Immunology of pediatric HIV infection

Tobin, Nicole H.; Aldrovandi, Grace M.

doi:10.1111/imr.12074

Cited by 101 publications

(123 citation statements)

References 373 publications

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“…Children experience more rapid HIV disease progression than adults, making them highly susceptible to opportunistic infections 5. Antiretroviral therapy (ART) can restore immune function and has enormously reduced morbidity and mortality among HIV-infected children.…”

Section: Introductionmentioning

confidence: 99%

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

Dodd¹,

Prendergast

Beecroft

et al. 2017

Thorax

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BackgroundChildren (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB incidence.ObjectivesDetermine the impact of HIV infection and ART on risk of incident TB disease in children.MethodsWe searched MEDLINE and Embase for studies measuring HIV prevalence in paediatric TB cases (‘TB cohorts’) and paediatric HIV cohorts reporting TB incidence (‘HIV cohorts’). Study quality was assessed using the Newcastle-Ottawa tool. TB cohorts with controls were meta-analysed to determine the incidence rate ratio (IRR) for TB given HIV. HIV cohort data were meta-analysed to estimate the trend in log-IRR versus CD4%, relative incidence by immunological stage and ART-associated protection from TB.Results42 TB cohorts and 22 HIV cohorts were included. In the eight TB cohorts with controls, the IRR for TB was 7.9 (95% CI 4.5 to 13.7). HIV-infected children exhibited a reduction in IRR of 0.94 (95% credible interval: 0.83–1.07) per percentage point increase in CD4%. TB incidence was 5.0 (95% CI 4.0 to 6.0) times higher in children with severe compared with non-significant immunosuppression. TB incidence was lower in HIV-infected children on ART (HR: 0.30; 95% CI 0.21 to 0.39). Following initiation of ART, TB incidence declined rapidly over 12 months towards a HR of 0.10 (95% CI 0.04 to 0.25).ConclusionsHIV is a potent risk factor for paediatric TB, and ART is strongly protective. In HIV-infected children, early diagnosis and ART initiation reduces TB risk.Trial registration numberCRD42014014276.

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Section: Introductionmentioning

confidence: 99%

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

Dodd¹,

Prendergast

Beecroft

et al. 2017

Thorax

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“…Neurodevelopmental outcomes may also be affected by immunological parameters such as viral load and CD4 + and CD8 + T-cell counts, which are well-established biomarkers of the clinical stage of HIV disease [15–17]. Higher viral loads have been shown to negatively impact domains of child behavior including emotional control, task shifting and inhibition [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

Ruiseñor-Escudero

Familiar‐Lopez

Sikorskii

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective To identify the nutritional and immunological correlates of memory and neurocognitive development as measured by the Mullen Scales of Early Learning (MSEL) and by the Color Object Association Test (COAT) among children in Uganda. Design This analysis uses baseline data collected between 2008 and 2010 from 119 HIV-infected children ages 1–6 years participating in a randomized controlled trial of an interventional parenting program in Kayunga, Uganda. Methods Peripheral blood draws were performed to determine immunological biomarkers. Unadjusted and adjusted linear regression models were used to relate MSEL and COAT scores to sociodemographic characteristics, weight-for-age Z-scores (WAZ), antiretroviral therapy (ART) status and immunological biomarkers. Results 111 children were included in the final analysis. Lower levels of CD4+ CD38+ T-cells (p=0.04) were associated to higher Immediate and Total Recall scores (p=0.04). Higher levels of CD8+ HLA-DR+ T-cells were associated with higher Total Recall score (p=0.04) of the COAT. Higher CD4+ CD38+ HLA-DR+ T-cells levels were associated with higher Gross Motor scores of the MSEL (p=0.02). WAZ was positively correlated to Visual Reception, Fine Motor, Expressive Language and composite score of the MSEL. Conclusions Overall, WAZ was a stronger predictor of neurocognitive outcomes assessed by the MSEL. CD4+ CD38+ T-cells were more specifically associated with memory-related outcomes. Future research should include immunological markers and standardized neurocognitive tests to further understand this relationship.

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“…A high plasma HIV-1 RNA level is commonly seen in infancy (the median age of patients in the 5 to <10 kg baseline weight band was six months), which, together with immunological immaturity, makes virologic suppression in infants more difficult to achieve and results in longer times to reach undetectable levels [32,33]. …”

Section: Discussionmentioning

confidence: 99%

PRINCE‐1: safety and efficacy of atazanavir powder and ritonavir liquid in HIV‐1‐infected antiretroviral‐naïve and ‐experienced infants and children aged ≥3 months to <6 years

Strehlau¹,

Donati

Arce

et al. 2015

Journal of the International AIDS Society

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IntroductionPRINCE-1 is an ongoing prospective, international, multicentre, nonrandomized, two-stage clinical trial assessing safety and efficacy of once-daily atazanavir (ATV) powder boosted with ritonavir (RTV) liquid plus optimized dual nucleoside reverse-transcriptase inhibitor (NRTI) background therapy in antiretroviral (ARV)-naïve and -experienced children with HIV-1 infection aged ≥3 months to <6 years.MethodsChildren with HIV-1 infection without prior ATV exposure and with a screening HIV-1 RNA ≥1000 copies/mL were enrolled. The dosing of ATV powder, boosted with 80 mg RTV liquid, was based on three baseline weight bands (5 to <10 kg=150 mg, 10 to <15 kg=200 mg and 15 to <25 kg=250 mg).ResultsOf the 56 treated patients, 46 completed 48 weeks of therapy, 67.9% were from Africa and 60.7% were ART-naïve. Median ages at baseline were 6, 35 and 55 months, and proportions with HIV-1 RNA >100,000 were 85.7, 52.6 and 25% in the three baseline weight bands, respectively. No unexpected safety events occurred and no deaths were reported. Over 48 weeks, upper respiratory tract infections, diarrhoea, vomiting and Grade 3 to 4 hyperbilirubinaemia occurred in 35.7, 35.7, 28.6, and 9.4% of patients, respectively; five patients (8.9%) discontinued due to adverse events (AEs); and 11 patients (19.6%) experienced serious adverse events. At Week 48, using a modified intent-to-treat analysis (two patients were excluded because they switched to ATV capsules before Week 48), 61.1 and 74.1% of patients overall had an HIV-1 RNA level <50 copies/mL and <400 copies/mL, respectively. Virologic suppression rates increased across the lowest to highest baseline weight bands (47.6, 68.4 and 71.4% had HIV-1 RNA <50 copies/mL, and 66.7, 73.7 and 85.7% had HIV-RNA <400 copies/mL, respectively) but did not differ meaningfully between ARV-naïve and -experienced patients. Overall, the median change from baseline in CD4 cell count was +363 cells/mm3, and the median change from baseline in CD4 percent was +7.5%.ConclusionsATV powder boosted with RTV liquid once daily plus optimized dual NRTI background therapy was effective and well tolerated in this ART-naïve or -experienced paediatric population aged ≥3 months to <6 years. No unexpected safety findings compared with those from previous ATV paediatric and adult studies were identified.

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Immunology of pediatric HIV infection

Cited by 101 publications

References 373 publications

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis

Nutritional and Immunological Correlates of Memory and Neurocognitive Development Among HIV-Infected Children Living in Kayunga, Uganda

PRINCE‐1: safety and efficacy of atazanavir powder and ritonavir liquid in HIV‐1‐infected antiretroviral‐naïve and ‐experienced infants and children aged ≥3 months to <6 years

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