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Viruses
Special Issues
Pediatric HIV Infection and AIDS
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Pediatric HIV Infection and AIDS

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (14 December 2022) | Viewed by 20386

Special Issue Editors

Dr. Jason C. Brophy

E-Mail Website
Guest Editor
Department of Pediatrics, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Interests: epidemiology; pediatric/perinatal HIV; congenital CMV infection
Dr. Fatima Kakkar

E-Mail Website
Guest Editor
Département de pédiatrie, Université de Montréal, Montréal, QC H3T 1J4, Canada
Interests: Paediatric HIV; Feto-maternal infections; Epidemiology

Special Issue Information

Dear Colleagues,

While the world has been preoccupied with the SARS-CoV-2 pandemic this past year, the HIV epidemic continues on and remains a major global health concern, especially for children. Annually, an estimated 1.3 million children are exposed to HIV and antiretroviral therapy, and while new infections have thankfully decreased, there are concerns about the long-term health of children who are HIV exposed and uninfected (CHEU). Among the 1.8 million children living with HIV, only 53% are diagnosed and on treatment, compared to 68% of adults. As this population of children ages, questions remain on optimal ART choices and formulations, how to maintain life-long adherence, and the possibility of a functional cure.

In this Special Edition of Viruses, we welcome submissions that focus on pediatric HIV, with a look toward the future and how to optimize strategies for prevention, early diagnosis, treatment, and functional cure. We welcome manuscripts from all geographic regions which focus on:

  • Perinatal HIV prevention;
  • Early infant diagnosis;
  • Breastfeeding and risk of perinatal transmission;
  • Acute and long-term health issues among CHEU;
  • Optimizing pediatric antiretroviral therapy, from infancy to adolescence;
  • Pediatric HIV treatment monitoring and comorbidities;
  • Advances in pediatric cure therapies, reservoir assays;
  • Nonperinatal pediatric HIV: epidemiology, risk factors.

Dr. Jason C. Brophy
Dr. Fatima Kakkar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pediatric
  • perinatal
  • HIV
  • CHEU (children who are HIV exposed and uninfected)
  • cure
  • antiretroviral therapy
  • diagnosis, prevention, comorbidities

Published Papers (7 papers)

