Suchergebnisse

IntroductionIn the United Kingdom and Ireland more than 40% of individuals living with perinatally acquired HIV are now aged >16. Globally, increasing numbers of women with perinatally acquired HIV are becoming pregnant, but data on fertility and pregnancy outcomes is scarce. We present pregnancy outcome data for this emerging cohort.MethodsPregnancies in diagnosed HIV‐infected women in the United Kingdom and Ireland, and children diagnosed with HIV, are reported to the National Study of HIV in Pregnancy and Childhood. We analyzed data on pregnancies in women diagnosed aged ≤13 with perinatally acquired HIV, reported by June 2014.ResultsA total of 759 females born before 2001, diagnosed with perinatally acquired HIV aged ≤13 years, and in care in the UK and Ireland have been reported. Forty‐four of these (6%) have had at least one pregnancy reported, with nineteen 2nd and four 3rd/4th pregnancies. Women's year of birth ranged from 1985 to 1996; 60% of women were UK/Irish‐born and 39% African‐born. Twenty one percent were diagnosed at <2 years, 39% at 2–7 and 41% at 8–13 years. Nine pregnancies were conceived in 2005–07, 22 in 2008–10 and 36 in 2011–13. Median age at conception of first pregnancy was 19 years. CD4 count was >500 cells/µL in 36% of first pregnancies, 350–499 in 15% and <350 in 49%. Women were on antiretroviral therapy (ART) at conception in 71% of pregnancies. There were 51 singleton live births, 2 miscarriages, 9 terminations and 5 continuing to term. In 17 live births to women not on ART at conception, median gestational age at start of ART was 17 weeks (range 3–29). HIV viral load was <50 copies/mL near delivery in 64% of live births, 51–1000 in 31% and >1000 in 5%. Forty four percent of live births were delivered by elective caesarean section (CS), 27% by emergency CS, 27% by planned vaginal delivery and with one unplanned vaginal delivery. Of 29 live births with viral load <50, 31% were delivered by elective CS, 17% by emergency CS and 52% by vaginal delivery. Fifteen percent of infants were delivered at 32–36 weeks gestation, and 2% at 30 weeks; 16% weighed 1.5–2.5 kg and 16% weighed <1.5 kg. Among 38 of the 51 infants where infection status is already reported, one is perinatally infected.ConclusionsCurrently at least 6% of perinatally infected women in care in the UK and Ireland have experienced one or more pregnancies. Linking paediatric, pregnancy and second generation data will enable further monitoring of pregnancy outcomes in this newly emerging population.

IntroductionDuring pregnancy, LPV/r is a common anchor drug employed to treat the mother's HIV‐1 infection in addition to reducing the risk of mother‐to‐child transmission (MTCT). The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts a comprehensive population‐based surveillance of HIV infection in pregnant women exposed to antiretroviral therapy (ART) in the UK and Ireland; in 2003–2012 over a third of pregnancies reported to the NSHPC involved exposure to LPV/r.MethodsWe undertook a retrospective were descriptive analysis of individual NSHPC patient data, using pregnancy as the unit of observation. Clinical outcomes for pregnancies reported by June 2013, where women were exposed to LPV/r and due to deliver between January 2003 and December 2012, are described.ResultsA total of 4864 LPV/r exposed pregnancies in 4118 women were identified. These resulted in 4702 deliveries with 4759 live and 46 stillborn infants. Seventy five percent of women were born in sub‐Saharan Africa, 13% in the UK or Ireland. Median maternal age at conception was 30 years. Nine hundred and eighty (20%) pregnancies were conceived while taking LPV/r, with a median duration of LPV/r exposure of 270 days. A total of 3884 (80%) pregnancies initiated LPV/r after conception, with a median duration of LPV/r exposure of 107 days. Viral load (VL) close to delivery was available for 4083/4702 (87%) deliveries, with VL <50 c/mL in 73% and <1000 c/mL in 94% of women. VL by timing of LPV/r initiation is shown in Table 1. Sixty three percent of deliveries were by C‐section, of which 62% were classified as elective and 38% as emergency. Among singleton liveborn infants, 13% were born prior to 37 weeks gestation (2.5% <32 weeks) and 15% had birth weight <2500 g (2.3% <1500 g). HIV infection status was available for 4039 (89%) singleton infants. For the periods 2003–2007 and 2008–2012, MTCT rates were 1.1% (95% CI 0.6–1.6) and 0.5% (95% CI 0.2–0.8) respectively. Hundred and thirty four live born children (2.8%) had at least one congenital abnormality reported.ConclusionsIn the NSHPC database, in women exposed to LPV/r during pregnancy in the UK and Ireland, MTCT rates are low and continue to decline, and are similar to rates in the entire NSHPC cohort of women with diagnosed HIV [1]. The congenital abnormality rate is comparable with that reported for the uninfected population in this geographic region.

AbstractIntroductionThe prevalence of gestational diabetes (GD) is increasing globally. While universal risk factors for GD are reasonably well understood, questions remain regarding risks for women living with HIV (WLWH). We aimed to describe GD prevalence, evaluate associated maternal risk factors and assess specific birth outcomes in WLWH in the UK and Ireland.MethodsWe analysed all pregnancies (≥24 weeks' gestation) in women diagnosed with HIV before delivery, reported to the UK‐based Integrated Screening Outcomes Surveillance Service between 2010 and 2020. Every report of GD was considered as a case. A multivariable logistic regression model, adjusted for women with more than one pregnancy fitted with generalized estimating equations (GEE) assessed the effect of independent risk factors.ResultsThere were 10,553 pregnancies in 7916 women, of which 460 (4.72%) pregnancies had reported GD. Overall, the median maternal age was 33 years (Q1:29–Q3:37), and 73% of pregnancies were in Black African women. WLWH with GD (WLWH‐GD) were older (61% vs. 41% aged ≥35 years, p < 0.001) and more likely to be on treatment at conception (74% vs. 64%, p < 0.001) than women without GD. WLWH‐GD were more likely to have a stillbirth (odds ratio [OR]: 5.38, 95% CI: 2.14–13.5), preterm delivery (OR: 2.54, 95% CI: 1.95–3.32) and fetal macrosomia (OR: 1.14, 95% CI: 1.04–1.24). Independent risk factors for GD included estimated year of delivery (GEE‐adjusted odds ratio [GEE‐aOR]: 1.14, 95% CI: 1.10–1.18), advanced maternal age (≥35 years) (GEE‐aOR: 2.87, 95% CI: 1.54–5.34), Asian (GEE‐aOR: 2.63, 95% CI: 1.40–4.63) and Black African (GEE‐aOR: 1.55, 95% CI: 1.13–2.12) ethnicity. Timing and type of antiretroviral therapy showed no evidence of a relationship with GD in multivariable analyses; however, women with a CD4 count ≤350 cells/μl were 27% less likely to have GD than women with CD4 counts >350 cells/μl (GEE‐aOR: 0.73, 95% CI: 0.50–0.96).ConclusionsGD prevalence increased over time among WLWH but was not significantly different from the general population. Maternal age, ethnicity and CD4 count were risk factors based on available data. Stillbirth and preterm delivery were more common in WLWH‐GD than other WLWH over the study period. Further studies are required to build upon these results.

ObjectiveWe are analysing linked public health surveillance data on pregnancies to women living with HIV in the UK and vital registration data on all their children born HIV-free, an under-researched group. We sought to engage women living with HIV to elicit their feedback on our work and set research priorities.
ApproachIn partnership with 4M Net, a national peer-support network for mothers living with HIV, we co-designed and held two online workshops (one workshop a week over two weeks) in March 2022. We designed the workshops to be highly interactive, using a combination of online tools and created a safe space for open discussion. All participants received a preparatory booklet in advance, comprising questions, activities, and space for reflections during the workshops. We also prompted participants to discuss their research priorities with peers and/or family members if they felt comfortable with this.
ResultsIn total, 6 participants attended the two 2-hour long workshops. All participants were from Black ethnic backgrounds, aged 30 years or older and were mothers of children or young adults born HIV-free.
Overall, participants were positive about the programme of research and identified pregnancy, birth, and long-term outcomes in children (especially regarding HIV medication in pregnancy) as being of key importance. They supported the use of linked mental health, hospital, general practice (GP), health visiting and education data to explore pregnancy, health and developmental outcomes among children born HIV-free. Linkage to GP data was identified as a priority by participants, and there was particular interest in addressing knowledge gaps on the mental health of children and young adults born HIV-free.
ConclusionWomen living with HIV are often involved in research around pregnancy, but rarely in research about their children. By working with trusted community partners, we can engage this often marginalised group of parents who understand the value of linked data research exploring the health and wellbeing of their children born HIV-free.

AbstractIntroductionThere is growing interest in health, developmental and survival outcomes of children who are born HIV‐free to women living with HIV (children born HIV‐free). To date, the research agenda has been largely determined by researchers, funders and policy makers, with limited involvement of parents, who are key stakeholders. Researchers at UCL Great Ormond Street Institute of Child Health in partnership with community‐based organisation 4M Network of Mentor Mothers conducted two workshops with parents in March 2022 to establish research priorities for children born HIV‐free, and key considerations for methodological approaches both to research and engagement with the affected communities.DiscussionWhen exploring research on children born HIV‐free, we consider the following: what aspects of current research are aligned with women and parents' priorities, what is missing and what approaches would be preferred. A holistic approach to research on children born HIV‐free should be prioritised, focussing on a breadth of outcomes and how they intersect. Secondary use of existing data sources should be maximised to facilitate this, with a view of monitoring the long‐term effects of fetal antiretroviral drug exposure alongside other key health and developmental outcomes. Involving and engaging with parents, and children where possible, must be at the heart of research design to maximise relevance and impact of findings for the affected communities. Potential barriers to engaging with individuals who were children born HIV‐free include parental disclosure and individuals not identifying as a child born HIV‐free to a mother living with HIV. Stigma‐free language must be incorporated into the vocabulary of researchers and other stakeholders, avoiding reference to exposure; we propose the term "children born HIV‐free."ConclusionsMothers and parents living with HIV should be involved in research about their children born HIV‐free and are key in identifying research priorities so that findings may translate into an impact on their children's health and wellbeing. Meaningful involvement of women living with HIV through trusted community partners is an effective mechanism by which to elicit views on research about their children.

