Universal antiretroviral therapy for HIV‐infected children: a review of the benefits and risks to consider during implementation

Barlow‐Mosha, Linda; Musiime, Victor; Davies, Mary‐Ann; Prendergast, Andrew J.; Musoke, Philippa; Siberry, George K.; Penazzato, Martina

doi:10.7448/ias.20.1.21552

Cited by 29 publications

(22 citation statements)

References 57 publications

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“…At database closure, 4% of children in care had still not initiated ART in 2016. As universal ART is scaling-up in accordance with 2017 WHO guidelines, there is an urgency to identify these children and initiate them on treatment as soon as possible [30].…”

Section: Discussionmentioning

confidence: 99%

Time‐varying age‐ and CD4‐stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium

Desmonde

Neilan

Musick

et al. 2020

J. Intern. AIDS Soc.

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Introduction: Evaluating outcomes of paediatric patients with HIV provides crucial data for clinicians and policymakers. We analysed mortality and clinical events rates among children, adolescents, and youth with perinatally acquired HIV (PHIV) aged 0 to 24 years stratified by time-varying age and CD4, before and after antiretroviral therapy (ART), in the paediatric IeDEA multiregional collaboration (East, West, Central and Southern Africa, Asia-Pacific, and Central/South America and the Caribbean). Methods: ART-na€ ıve children with HIV enrolled before age 10 (proxy for perinatal infection) at IeDEA sites between 2004 and 2016, with ≥1 CD4 measurement during follow-up were included. We estimated incidence rates (IR) and 95% confidence intervals (95% CI) of mortality and first occurrence of WHO-4 and WHO-3 events, excluding tuberculosis, during person-years (PY) spent within different age (<2, 2 to 4, 5 to 9, 10 to 14, 15 to 19, 20 to 24) and CD4 (percent when <5 years [<15%, 15% to 24%, ≥25%]; count when ≥5 years [<200, 200 to 499, ≥500 cells/µL]) strata. We used linear mixed models to predict CD4 evolution, with trends modelled by region. Results: In the pre-ART period, 49 137 participants contributed 51 966 PY of follow-up (median enrolment age: 3.9 years). The overall pre-ART IRs were 2.8/100 PY (95% CI: 2.7 to 2.9) for mortality, 3.3/100 PY (95% CI: 3.0 to 3.5) for first occurrence of a WHO-4 event, and 7.0/100 PY (95% CI: 6.7 to 7.4) for first occurrence of a WHO-3 event. Lower CD4 and younger age strata were associated with increased rates of both mortality and first occurrence of a clinical event. In the post-ART period, 52 147 PHIVY contributed 207 945 PY (ART initiation median age: 4.5 years). Overall mortality IR was 1.4/ 100 PY (95% CI: 1.4 to 1.5) and higher in low CD4 strata; patients at each end of the age spectrum (<2 and >19) had increased mortality post-ART. IRs for first occurrence of WHO-4 and WHO-3 events were 1.3/100 PY (95% CI: 1.2 to 1.4) and 2.1/100 PY (95% CI: 2.0 to 2.2) respectively. These were also associated with lower CD4 and younger age strata. Conclusions: Mortality and incidence of clinical events were highest in both younger (<2 years) and older (>19 years) youth with PHIV. Scaling-up services for <2 years (early access to HIV diagnosis and care) and >19 years (adolescent-and youth-focused health services) is critical to improve outcomes among PHIVY.

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Section: Discussionmentioning

confidence: 99%

Time‐varying age‐ and CD4‐stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium

Desmonde

Neilan

Musick

et al. 2020

J. Intern. AIDS Soc.

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“…Since the massive ART scale-up availability in low-income countries, the rate of vertical transmission of HIV-1 infection has considerably decreased along with the number of HIV-1-related pediatric deaths. ART administration has a positive impact on a variety of clinical symptoms associated with HIV-1 infection in children [ 1 ]. However, ART provided during the chronic phase of HIV-1 infection in children has ameliorated, but not reversed, abnormal features of immune activation [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Profiling of Inflammatory Proteins in Plasma of HIV-1-Infected Children Receiving Antiretroviral Therapy

et al. 2020

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Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-α, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.

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“…The specific pathways which result in impaired growth are multifactorial, including undernutrition, chronic inflammation, opportunistic infections, gastrointestinal illnesses, and endocrine abnormalities [4]. Previous clinical trials and observational studies have demonstrated improvements in growth after initiation of antiretroviral treatment (ART), although gains have often not been as strong in adolescents as among younger children.…”

Section: Introductionmentioning

confidence: 99%

Growth and pubertal development in HIV-infected adolescents

Williams

Jesson

2018

Current Opinion in HIV and AIDS

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Universal antiretroviral therapy for HIV‐infected children: a review of the benefits and risks to consider during implementation

Cited by 29 publications

References 57 publications

Time‐varying age‐ and CD4‐stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium

Time‐varying age‐ and CD4‐stratified rates of mortality and WHO stage 3 and stage 4 events in children, adolescents and youth 0 to 24 years living with perinatally acquired HIV, before and after antiretroviral therapy initiation in the paediatric IeDEA Global Cohort Consortium

Profiling of Inflammatory Proteins in Plasma of HIV-1-Infected Children Receiving Antiretroviral Therapy

Growth and pubertal development in HIV-infected adolescents

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