2018

29

Apr, 2019

Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study

 

Authors:Judd A, Chappell E, Turkova A; for European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.

Published in: PLoS Med. 2018;15(1): e1002491.

Background Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand.

Methods and Findings Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4–9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997–2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997–2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9–8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.

Conclusions In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

25

Mar, 2019

Migrant women living with HIV in Europe: are they facing inequalities in the prevention of mother-to-child-transmission of HIV?: The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord

 

Authors: Favarato G, Bailey H, Burns F, et al.

Published in: Eur J Public Health. 2018;28(1):55-60.

Background In pregnancy early interventions are recommended for prevention of mother-to-child-transmission (PMTCT) of HIV. We examined whether pregnant women who live with HIV in Europe and are migrants encounter barriers in accessing HIV testing and care.
Methods Four cohorts within the European Pregnancy and Paediatric HIV Cohort Collaboration provided data for pooled analysis of 11 795 pregnant women who delivered in 2002–12 across ten European countries. We defined a migrant as a woman delivering in a country different from her country of birth and grouped the countries into seven world regions. We compared three suboptimal PMTCT interventions (HIV diagnosis in late pregnancy in women undiagnosed at conception, late anti-retroviral therapy (ART) start in women diagnosed but untreated at conception and detectable viral load (VL) at delivery in women on antenatal ART) in native and migrant women using multivariable logistic regression models.
Results Data included 9421 (79.9%) migrant women, mainly from sub-Saharan Africa (SSA); 4134 migrant women were diagnosed in the current pregnancy, often (48.6%) presenting with CD4 count <350 cells/µl. Being a migrant was associated with HIV diagnosis in late pregnancy [OR for SSA vs. native women, 2.12 (95% CI 1.67, 2.69)] but not with late ART start if diagnosed but not on ART at conception, or with detectable VL at delivery once on ART.
Conclusions Migrant women were more likely to be diagnosed in late pregnancy but once on ART virological response was good. Good access to antenatal care enables the implementation of PMTCT protocols and optimises both maternal and children health outcomes generally.

 

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25

Mar, 2019

Time to switch to second-line antiretroviral therapy in children with HIV in Europe and Thailand

 

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.

Published in: Clin Infect Dis. 2018;66(4):594-603.

Background Global data on durability of first-line antiretroviral therapy (ART) in children with HIV is limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.

Methods Children <18-years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitor (NRTI) plus non-NRTI (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 3,668 children included, median [IQR] age at ART initiation was 6.1 [1.7,10.5] years. Initial regimens were 32% PI, 34% nevirapine (NVP), 33% efavirenz-based. Median duration of follow-up from ART start was 5.4 [2.9,8.3] years. Cumulative incidence of switch at 5 years was 21% (95% CI 20, 23), with lowest incidence in Russia/Ukraine and highest in UK/Ireland. Median time to switch was 30 [15, 58] months, two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load at ART start, and NVP-based initial regimens were associated with increased risk of switch. Among those switched, 65% had viral load <400c/mL at 12-months after start of second-line ART.

Conclusions One in five children switched to second-line 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.

 

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