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Research

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14 pages, 1263 KiB  
Article
Early Childhood Growth Parameters in South African Children with Exposure to Maternal HIV Infection and Placental Insufficiency
by Mothusi Nyofane, Marinel Hoffman, Helen Mulol, Tanita Botha, Valerie Vannevel, Robert Pattinson and Ute Feucht
Viruses 2022, 14(12), 2745; https://doi.org/10.3390/v14122745 - 09 Dec 2022
Viewed by 1375
Abstract
Maternal HIV exposure and intrauterine growth restriction (IUGR) due to placental insufficiency both carry major risks to early child growth. We compared the growth outcomes of children aged 18 months who had abnormal umbilical artery resistance indices (UmA-RI), as a marker of placental [...] Read more.
Maternal HIV exposure and intrauterine growth restriction (IUGR) due to placental insufficiency both carry major risks to early child growth. We compared the growth outcomes of children aged 18 months who had abnormal umbilical artery resistance indices (UmA-RI), as a marker of placental insufficiency, with a comparator group of children with normal UmA-RI during pregnancy, as mediated by maternal HIV infection. The cross-sectional study included 271 children, grouped into four subgroups based on HIV exposure and history of normal/abnormal UmA-RI, using available pregnancy and birth information. Standard procedures were followed to collect anthropometric data, and z-scores computed as per World Health Organization growth standards. Lower length-for-age z-scores (LAZ) were observed in children who were HIV-exposed-uninfected (CHEU) (−0.71 ± 1.23; p = 0.004) and who had abnormal UmA-RI findings (−0.68 ± 1.53; p < 0.001). CHEU with abnormal UmA-RI had lower LAZ (−1.3 ± 1.3; p < 0.001) and weight-for-age z-scores (WAZ) (−0.64 ± 0.92; p = 0.014) compared to the control group. The prevalence of stunting was 40.0% in CHEU with abnormal UmA-RI and 16.0% in CHEU with normal UmA-RI (p < 0.001; p = 0.016, respectively). In conclusion, maternal HIV exposure and placental insufficiency are independent risk factors for childhood stunting, with this risk potentiated when these two risk factors overlap. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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12 pages, 1490 KiB  
Article
Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV
by Isabelle Bernard, Doris G. Ransy, Jason Brophy, Fatima Kakkar, Ari Bitnun, Lindy Samson, Stanley Read, Hugo Soudeyns, Michael T. Hawkes and EPIC4 Study Group
Viruses 2022, 14(12), 2602; https://doi.org/10.3390/v14122602 - 23 Nov 2022
Cited by 1 | Viewed by 1446
Abstract
Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, [...] Read more.
Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC4). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 μg/L (IQR 19–39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = −0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 μg/L (interquartile range, IQR 33–44) versus 24 μg/L (IQR 19–35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, p = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, p = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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13 pages, 1747 KiB  
Article
Sustained Virologic Suppression Reduces HIV-1 DNA Proviral Levels and HIV Antibodies in Perinatally HIV-Infected Children Followed from Birth
by Trevon Fuller, Tara Kerin, Ruth Cortado, Maria de Lourdes Benamor Teixeira, Maria Isabel Fragoso da Silveira Gouvêa, Christianne Moreira, Maria Leticia Santos Cruz, José Henrique Pilotto, Ivete Gomes, Breno Santos, Tauí Rocha, Priya R. Soni, Esau Joao, Myung Shin-Sim, Yvonne Bryson and Karin Nielsen-Saines
Viruses 2022, 14(11), 2350; https://doi.org/10.3390/v14112350 - 26 Oct 2022
Cited by 1 | Viewed by 1606
Abstract
The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA [...] Read more.
The extent to which perinatally HIV-infected children, following cART initiation, develop a low proviral reservoir burden over time, as measured by HIV DNA droplet-digital polymerase chain reaction (ddPCR) and the effect on HIV antibody is not well characterized. We measured proviral HIV DNA and plasma RNA virus load (VL) in 37 perinatally HIV-infected children at 6 months of age who initiated stable cART. At 6–11 years of age, HIV proviral DNA, HIV VL (RNA), and HIV antibody by Western Blot (WB) were assessed. CART was initiated before 6 months of age in 13 children and after 6 months in 24. At school age, the HIV DNA levels did not differ by the timing of cART, and the HIV DNA levels were lower in children with negative/indeterminate WB (p = 0.0256). Children with undetectable HIV RNA VL > 50% of the time since cART initiation had lower median DNA VL than children with undetectable VL < 50% of the time (p = 0.07). Long-term viral suppression in perinatally HIV-infected children is associated with a decrease in HIV antibodies and reduced HIV reservoirs. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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Review

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20 pages, 2936 KiB  
Review
Prevention of the Vertical Transmission of HIV; A Recap of the Journey so Far
by Maria Camila Cardenas, Sheila Farnan, Benjamin L. Hamel, Maria Camila Mejia Plazas, Elise Sintim-Aboagye, Dawn R. Littlefield, Supriya Behl, Sohan Punia, Elizabeth Ann L Enninga, Erica Johnson, Zelalem Temesgen, Regan Theiler, Clive M. Gray and Rana Chakraborty
Viruses 2023, 15(4), 849; https://doi.org/10.3390/v15040849 - 26 Mar 2023
Cited by 3 | Viewed by 7143
Abstract
In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset [...] Read more.
In 1989, one in four (25%) infants born to women living with HIV were infected; by the age of 2 years, there was 25% mortality among them due to HIV. These and other pieces of data prompted the development of interventions to offset vertical transmission, including the landmark Pediatric AIDS Clinical Trial Group Study (PACTG 076) in 1994. This study reported a 67.5% reduction in perinatal HIV transmission with prophylactic antenatal, intrapartum, and postnatal zidovudine. Numerous studies since then have provided compelling evidence to further optimize interventions, such that annual transmission rates of 0% are now reported by many health departments in the US and elimination has been validated in several countries around the world. Despite this success, the elimination of HIV’s vertical transmission on the global scale remains a work in progress, limited by socioeconomic factors such as the prohibitive cost of antiretrovirals. Here, we review some of the key trials underpinning the development of guidelines in the US as well as globally, and discuss the evidence through a historic lens. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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14 pages, 323 KiB  
Review
Immune and Metabolic Alterations in Children with Perinatal HIV Exposure
by Louise D. V. du Toit, Andrea Prinsloo, Helen C. Steel, Ute Feucht, Roan Louw and Theresa M. Rossouw
Viruses 2023, 15(2), 279; https://doi.org/10.3390/v15020279 - 18 Jan 2023
Cited by 2 | Viewed by 1792
Abstract
With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children [...] Read more.
With the global rollout of mother-to-child prevention programs for women living with HIV, vertical transmission has been all but eliminated in many countries. However, the number of children who are exposed in utero to HIV and antiretroviral therapy (ART) is ever-increasing. These children who are HIV-exposed-but-uninfected (CHEU) are now well recognized as having persistent health disparities compared to children who are HIV-unexposed–and-uninfected (CHUU). Differences reported between these two groups include immune dysfunction and higher levels of inflammation, cognitive and metabolic abnormalities, as well as increased morbidity and mortality in CHEU. The reasons for these disparities remain largely unknown. The present review focuses on a proposed link between immunometabolic aberrations and clinical pathologies observed in the rapidly expanding CHEU population. By drawing attention, firstly, to the significance of the immune and metabolic alterations observed in these children, and secondly, the impact of their healthcare requirements, particularly in low- and middle-income countries, this review aims to sensitize healthcare workers and policymakers about the long-term risks of in utero exposure to HIV and ART. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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Graphical abstract

