Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Maternal HIV-1 DNA load and mother-to-child transmission

While many factors contribute to mother-to-child transmission (MTCT) of HIV-1, maternal plasma HIV-1 RNA viral load (RNA-VL) has been consistently found as the main risk factor, including when antiretroviral prophylaxis was used to prevent MTCT. However the predictive value of RNA-VL is poor. A recent study of HIV-1-positive pregnant women who did not receive antiretroviral prophylaxis reported an association between HIV-1 DNA viral load (DNA-VL) and MTCT that was stronger than the association between RNA-VL and MTCT. We sought to determine if HIV-1 DNA-VL was independently associated with MTCT of HIV in a population of women who received zidovudine prophylaxis during pregnancy and whose infants received zidovudine after birth. Patients were 33 non-breastfeeding transmitting (TR) and 33 nontransmitting mothers (NTR) from Perinatal HIV Prevention Trial (PHPT-1), a multicenter clinical trial conducted in Thailand comparing zidovudine prophylaxis durations to prevent MTCT. TR and NTR mothers were matched according to baseline RNA-VL. Maternal peripheral blood mononuclear cell (PBMC)-associated HIV-1 DNA was extracted from whole blood, and DNA-VL was established by quantitative real-time polymerase chain reaction. We found that TR had a significantly higher cell-associated HIV-1 DNA viral load than did NTR. Median TR DNA-VL was 2.54 log(10) copies per microgram PBMC DNA, while it was 2.28 log(10) copies per microgram PBMC DNA in NTR (Wilcoxon p = 0.02). In summary, HIV-1 DNA viral load was associated with MTCT in a population of women who received antiretroviral prophylaxis during pregnancy, independently from RNA viral load

COVID‐19: Facemasks, healthcare policies and risk factors in the crucial initial months of a global pandemic

Previous pandemics have shown that facemask use becomes highly popular in public settings due to fear of the disease spreading. There is, however, a lack of strong scientific evidence that facemasks can significantly reduce the spread of respiratory diseases and as such, most governing policies do not mandate these coverings. There is a stark contrast between the policies and acceptance of facemasks across different geographies. In this work, several data sources have been thoroughly analysed to elucidate how viral diseases are transmitted and spread with particular emphasis on the novel SARS‐CoV‐2 virus which is causing an outbreak of COVID‐19. The different types of facemasks and respirators are also explained, the nature of their design and their efficacy is also examined. Several key factors which have been hypothesised to contribute to the spread of viral infections are elaborated in detail including the effect of temperature and humidity, public transportation systems, population density, socio‐economics and sociology. In this work, data are analysed to explain how the disease is spread, how facemasks function and the differences in the number of initial cases based on several contributing factors to the spread of disease. There are also some dangers in automatically recommending community facemask wearing, such as a reduction in the immune system functionality from the reduced exposure to microbes and the disposal issues which result from the large‐scale use of such materials. The questions of whether facemasks are useful in a community setting or if they divert valuable material away from critical healthcare providers are discussed

Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

International audienceIn human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders