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

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

Is the interruption of antiretroviral treatment during pregnancy an additional major risk factor for mother-to-child transmission of HIV type 1?

BACKGROUND: There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission.METHODS: Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART.RESULTS: Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range [IQR], 5-6 weeks) and the time without treatment was 8 weeks (IQR, 7-11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23-36 weeks) and the time without treatment was 6 weeks (IQR, 2-9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval [CI], 0.7%-2.3%), whereas it was 4.9% (95% CI, 1.9%-13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%-72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery >4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission.CONCLUSIONS: Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health

Children living with HIV in Europe: do migrants have worse treatment outcomes?

Objectives: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. Methods: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models. Results: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409). However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96–2.38, p = 0.072). Conclusions: After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring