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Source publication
The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortal...
Contexts in source publication
Context 1
... Table 7 (see later) summarizes potential strategies for choosing second-line therapy. If the suggested options are not applicable, seek expert advice. ...
Context 2
... Table 7 summarizes potential strategies for choosing second-line therapy. If the suggested options are not applicable, seek expert advice. ...
Context 3
... studies in children will provide important information on the place of ETR and RPV in paediatric treatment strategies [IMPAACT P1090 (http:// clinicaltrials.gov/show/NCT01504841); IMPAACT P1111 (http://clinicaltrials.gov/show/NCT01975012)]. Table 7 summarizes potential strategies for choosing second-line therapy. ...
Citations
... In 2021, 160 000 children newly acquired HIV [1]. For these children, uninterrupted antiretroviral therapy (ART) is the mainstay of treatment [2][3][4] and has proven benefits, including delayed clinical progression to advanced disease [5,6] and reduction of HIV reservoir [7][8][9][10]. However, challenges faced with the daily administration of ART such as poor adherence, direct ART toxicities during critical periods of growth and development, and historically limited ART regimens for use in children have been well described as impediments to successful treatment [11,12]. ...
Purpose of review:
Treatment strategies for children with HIV are evolving, with considerations beyond plasma viremic control that raise the possibility of reducing or eliminating latent reservoirs to achieve posttreatment control. Novel strategies that maintain HIV viral suppression and allow time off small molecule antiretroviral therapy (ART) are of high priority. Trials with broadly neutralizing mAbs (bNAbs) have begun in children and may become a viable alternative treatment option. Recent bNAb treatment studies in adults indicate that bNAbs may be associated with a reduction in viral reservoirs, providing optimism that these agents may provide a pathway towards posttreatment control that rarely occurs with small molecule ART.
Recent findings:
Children with HIV provide an ideal opportunity to study bNAbs as an alternative treatment strategy that reduces direct ART toxicities during critical periods of growth and development, allows time off ART and takes advantage of the distinct features of the developing immune system in children that could facilitate induction of more potent autologous cellular and humoral immune responses against HIV-1. To date, paediatric bNAb studies with reported results include IMPAACT P1112, IMPAACT 2008, IMPAACT P1115 and the Tatelo study, and these results will be reviewed.
Summary:
In this review, we summarize the current and planned paediatric bNAb studies, with an emphasis on trial results available to date. We highlight the potential benefits of immune-based therapies for the maintenance of viral suppression and its potential for achieving viral remission in children living with HIV.
... Boosted-PI, most commonly including ritonavir-boosted lopinavir, and NNRTI-based regimens, including either efavirenz or nevirapine, were the most commonly prescribed regimens in PHIV in NL, consistent with the current guidelines for first-line ART regimens in children [22]. A ritonavir-boosted PI-based regimen is among the recommended preferred first-line ART in PHIV children, with ritonavir-boosted lopinavir recommended for children younger than six years old, ritonavir-boosted atazanavir for children 6-12 years old and ritonavirboosted atazanavir or ritonavir-boosted darunavir for children above twelve years old [22]. ...
... Boosted-PI, most commonly including ritonavir-boosted lopinavir, and NNRTI-based regimens, including either efavirenz or nevirapine, were the most commonly prescribed regimens in PHIV in NL, consistent with the current guidelines for first-line ART regimens in children [22]. A ritonavir-boosted PI-based regimen is among the recommended preferred first-line ART in PHIV children, with ritonavir-boosted lopinavir recommended for children younger than six years old, ritonavir-boosted atazanavir for children 6-12 years old and ritonavirboosted atazanavir or ritonavir-boosted darunavir for children above twelve years old [22]. In this study, we observed only a few prescriptions of atazanavir, potentially because of the concern of scleral icterus as a result of atazanavir-associated hyperbilirubinemia [23]. ...
Objectives:
To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status.
Design:
A prospective population-based open cohort including children with PHIV in NL.
Methods:
We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART).
Results:
We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups.
Conclusions:
Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes.
... INSTI-based regimens are nowadays considered the first choice in paediatric clinical guidelines. 36,37 Recently, a clinical trial showed that dolutegravir-based therapy was superior to the standard of care in children and adolescents as firstand second-line therapy. 38 Dolutegravir-based ART also presented an excellent profile leading to a high rate of virological suppression in a Spanish cohort of HIV-infected children and adolescents. ...
Objectives
The inadequacy of resistance monitoring in Latin America leads to circulation of HIV strains with drug resistance mutations (DRMs), compromising ART effectiveness. This study describes the DRM prevalence in HIV-infected paediatric patients in Panama.
Methods
During 2018–19, plasma was collected from 76 HIV-infected children/adolescents (5 ART-naive, 71 treated) in Panama for HIV-1 DRM pol analysis, predicted antiretroviral (ARV) susceptibility by Stanford, and HIV-1 variant phylogenetic characterization.
Results
HIV-1 pol sequences were recovered from 67 (88.2%) of 76 children/adolescents (median age 12 years), carrying 65 subtype B, 1 subtype G and 1 unique recombinant URF_A1B. Five were ART-naive and 62 ART-treated under virological failure (viraemia >50 copies/mL) with previous exposure to NRTIs, (100%), NNRTIs (45.2%), PIs (95.2%) and integrase strand transfer inhibitors (INSTIs, 17.7%). Among the treated patients, 34 (54.8%) carried resistant strains, with major DRMs to one (40.3%), two (9.7%) or three (4.8%) ARV families. Most of them harboured DRMs to NRTIs (58.5%) or NNRTIs (39%), but also major DRMs to PIs (4.9%) and INSTIs (6.5%). We also found dual-class NRTI + NNRTI (12.2%) and NNRTI + PI (2.6%) resistance. Two naive subjects carried viruses with DRMs to NRTIs and NRTI + NNRTI, respectively. Sequenced viruses presented high/intermediate resistance mainly to emtricitabine/lamivudine (48.9% each) and efavirenz/nevirapine (33.3% each). Most participants were susceptible to PIs (91.3%) and INSTIs (88.1%).
Conclusions
The high DRM prevalence to NRTIs and NNRTIs observed among treated HIV-infected children/adolescents in Panama justifies the need for routine resistance monitoring for optimal rescue therapy selection in this vulnerable population.
... Approval was extended to children ≥2 years weighing ≥10 kg in the USA in 2018 [5] and in Europe in 2020 [4]. ETR is included as a potential component of second and subsequent line regimens in previous and current international paediatric HIV treatment guidelines [6][7][8]. ...
Background
Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand.
Methods
Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit.
Results
177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm ³ , 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months ( n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start ( n=83) was 147 [16, 267] cells/mm ³ . Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens–Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation.
Conclusion
Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.
... Pulmonary tuberculosis is common opportunistic infectious diseases in AIDS patients, which enable to patients, obtain dual infections of AIDS and pulmonary tuberculosis [1]. The incidence of HIV-TB patients is 30 times than normal population [2], and the risk of death is 2.87 times than ordinary tuberculosis patients [3]. CD4 + T are command center of immune system, and T helper cell (Th17) and T regulatory cell (Treg) are a subset of CD4 + T cells. ...
Background: To ensure that patients with Acquired Immunodeficiency Syndrome (HIV) and active tuberculosis(TB) co-infection (HIV-TB) can get timely treatment, we investigated T helper cells17 (Th17), Tregulatorycells(Treg) levels in the peripheral blood mononuclear cells (PBMCs) of the TB, HIV, HIVTB patients provide a better consult for prediction of HIV-TB patients. Methods: A total of 62 patients with TB, HIV, HIV-TB and 30 healthy peoples were included in our study. The PBMCs were isolated from the peripheral blood and the level of Th17 and Treg cells were tested by flow cytometry. Serum levels of cytokines Interleukin 17 (IL-17), Interleukin 6 (IL-6) and Interleukin 10 (IL-10) were determined by ELISA. Results: Th17/Treg imbalance in HIV-TB patients, and is lower than HIV, TB and control group (Th17/Treg: 0.10±0.03 vs 0.25±0.08 vs 0.47±0.14 or 1.03±0.47, p<0.05). The expression of IL-10 in HIV-TB patients were significantly increased than HIV, T Band control groups, IL-17 and IL-6 were significantly decased (IL-10: 28.8±4.3 vs 23.6±3.6 vs 18.5±2.9 or 14.3±1.8pg/mL, p<0.05; IL- 17: 17.1±3.6 vs 24.2±4.2 vs 28.3±5.8 or 40.9±6.8pg/mL, p<0.05; IL-6: 15.9±2.1 vs 23.8±3.4 vs 27.8±4.3 or 32.5±4.6pg/mL, p<0.05). Conclusions: These studies revealed that Th17/Treg in HIV-TB patients was imbalanced, and suppressor T cell subsets are dominant, thus participate in immune pathogenesis of HIV-TB.
... Results: Out of the 1,085 records screened, we included five studies (one comparative cohort, three single phase 2-3 trial arms, one retrospective cohort) reporting 975 children and adolescents, of whom 56% (544) received atazanavir. Three studies reported all-cause treatment discontinuation rates, yielding a pooled incidence of 19% [15][16][17][18][19][20][21][22] at 12 months. The comparative cohort compared atazanavir to darunavir, with few grade 3-4 adverse events, except transient hyperbilirubinemia, occurring in half (92/188) of the atazanavir patients. ...
Background
Atazanavir/ritonavir is recommended as a preferred second-line antiretroviral regimen in children older than 3 months, alternatively to lopinavir/ritonavir. We performed a systematic review to assess safety and effectiveness of atazanavir use in children and adolescents.
Methods
We searched observational studies and clinical trials on Web of Science, Embase and Cochrane CENTRAL database between 2009/01/01 and 2020/10/01; as well as grey literature. We extracted safety (adverse events, grade 3 or 4 adverse events, treatment discontinuation) and effectiveness (CD4 cell counts and HIV viral load) outcomes. We estimated weighted summary pooled incidence with corresponding 95% confidence intervals.
Results
Out of the 1,085 records screened, we included five studies (one comparative cohort, three single phase 2-3 trial arms, one retrospective cohort) reporting 975 children and adolescents, of whom 56% (544) received atazanavir. Three studies reported all-cause treatment discontinuation rates, yielding a pooled incidence of 19% [15–22] at 12 months. The comparative cohort compared atazanavir to darunavir, with few grade 3–4 adverse events, except transient hyperbilirubinemia, occurring in half (92/188) of the atazanavir patients. No death occurred (two studies reporting). Four studies described increased CD4 cell counts and decreased HIV viral load at 6 or 12 months.
Conclusion
Few safety and effectiveness data were available for children and adolescents exposed to atazanavir. Transient grade 3–4 hyperbilirubinemia was the main adverse outcome reported. Immune and viral responses were descriptive. The use of atazanavir/ritonavir in children and adolescents needs further investigation, but remains a suitable option for a preferred second-line antiretroviral regimen.
PROSPERO number
CRD42022309230
... The actual risk of cardiovascular outcomes in young people living with perinatal HIV (PHIV), who (with ART) are surviving well into their thirties and forties, is still unclear. Therefore, the early and regular assessment of cardiovascular risk, due to HIV, ART and the increasing prevalence of traditional risk factors such as hypertension and obesity in adolescents, becomes increasingly important in the care and management of these young people (8). ...
... Longitudinal studies are becoming increasingly important to understand how the risk of chronic conditions change as PHIV age and change their behavior, and in particular as they transition into adult care. As recommended in current guidelines, a detailed history of cardiovascular risk factors, regular blood pressure and anthropometric measurements, as well as blood glucose levels and lipid panels should become a standard of care (8,29). However, the optimal management of traditional risk factors remains unclear, with variation in guidelines for thresholds for pharmacological intervention such a lipid lowering agents and antihypertensives in the general youth population (17). ...
Background
Antiretroviral therapy (ART) has increased life expectancy and consequently the risk of cardiovascular disease (CVD) in adults living with HIV. We investigated the levels and predictors of arterial stiffness in young people (YP) living with perinatal HIV (PHIV) and HIV negative YP in the Adolescents and Adults Living with Perinatal HIV (AALPHI) study.
Methods
AALPHI was a prospective study evaluating the impact of HIV infection and exposure to ART on YP living with PHIV (aged 13–21 years) who had known their HIV status for at least 6 months, and HIV negative YP (aged 13–23 years) who either had a sibling, friend or parent living with HIV. Participants were enrolled from HIV clinics and community services in England. Two hundred and thirteen PHIV and 65 HIV negative YP (42% siblings of PHIV) had pulse wave velocity (PWV) measurements taken (Vicorder software) from the supra-sternal notch to the middle of the thigh cuff, at their second interview in the study between 2015 and 2017. Average PWV was calculated from the three closest readings (≥3 and ≤ 12 m/s) within 0.6 m/s of each other. Linear regression examined predictors of higher (worse) PWV, including age, sex, HIV status and height as a priori , ethnicity, born outside UK/Ireland, alcohol/nicotine/drug use, weight, waist-to-hip-ratio, mean arterial pressure (MAP), caffeine 2 h before PWV and nicotine on day of PWV. A separate PHIV model included CD4, viral load, years taking ART and ART regimen.
Findings
One hundred and twenty eight (60%) PHIV and 45 (69%) HIV negative YP were female ( p = 0.18), with median (IQR) age 18 (16, 20) and 18 (16, 21) years ( p = 0.48) respectively. Most PHIV were taking a combination of three ART drugs from two classes. There was a trend toward higher (worse) mean PWV in the PHIV group than the HIV negative group [unvariable analysis 6.15 (SD 0.83) m/s vs. 5.93 (0.70) m/s, respectively, unadjusted p = 0.058], which was statistically significant in the multivariable analysis [adjusted p (ap) = 0.020]. In multivariable analysis being male (ap = 0.002), older age (ap < 0.001), higher MAP (ap < 0.001) and nicotine use on day of measurement (ap = 0.001) were also predictors of higher PWV. The predictors were the same in the PHIV model.
Interpretation
By late adolescence PHIV had worse PWV in comparison to HIV negative peers, and traditional risk factors for CVD (higher arterial pressure, being male and older age) were associated with higher PWV values. Regular detailed monitoring of cardiovascular risk factors should become standard of care for every young person with PHIV worldwide.
... This is the most recommended antiviral (Table 5), and is given after the first 14 days of life, as supportive therapy to other human immunodeficiency virus (HIV) drugs [175]. It cannot be used in premature infants born before 42 weeks [152]. ...
Since the beginning in December 2019, the SARS-CoV-2 outbreak appeared to affect mostly the adult population, sparing the vast majority of children who only showed mild symptoms. The purpose of this investigation is to assess the status on the mechanisms that give children and infants this variation in epidemiology compared to the adult population and its impact on therapies and vaccines that are aimed towards them. A literature review, including in vitro studies, reviews, published guidelines and clinical trials was performed. Clinical trials concerned topics that allowed a descriptive synthesis to be produced. Four underlying mechanisms were found that may play a key role in providing COVID-19 protection in babies. No guidelines are available yet for therapy due to insufficient data; support therapy remains the most used. Only two vaccines are approved by the World Health Organization to be used in children from 12 years of age, and there are currently no efficacy or safety data for children below the age of 12 years. The COVID-19 clinical frame infection is milder in children and adolescents. This section of the population can act as vectors and reservoirs and play a key role in the transmission of the infection; therefore, vaccines are paramount. More evidence is required to guide safely the vaccination campaign.
... The most recommended antiviral is Lopinavir/Ritonavir. It is used after the first 14 days of life, as a support therapy to other drugs for the human immunodeficiency virus (HIV) [209]. ...
Background:
The SARS-CoV-2 pandemic has involved a severe increase of cases worldwide in a wide range of populations. The aim of the present investigation was to evaluate recent insights about COVID-19 infection in children, infants and pregnant subjects.
Methods:
a literature overview was performed including clinical trials, in vitro studies, reviews and published guidelines regarding the present paper topic. A descriptive synthesis was performed to evaluate recent insights and the effectiveness of therapies for SARS-CoV-2 infection in children, infants and pregnant subjects.
Results:
Insufficient data are available regarding the relationship between COVID-19 and the clinical risk of spontaneous abortion and premature foetus death. A decrease in the incidence of COVID-19 could be correlated to a minor expression of ACE2 in childrens' lungs. At present, a modulation of the dose-effect posology for children and infants is necessary.
Conclusions:
Pregnant vertical transmission has been hypothesised for SARS-CoV-2 infection. Vaccines are necessary to achieve mass immunity for children and also pregnant subjects.
... The guidelines of the World Health Organization (WHO) recommend the use of ART soon after the diagnosis of HIV, regardless of the CD4 count, so that treatment of the infection begins in the early stages of infection 2 . According to the European Pediatric Network for the Treatment of HIV, the preferred scheme of ART's initially used in children are two or three reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors [NRTI]), together with a protease inhibitor (PI) enhanced with ritonavir or non-NRTI (NNRTI) 3 . The initial treatment recommendation for HIV in children was updated by the WHO in 2019 4 , and the firstline recommendation for children and adolescents is a therapeutic regimen with dolutegravir (DTG) in combination with a NRTI. ...
The safety of using different antiretroviral therapies (ART) in pediatric HIV/AIDS patients is not well-established. Therefore, this study aimed to assess the safety of ART in children. A systematic review of randomized clinical trials (RCTs) was conducted to assess the safety of ART used by pediatric patients living with HIV/AIDS. The electronic search was conducted in PubMed and Scopus, in addition to a manual search. Studies were included if they assessed the safety of ART compared to placebo or another ART. Direct and indirect meta-analyses were conducted regarding safety outcomes. The systematic review included 21 RCTs. The studies included more than 5500 participants, and age ranged from 3 months to 18 years. The drugs evaluated were nucleoside reverse transcriptase inhibitors (NRTI); non-NRTI; and protease inhibitors. The predominant route of infection was vertical. Direct meta-analyses were performed for the outcomes sleep disorders, hepatobiliary disorders, respiratory disorders, hypertransaminasemia, neutropenia, hospitalization, and death. For these outcomes, no statistically significant differences were found. Indirect meta-analyses were performed for the outcomes anemia, gastrointestinal disorders, liver disorders, severe adverse events (AE), AE that led to changes in treatment, fever, and skin manifestations. However, no statistically significant differences were found for these outcomes. In this study, non-significant differences were detected in the safety of different ART used in pediatric individuals. The choice of appropriate therapy should be based on its efficacy and the individual characteristics of each patient.
