Search

: Introduction: Limited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration. Methods: Patient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework. Results: Of the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm[sup.3] in SSA to 828 cells/mm[sup.3] in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was Conclusions: Children switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children., Introduction In 2018, there were an estimated 1.7 million children living with HIV globally and 160,000 new paediatric infections [1]. With the recommendation for immediate antiretroviral therapy (ART) [2], substantial [...]

: Introduction: The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk‐benefit messaging when a safety signal is identified. Discussion: The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll‐out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high‐quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. Conclusions: The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk‐benefit trade‐offs in a variety of contexts; guidance to transform this risk‐benefit balance into effective and agreed‐upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise., Abbreviations Introduction While there is an urgency to bring newer and more potent antiretroviral drugs developed in resource‐rich settings to resource‐limited settings as quickly as possible, evaluation of the safety [...]

Background Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%–40% of vertically acquired HCV infections clear spontaneously within 4–5 years. Methods Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA–negative infants in whom RNA was not detectable until after 6 weeks. Results Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1–81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1–18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0–76.9), 39.7% (CrI, 17.9–65.9), and 20.9% (CrI, 4.6–44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. Conclusions Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment. [ABSTRACT FROM AUTHOR]

Evidence suggests children HIV‐exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV‐exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother‐to‐Child HIV Transmission Programme after Option B+ implementation (2014–2018). Anthropometry was measured at enrolment (age 1–6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight‐for‐age (WAZ) and length‐for‐age (LAZ) z‐scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi‐variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82–6.17]), which was modified by co‐trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi‐faceted health risks, alongside maternal ART prescription, and follow‐up of mother‐child pairs. Key messages: Understanding the health risks of children HIV‐exposed and uninfected (CHEU) and the impact on their growth is of paramount importance for optimizing their health.This is one of the first studies examining correlates of CHEU growth since the implementation of Option B+ and uses a random subsample of a nationally representative cohort of women with HIV and CHEU in Malawi.Factors associated with stunting included infant low birthweight, optimal feeding, co‐trimoxazole prophylaxis, and maternal employment.Interventions targeting modifiable risk factors, alongside maternal antiretroviral therapy, and improved nutritional follow‐up of CHEU will contribute to improving CHEU growth in Malawi. [ABSTRACT FROM AUTHOR]

Around 0.4% of pregnant women in England have chronic hepatitis B virus (HBV) infection and need services to prevent vertical transmission. In this national audit, sociodemographic, clinical and laboratory information was requested from all maternity units in England for hepatitis B surface antigen-positive women initiating antenatal care in 2014. We describe these women's characteristics and indicators of access to/uptake of healthcare. Of 2542 pregnancies in 2538 women, median maternal age was 31 [IQR 27, 35] years, 94% (1986/2109) were non-UK born (25% (228/923) having arrived into the UK <2 years previously) and 32% (794/2473) had ⩾2 previous live births. In 39%, English levels were basic/less than basic. Antenatal care was initiated at median 11.3 [IQR 9.6, 14] gestation weeks, and 'late' (⩾20 weeks) in 10% (251/2491). In 70% (1783/2533) of pregnancies, HBV had been previously diagnosed and 11.8% (288/2450) had ⩾1 marker of higher infectivity. Missed specialist appointments were reported in 18% (426/2339). Late antenatal care and/or missed specialist appointments were more common in pregnancies among women lacking basic English, arriving in the UK ⩽2 years previously, newly HBV diagnosed, aged <25 years and/or with ⩾2 previous live births. We show overlapping groups of pregnant women with chronic HBV vulnerable to delayed or incomplete care. [ABSTRACT FROM AUTHOR]

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in 'real-life' settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5-5.2) years for the total cohort and 6.4 (3.6-8.0) years in Europe, 3.7 (2.0-5.4) years in North America, 2.5 (1.2-4.4) years in South and Southeast Asia, 5.0 (2.7-7.5) years in South America and the Caribbean, and 2.1 (0.9-3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3-2.1) years in North America to 7.1 (5.3-8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4-2.6) years in North America to 7.9 (6.0-9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%-2.8%), 15.6% (15.1%-16.0%), and 11.3% (10.9%-11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%-1.1%]) and highest in South America and the Caribbean (4.4% [3.1%-6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%-6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%-13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., Author(s): The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration, Amy L. Slogrove 1, Michael Schomaker 1, Mary-Ann Davies 1, Paige Williams 2, Suna Balkan 3, [...]

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 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 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 [less than or equal to]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., Author(s): The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord, Ali Judd 1,*, Elizabeth Chappell 1, Anna Turkova 1, Sophie Le Coeur 2,3, Antoni Noguera-Julian 4, [...]

Objective To investigate the scale-up of antenatal combination antiretroviral therapy (cART) in Ukraine since this became part of the national policy for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). Methods Data on 3535 HIV-positive pregnant women who were enrolled into the Ukraine European Collaborative Study in 2008-2010 were analysed. Factors associated with receipt of zidovudine monotherapy (AZTm)--rather than cART--and rates of mother-to-child transmission (MTCT) of HIV were investigated. Findings cART coverage increased significantly, from 22% of deliveries in 2008 to 61% of those in 2010. After adjusting for possible confounders, initiation of antenatal AZTm--rather than cART--was associated with cohabiting (versus being married; adjusted prevalence ratio, aPR: 1.09; 95% confidence interval, CI: 1.02-1.16), at least two previous live births (versus none; aPR: 1.22; 95% CI: 1.11-1.35) and a diagnosis of HIV infection during the first or second trimester (versus before pregnancy; aPR: 1.11; 95% CI: 1.03-1.20). The overall MTCT rate was 4.1% (95% CI: 3.4-4.9); 42% (49/116) of the transmissions were from the 8% (n = 238) of women without antenatal ART. Compared with AZTm, cART was associated with a 70% greater reduction in the risk of MTCT (adjusted odds ratio: 0.30; 95% CI: 0.16-0.56). Conclusion Between 2008 and 2010, access to antenatal cART improved substantially in Ukraine, but implementation of the World Health Organization's Option-B policy was slow. For MTCT to be eliminated in Ukraine, improvements in the retention of women in HIV care and further roll-out of Option B are urgently needed. Objective Etudier le renforcement du traitement prenatal par association d'antiretroviraux (TPAA) en Ukraine puisqu'il fait partie integrante de la politique nationale pour la prevention de la transmission mere-enfant (PTME) du virus de l'immunodeficience humaine (VIH). Methodes Une analyse a ete menee sur les donnees de 3535 femmes enceintes seropositives qui ont ete inscrites dans l'etude collaborative europeenne pour l'Ukraine en 2008-2010. Une etude a aussi ete realisee sur les facteurs associes a un traitement a la zidovudine en monotherapie (TZM), plutot qu'a un TPAA, et sur le taux de transmission de la mere a l'enfant (TME) du VIH. Resultats La part du TPAA a considerablement augmente, passant de 22% des traitements en 2008 a 61% en 2010. Apres ajustement pour les facteurs confondants possibles, le TZM prenatal, plutot que le TPAA, a ete associe au cas de cohabitation (par rapport au mariage; ratio de prevalence ajuste, RPa: 1,09; intervalle de confiance (IC) a 95%: 1,02 a 1,16), a au moins deux naissances anterieures (par rapport a aucune; RPa: 1,22; IC a 95%: 1,11 a 1,35) et a un diagnostic d'infection au VIH au cours du premier ou du deuxieme trimestre (par rapport a avant la grossesse; RPa: 1,11; IC a 95%: 1,03 a 1,20). Le taux de TME global etait de 4,1% (IC a 95%: 3,4 a 4,9), 42% (49/116) des transmissions provenaient des 8% (n = 238) de femmes n'ayant pas recu de TPAA. Par rapport au TZM, le TPAA a ete associe a une reduction superieure a 70% du risque de transmission mere-enfant (rapport des cotes ajuste, RCa: 0,3; IC a 95%: 0,16 a 0,56). Conclusion Entre 2008 et 2010, l'acces au TPAA s'est nettement ameliore en Ukraine, mais la mise en oeuvre de l'option B de la politique de l'Organisation mondiale de la Sante a ete lente. Pour que la TME soit eliminee en Ukraine, l'amelioration de la retention des femmes dans les services de soins du VIH et la poursuite du deploiement de l'option B sont des points urgents a regler. Objetivo Investigar la generalizacion del tratamiento antirretroviral combinado prenatal en Ucrania desde que entro a formar parte de la politica nacional de prevencion de la transmision de madre a hijo del virus de la inmunodeficiencia humana (VIH). Metodos Se analizaron los datos de 3535 mujeres embarazadas seropositivas incluidas en el Estudio Colaborativo Europeo Ucraniano entre 2008 y 2010. Se investigaron los factores asociados a la recepcion de una monoterapia con zidovudina--y no el tratamiento antirretroviral combinado prenatal--y las tasas de transmision de madre a hijo del VIH. Resultados La cobertura del tratamiento antirretroviral combinado prenatal aumento significativamente, del 22% de partos en 2008 al 61% de los de 2010. Tras ajustarla por los posibles factores de confusion, el inicio de la monoterapia con zidovudina--y no el tratamiento antirretroviral combinado prenatal--estuvo asociado con la cohabitacion (frente a los matrimonios; razon de prevalencia ajustada: 1,09; intervalo de confianza 95%: 1,02-1,16), al menos dos nacimientos vivos anteriores (frente a ninguno; razon de prevalencia ajustada: 1,22; intervalo de confianza 95%: 1,11-1,35) y un diagnostico de infeccion por VIH durante el primer o segundo trimestre (frente a antes del embarazo, razon de prevalencia ajustada: 1,11; intervalo de confianza 95%: 1,03-1,20). La tasa total de transmision de madre a hijo fue del 4,1% (intervalo de confianza 95% 3,4-4,9); el 42% (49/116) de las transmisiones fueron del 8% (n = 238) de las mujeres que no recibieron antirretrovirales prenatales. En comparacion con la monoterapia con zidovudina, el tratamiento antirretroviral combinado prenatal estuvo asociado con una reduccion un 70% mayor del riesgo de transmision (razon de posibilidades ajustada: 0,30; intervalo de confianza 95%: 0,16-0,56). Conclusion Entre 2008 y 2010, el acceso al tratamiento antirretroviral combinado prenatal mejoro sustancialmente en Ucrania, pero la implementacion del enfoque en la opcion B de la Organizacion Mundial de la Salud se revelo lenta. Para eliminar la transmision de madre a hijo en Ucrania, se necesitan con urgencia mejoras en la retencion de las mujeres en la atencion al VIH y un mayor despliegue de la opcion B., Introduction Among the countries of Europe, Ukraine has the highest prevalence of adult infection with human immunodeficiency virus (HIV) (1.6%) and the highest rate of mortality attributable to acquired immunodeficiency [...]