EPPICC

26

Mar, 2019

Nucleoside reverse transcriptase inhibitor backbones and pregnancy outcomes

 

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

Published in: Aids. 2019;33(2):295-304.

Abstract:

ObjectivesThe aim of this study was to investigate whether specific nucleoside reverse transcriptase inhibitor (NRTI) backbones are associated with risk of adverse pregnancy outcomes among pregnant women starting antiretroviral therapy (ART).

DesignSeven observational studies across eight European countries of pregnancies in HIV-positive women.

MethodsIndividual-level data were pooled on singleton pregnancies conceived off-ART in which a single combination ART regimen was initiated at least 2 weeks before delivery, and ending in a live birth in 2008–2014. Preterm delivery (PTD) was defined as less than 37 gestational weeks and small-for-gestational-age (SGA) as less than 10th percentile according to INTERGROWTH standards. Poisson regression models were fitted to investigate associations between NRTI backbones and PTD/SGA.

ResultsOut of 7193 pregnancies, 45% (3207) were in UK/Ireland, 44% (3134) in Ukraine. 10% (722/7193) of deliveries were preterm and 11.1% (785/7089) of newborns SGA. The most common NRTI backbones were zidovudine (ZDV)-lamivudine (3TC) (71%), tenofovir (TDF)-XTC (16%) and abacavir (ABC)-3TC (10%) with TDF-containing backbone use increasing over time. Overall, 77% of regimens contained ritonavir-boosted lopinavir (LPV/r). There was no association between NRTI backbone and PTD in main adjusted analyses [adjusted prevalence ratios (aPRs) 0.97 (95% confidence interval, 95% CI 0.73–1.28] for ABC-3TC and aPR 1.06 (95% CI 0.83–1.35) for TDF-XTC, both vs. ZDV-3TC) or in 4720 pregnancies on LPV/r [aPR 1.03 (95% CI 0.74–1.43) for ABC-3TC and aPR 1.16 [0.85-1.57] for TDF-XTC, both vs. ZDV-3TC]. Infants exposed to ABC-3TC or TDF-XTC in utero were less likely to be SGA than those exposed to ZDV-3TC [aPR 0.72 (95% CI 0.53–0.97) and aPR 0.70 (95% CI 0.53–0.93), respectively].

ConclusionResults support the safety of TDF-XTC backbones initiated in pregnancy with respect to gestation length and birthweight.

26

Mar, 2019

Birth Defects After Exposure to Efavirenz-Based Antiretroviral Therapy at Conception/First Trimester of Pregnancy A Multicohort Analysis

 

Authors:Martinez de Tejada B; European Pregnancy and Paediatric HIV Cohort Collaboration Study Group.

Published in: J Acquir Immune Defic Syndr. 2019;80(3):316-324.

Abstract:

BackgroundTo investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects.

SettingSeven observational studies of pregnant HIV-positive women across 13 European countries and Thailand.

MethodsIndividual-level data were pooled on singleton pregnancies included in participating cohorts in 2002–2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects.

ResultsWe included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non–EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported.

ConclusionsPrevalence of birth defects after exposure to EFV-based compared with non–EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.

 

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.

Abstract:

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

Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

 

Authors:Chan MK, Goodall R, Judd A, et al.

Published in: Aids. 2019

Abstract:

Objective

To identify predictors of faster time to virological suppression among infants starting combination antiretroviral therapy (cART) early in infancy.

Design

Cohort study of infants from Europe and Thailand included in studies participating in the European Pregnancy and Paediatric HIVCohort Collaboration (EPPICC).

Methods

Infants with perinatal HIV starting cART aged <6 months with ≥1 viral load (VL) measurement within 15 months of cART initiation were included. Multivariable interval-censored flexible parametric proportional hazards models were used to assess predictors of fastervirological suppression, with timing of suppression assumed to lie in the interval between last VL≥400 and first VL<400copies/ml.

Results

Of 420 infants, 59% were female and 56% from Central/Western Europe, 26% UK/Ireland, 15% Eastern Europe and 3% Thailand; 46% and 54% started a boosted protease inhibitor- or non-nucleoside reverse transcriptase inhibitor- based regimen, respectively. At cART initiation, the median age, CD4% and VL were 2.9 (IQR:1.4-4.1) months, 34 (IQR:24-45)% and 5.5 (IQR:4.5-6.0) log10copies/ml, respectively. Overall, an estimated 89% (95%CI:86-92%) achieved virological suppression within 12 months of cART start. In multivariable analysis, younger age (aHR:0.84 per month older; P < 0.001), higher CD4% (aHR:1.11 per 10% higher; P = 0.010) and lower log10 VL (aHR:0.85 per log10 higher; P < 0.001) at cART initiation independently predicted faster virological suppression.

Conclusion

We observed a significant independent effect of age at cART initiation, even within a narrow 6 months window from birth. These findings support the earliest feasible cART initiation in infants and suggest that early therapy influences key virological and immunological parameters that could have important consequences for long term health.This is an open access article distributed under the Creative Commons Attribution License 4.0, (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

 

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.

Abstract:

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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27

Dec, 2016

Safety of zidovudine/lamivudine scored tablets in children with HIV infection in Europe and Thailand.

 

Published in: European Journal of Clinical Pharmacology, in press.

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20

Nov, 2016

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study

 

Authors: Turkova A, Chappell E, Chalermpantmetagul S, et al.

Published in: Int J Tuberc Lung Dis 2016, 20:1448-1456.

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11

Nov, 2016

Interventions to improve treatment, retention and survival outcomes for adolescents with perinatal HIV-1 in high- and middle-income countries: Moving on up.

 

Authors: Judd A, Sohn A, Collins J.

Published in: Current Opinion in HIV and AIDS 2016; 11(5): 477-486

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8

Nov, 2016

Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children – a EuroCoord-CHAIN-EPPICC joint project.

 

Published in: BMC Infectious Diseases, in press.

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14

Sep, 2016

Higher rates of triple class virologic failure in perinatally HIV-infected teenagers compared to heterosexually infected young adults in Europe. 

 

Authors: Judd A, Lodwick R, Noguera-Julian A, Gibb DM, Butler K, Costagliola D, Sabin C, van Sighem A, Ledergerber B, Torti C, Mocroft A, Podzamczer D, Dorrucci M, De Wit S, Obel N, Dabis F, Cozzi-Lepri A, García F, Brockmeyer NH, Warszawski J, Gonzalez-Tome MI, Mussini C, Touloumi G, Zangerle R, Ghosn J, Castagna A, Fätkenheuer G, Stephan C, Meyer L, Campbell MA, Chene G, Phillips A; Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord.

Published in: HIV Medicine, in press.

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