Children living with HIV: a narrative review of recent advances in pediatric HIV research and their implications for clinical practice

Nalwanga, Damalie; Musiime, Victor

doi:10.1177/20499361221077544

Cited by 7 publications

(3 citation statements)

References 25 publications

(31 reference statements)

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“…Immunotherapy in the field of HIV aims to build HIV-specific immunity, rescue immune exhaustion, target latent reservoir eradication, and prevent or control viral rebound [67] upon ART cessation. In addition to early ART, immune-based HIV cure strategies also include T-cell, antibody-based, cytokine, and immune checkpoint blockade therapies in people with HIV (mostly adults) [68][69][70][71]. In CLWH and HIV-exposed uninfected (HEU) children, the main immunotherapeutic approaches that have been pursued include vaccines and bNAbs.…”

Section: State Of Current Immunotherapy Approaches In Childrenmentioning

confidence: 99%

Pediatric immunotherapy and HIV control

Chinunga,

Chahroudi,

Ribeiro

2024

Current Opinion in HIV and AIDS

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Purpose of review Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies. Recent findings During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials. Summary Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.

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Section: State Of Current Immunotherapy Approaches In Childrenmentioning

confidence: 99%

Pediatric immunotherapy and HIV control

Chinunga,

Chahroudi,

Ribeiro

2024

Current Opinion in HIV and AIDS

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“…Globally, there are 1.8 million children living with HIV (CLWH) and a reported 150,000 new HIV infections acquired every year through vertical transmission (in utero, childbirth, or breastfeeding). 1 African, Caribbean, and Black communities are among those most affected by the HIV pandemic. 2,3 This is observed both globally and in high-income countries like Canada, where populations of African ancestry are disproportionately represented among CLWH.…”

Section: Introductionmentioning

confidence: 99%

Lower neutrophil count without clinical consequence among children of African ancestry living with HIV in Canada

Bernard,

Ransy,

Brophy

et al. 2024

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective: To investigate the association between African ancestry and neutrophil counts among children living with HIV (CLWH). We also examined whether medications, clinical conditions, hospitalization, or HIV virologic control were associated with low neutrophil counts or African ancestry. Design: We conducted a secondary analysis of the Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) Study, a multicenter prospective cohort study of CLWH across eight Canadian pediatric HIV care centers. Methods: We classified CLWH according to African ancestry, defined as “African,” “Caribbean” or “Black” maternal race. Longitudinal laboratory data (white blood cells (WBCs), neutrophils, lymphocytes, viral load, CD4 count) and clinical data (hospitalizations, AIDS-defining conditions, treatments) were abstracted from medical records. Results: Among 217 CLWH (median age 14, 55% female), 145 were of African ancestry and 72 were of non-African ancestry. African ancestry was associated with lower neutrophil counts, WBC counts, and neutrophil-lymphocyte ratios. Neutrophil count<1.5×109/L was detected in 60% of CLWH of African ancestry, compared to 31% of CLWH of non-African ancestry (p<0.0001), representing a 2.0-fold higher relative frequency (95% CI 1.4-2.9). Neutrophil count was on average 0.74×109/L (95%CI 0.45-1.0) lower in CLWH of African ancestry (p<0.0001). Neither neutrophil count<1.5×109/L nor African ancestry was associated with medications, hospitalizations, AIDS-defining conditions, or markers of virologic control (viral load, sustained viral suppression, lifetime nadir CD4). Conclusion: In CLWH, African ancestry is associated with lower neutrophil counts, without clinical consequences. A flexible evaluation of neutrophil counts in CLWH of African ancestry may avoid unnecessary interventions.

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“…1 Much progress has been made in the field of paediatric antiretroviral treatment (ART), but major treatment gaps persist. 2 Lack of ageappropriate ART formulations that infants and children can easily swallow, have an acceptable taste and are easy to store remains the main obstacles to ART access. 3,4 Paediatric ART adherence levels vary from 49% to 100% in low-and middle-income countries (LMICs).…”

Section: Introductionmentioning

confidence: 99%

Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver–child dyads’ perspective

Rotsaert

Ogara

Mwanga-Amumpaire

et al. 2023

Therapeutic Advances in Infection

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Background: Worldwide, 1.7 million children younger than 15 years were living with HIV in 2021. Only 52% of them had access to antiretrovirals (ARVs). Lack of age-appropriate ARV formulations (i.e. easy to swallow for young infants, acceptable taste) remains the main obstacle to the access to ARVs. Therefore, a strawberry-flavoured Abacavir/Lamivudine/Lopinavir/Ritonavir (30/15/40/10 mg) fixed-dose combination of granules in a capsule (4-in-1) for children living with HIV weighing 3–25 kg was developed. Objective: We assessed caregivers’ perceived acceptability of the 4-in-1 compared with previous paediatric ARV formulations and factors influencing acceptability. Methods: This exploratory qualitative case study embedded in a phase I/II, open-label, randomized cross-over pharmacokinetic, safety and acceptability study (LOLIPOP) was conducted in three sites in Uganda (May 2019–October 2020). Thirty-six children weighing between 3 and 19.9 kg participated in the main study. We purposively sampled caregiver–child dyads according to weight bands, and conducted 20 semi-structured interviews with caregivers and 5 with healthcare providers. We triangulated these results with a quantitative acceptability questionnaire. We analysed interviews inductively using NVivo12 adopting a thematic analysis approach and acceptability questionnaires descriptively to assess concordance between them. Results: All caregivers found the 4-in-1 formulation highly acceptable and easier to use than previous formulations (i.e. pellets/tables/syrup). Appealing taste, ease of administration, easy storage and children’s acceptance contributed to acceptability despite structural challenges of food shortage and HIV stigma. Visible improvements in children’s health and comprehensive and tailored healthcare provider support to overcome initial difficulties such as vomiting increased caregivers’ acceptance. Concordant results from questionnaire- and interview-data confirmed high acceptability. Conclusion: Caregivers of children in all weight bands in this sample found the 4-in-1 granules highly acceptable compared with the pellets/tablets combination. Healthcare providers’ support to caregivers allowed for individual tailoring of drug administration despite challenges such as food shortage. This enabled short-term adherence. These findings informed further practical recommendations. Registration: Clinical trial number: NCT03836833

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Children living with HIV: a narrative review of recent advances in pediatric HIV research and their implications for clinical practice

Cited by 7 publications

References 25 publications

Pediatric immunotherapy and HIV control

Pediatric immunotherapy and HIV control

Lower neutrophil count without clinical consequence among children of African ancestry living with HIV in Canada

Acceptability of a new 4-in-1 Abacavir/Lamivudine/Lopinavir/Ritonavir paediatric fixed-dose combination: the caregiver–child dyads’ perspective

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