25 pages, 1671 KiB  
Review
Advances in Pediatric HIV-1 Cure Therapies and Reservoir Assays
by Priya Khetan, Yufeng Liu, Adit Dhummakupt and Deborah Persaud
Viruses 2022, 14(12), 2608; https://doi.org/10.3390/v14122608 - 23 Nov 2022
Cited by 4 | Viewed by 2895
Abstract
Significant advances in the field of HIV-1 therapeutics to achieve antiretroviral treatment (ART)-free remission and cure for persons living with HIV-1 are being made with the advent of broadly neutralizing antibodies and very early ART in perinatal infection. The need for HIV-1 remission [...] Read more.
Significant advances in the field of HIV-1 therapeutics to achieve antiretroviral treatment (ART)-free remission and cure for persons living with HIV-1 are being made with the advent of broadly neutralizing antibodies and very early ART in perinatal infection. The need for HIV-1 remission and cure arises due to the inability of ART to eradicate the major reservoir for HIV-1 in resting memory CD4+ T cells (the latent reservoir), and the strict adherence to lifelong treatment. To measure the efficacy of these cure interventions on reservoir size and to dissect reservoir dynamics, assays that are sensitive and specific to intact proviruses are critical. In this review, we provided a broad overview of some of the key interventions underway to purge the reservoir in adults living with HIV-1 and ones under study in pediatric populations to reduce and control the latent reservoir, primarily focusing on very early treatment in combination with broadly neutralizing antibodies. We also summarized assays currently in use to measure HIV-1 reservoirs and their feasibility and considerations for studies in children. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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17 pages, 779 KiB  
Review
Immune Dysregulation Is Associated with Neurodevelopment and Neurocognitive Performance in HIV Pediatric Populations—A Scoping Review
by Monray E. Williams, Anicia Janse Van Rensburg, Du Toit Loots, Petrus J. W. Naudé and Shayne Mason
Viruses 2021, 13(12), 2543; https://doi.org/10.3390/v13122543 - 18 Dec 2021
Cited by 4 | Viewed by 2765
Abstract
HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric [...] Read more.
HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric populations are not well understood, we conducted a scoping review on this topic. The study aimed to systematically review the association of blood and cerebrospinal fluid (CSF) immune markers with neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Studies were selected based on a set eligibility criterion. Titles, abstracts, and full texts were assessed by two independent reviewers. Data from the selected studies were extracted and analyzed by two independent reviewers. Seven studies were considered eligible for use in this context, which included four cross-sectional and three longitudinal studies. An average of 130 (±70.61) children living with HIV, 138 (±65.37) children exposed to HIV but uninfected and 90 (±86.66) HIV-negative participants were included across the seven studies. Results indicate that blood and CSF immune markers are associated with neurocognitive development/performance in pediatric HIV populations. Only seven studies met the inclusion criteria, therefore, these limited the number of significant conclusions which could have been made by using such an approach. All considered, the evidence suggests that immune dysregulation, as in the case of adult HIV populations, also has a significant association with neurocognitive performance in pediatric HIV populations. Full article
(This article belongs to the Special Issue Pediatric HIV Infection and AIDS)
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