIV infection and CHC. HIV stages were distributed as follows: stage 4A in 24 individuals (82.8%), stage 4B in 4 individuals (13.8%), and stage 4B in 1 individual (3.4%). All 29 patients received antiretroviral therapy. The distribution of children by HCV genotypes was as follows: 1a in one child (3.4%), 1b in 12 children (41.4%), and 3a in 16 children (55.2%). Antiviral therapy for CHC included glecaprevir/pibrentasvir (3 tablets; 100 mg + 40 mg) once a day for 56 days. Data analysis was performed using the Statistica for Windows software (version 10.0). Results. The mean HCV RNA level was 595,666 ± 34,734 IU/mL (range: 1,100–3,863,025 IU/mL). After 4, 8, or 12 weeks of antiviral therapy for HCV, HCV RNA clearance was achieved in all study participants (p = 0.01). Before treatment initiation, mean CD4+ count was 738 ± 34 cells/μL (above 500 cells/μL), which indicated the absence of immunodeficiency in the group analyzed. Successful antiviral therapy for HCV (sustained virologic response at week 12; SVR 12) also resulted in increase of the CD4+ lymphocytes level, which was considered as a positive effect of glecaprevir/pibrentasvir (p = 0.15). We observed significant differences in the level of liver enzymes (ALT and AST) (p = 0.01) between samples collected before antiviral therapy initiation and those collected during treatment, as well as 12 weeks after its completion (SVR12). All children demonstrated good tolerance of glecaprevir/pibrentasvir; none of them had adverse events, complaints, or clinical/laboratory changes. Conclusion. Thus, all children with HIV infection and CHC achieved SVR12 after the 8-week course of antiviral therapy with glecaprevir/pibrentasvir regardless of HCV genotype. Clinical manifestations (hepatosplenomegaly in 62.1%; asthenovegetative syndrome in 31.0%) were eliminated after 8 weeks of therapy. Laboratory manifestations (hepatic cytolysis (AST/ALT)) were normalized after 4 weeks of therapy. Antiviral treatment for HCV resulted in some increase in the level of CD4+ lymphocytes. We observed no adverse events caused by glecaprevir/pibrentasvir (neither clinical symptoms nor changes in complete blood count or liver function tests), which confirms the safety of this treatment regimen. Key words: antiretroviral therapy, HIV infection, children, direct-acting antivirals, chronic hepatitis C

Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1.

We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA) < 70 and 247 CSA ≥ 70 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes. Twenty-nine SNVs in 24 genes reaching P ≤ .002 and OR ≥ 1.5 comparing CSA < 70 to CSA ≥ 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (P < .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (P < .0001 and P < .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1β following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1β release. Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.

Delayed seroreversion of specifical antibody against HIV in HIV-exposed infants: A retrospective cohort study.

To investigate the seroreversion time in HIV-1-exposed but uninfected infants from two tertiary hospitals in China. This study retrospectively investigated the data of perinatal, HIV-1-exposed infants from hospitals in Beijing and Shenzhen. Maternal and infant medical records from both hospitals from January 2009 to December 2019 were reviewed, and the HIV antibody seroreversion times of infants were determined. From 2009 to 2019, a total of 485 HIV-1-exposed but uninfected infants were enrolled. The majority of infants were born at term with normal birth weight. The seroreversion rates were 89.3%, 94.2% and 100% at 12, 18 and 24months of age, respectively. There were no significant associations between seroreversion and several risk factors, such as gender, birth weight, gestational age, mode of delivery, postpartum prophylaxis and antiretroviral treatment duration. The mean value of HIV-specific immunoglobulin G concentration decreased from 15.4 at day 42 to 0.03 after 24months in HIV-exposed, uninfected infants. Clearance of HIV antibodies could take more than 18months in a small number of perinatally exposed infants. Caution should be used in excluding or diagnosing perinatal HIV infection in children with long persistence of HIV antibodies.

Pharmacokinetics and safety of early nevirapine-based antiretroviral therapy for neonates at high risk for perinatal HIV infection: a phase 1/2 proof of concept study

With increasing intention to treat HIV as early as possible, evidence to confirm the safety and therapeutic drug concentrations of a nevirapine-based antiretroviral regimen in the early neonatal period is needed. This study aims to establish dosing of nevirapine for very early treatment of HIV-exposed neonates at high risk of HIV acquisition. IMPAACT P1115 is a multinational phase 1/2 proof-of-concept study in which presumptive treatment for in-utero HIV infection is initiated within 48 h of birth in HIV-exposed neonates at high risk of HIV acquisition. Participants were neonates who were at least 34 weeks gestational age at birth and enrolled within 48 h of birth, born to women with presumed or confirmed HIV infection who had not received antiretrovirals during this pregnancy. The regimen consisted of two nucleoside reverse transcriptase inhibitors plus nevirapine dosed at 6 mg/kg twice daily for term neonates (≥37 weeks gestational age) or 4 mg/kg twice daily for 1 week and 6 mg/kg twice daily thereafter for preterm neonates (34 to <37 weeks gestational age). Here, we report the secondary outcomes of the study: nevirapine exposures in study weeks 1 and 2 and treatment-associated grade 3 or 4 adverse events at least possibly related to study treatment up to study week 4. A population pharmacokinetic model to assess nevirapine exposure was developed from dried blood spot and plasma nevirapine concentrations at study weeks 1 and 2. Nevirapine exposure was assessed in all patients with available blood samples and safety was assessed in all participants. This trial is registered at ClinicalTrials.gov (NCT02140255). Between Jan 23, 2015, and Sept 4, 2017, 438 neonates were enrolled and included in analyses; 36 had in-utero HIV infection and 389 (89%) were born at term. Neonates without confirmed in-utero HIV infection received nevirapine for a median of 13 days (IQR 7-14). Measured dried blood spot nevirapine concentrations were higher than the minimum HIV treatment target (3 μg/mL) in 314 (90%, 95% CI 86-93) of 349 neonates at week 1 and 174 (87%, 81-91) of 201 at week 2. In Monte-Carlo simulations, week 1 nevirapine concentrations exceeded 3 μg/mL in 80% of term neonates and 82% of preterm neonates. DAIDS grade 3 or 4 adverse events at least possibly related to antiretrovirals occurred in 30 (7%, 95% CI 5-10) of 438 infants but did not lead to nevirapine cessation in any neonates; neutropenia (25 [6%] neonates) and anaemia (six [1%]) were most common. Nevirapine at the dose studied was confirmed to be safe and provides therapeutic exposure concentrations. These data support nevirapine as a component of presumptive HIV treatment in high-risk neonates. National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Аnalysis of the epidemiological situation and perinatal HIV infection in the Vologda region

Purpose. To analyze the epidemiological situation and perinatal HIV infection in the Vologda region.Materials and methods. The article provides a retrospective and prospective analysis of data obtained from the forms of state statistical observation and accounting forms of medical documentation, using the Chi-square calculator, Fisher criterion, risk ratio to assess the effectiveness of measures to prevent perinatal HIV transmission in the Vologda region.The results of the study showed that the detection of HIV infection during pregnancy in the Vologda region tends to increase. At the same time, there are still problems such as adherence to dispensary monitoring and treatment in women who have drug dependence, which requires further improvement of the legal framework and clear implementation of approved algorithms by medical professionals.