IntroductionHigh rates of hepatotoxicity have been observed among HIV‐positive pregnant women using antiretroviral therapy (ART). However, the extent to which pregnancy affects the risk of ART‐induced hepatotoxicity is unclear since studies in this area have generated conflicting results.Material and MethodsCombined data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC) were used. Alanine aminotransferase (ALT) data were assessed according to the Division of AIDS toxicity guidelines to identify factors associated with liver enzyme elevation (LEE) (grade 1–4). Women starting ART in 2000–11 aged 16–49 years were included irrespective of pregnancy status at ART start. Cox proportional hazards were used to assess the associations between fixed (ethnicity, exposure group, HBV/HCV co‐infection, prior ART use, and age, year, pregnancy status, viral load and CD4 count at ART start) and time‐dependent covariates (pregnancy status, age, year, CD4 count, viral load, duration on ART) and the risk of LEE.ResultsOf the 3426 women included, one‐quarter (25.0%, n=857) were pregnant during follow‐up and 14.4% (n=492) started ART during pregnancy. The rate of LEE was 15/100 person‐years (PY) during pregnancy and 6.1/100 PY outside pregnancy. The risk of LEE was increased during pregnancy (adjusted hazard ratio (aHR) 1.61 [1.26–2.06], p<0.001), including in secondary analysis excluding 493 women pregnant when starting ART. Other factors independently associated with LEE were lower CD4 count (<250 cells/mm3 vs. 251–350 cells/mm3 aHR 1.25 [1.02–1.54], p=0.03), HBV/HCV co‐infection (aHR 1.94 [1.58–2.39], p<0.001), HIV acquired via injecting drug use (aHR 1.61 [1.15–2.24], p=0.01 vs. heterosexually) and calendar year (aHR 1.05 [1.02–1.08], p<0.001 per one year increase). Three ART drugs were associated with increased risk of LEE (efavirenz aHR 1.27 [1.06–1.50], p‐value 0.008; maraviroc 4.19 [1.34–13.1], p=0.01; and nevirapine 1.59 [1.30–1.95], p‐value <0.001). Use of zidovudine was associated with decreased risk of LEE (aHR 0.74 [0.63–0.87], p<0.001) as was increasing time on an NNRTI‐based regimen (aHR 0.91 [0.86–0.96], p<0.001 per additional year).ConclusionsPregnant women were at increased risk of LEE, highlighting the importance of close monitoring of toxicity biomarkers during pregnancy.

Our understanding of congenital infections is based on prospective studies of women infected in pregnancy. The European Union has funded three consortia to study Zika virus (ZIKV), each including a prospective study of pregnant women. Another has been funded by National Institutes of Health. This personal view sets out the study designs required to research ZIKV, and questions whether funding academics in the EU and US to work with collaborators in outbreak areas is an effective strategy. Three years after the 2015-2016 outbreaks, these collaborations have taught us little about ZIKV vertical transmission. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika had largely disappeared. By contrast, prospective studies based on local surveillance and standard of care (SOC) protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These can answer the key questions earlier and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.

AbstractIntroductionAs new antiretrovirals (ARVs), including long‐acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization.DiscussionThis paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under‐reporting (e.g. in voluntary registries), few data sources from resource‐limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource‐limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real‐world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV.ConclusionsLooking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and quality of surveillance in pregnancy. The platform will be leveraged to ensure that appropriate contributions and strategic actions by relevant stakeholders are implemented.

AbstractIntroductionThe UNAIDS 90‐90‐90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland.MethodsUtilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow‐up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression (<200 copies/mL) and good immune status (WHO immunological stage none‐/mild‐for‐age) at last visit in the year were summarized. Among those in care in 2016, outcomes were compared by current age, place of birth (born abroad vs. UK/Ireland) and sex.ResultsOf children in paediatric HIV care at the start of 2010, 2013 and 2016 (n = 1249, 1157, 905 respectively), the proportion in active care during that calendar year was high throughout at 97 to 99%. Of those in active care, the proportion on ART increased from 79% to 85% and 92% respectively (p < 0.001). Among those on ART, the proportion with viral suppression and good immune status was stable at 83% to 86% and 85% to 88%, respectively, across the years. Among children in care in 2016, those aged ≥15 years were less likely to be virally suppressed (79% vs. 91%, p < 0.001) or to have good immune status (78% vs. 94%, p < 0.001) compared to younger children; there were no differences by place of birth or sex.ConclusionsChildren and adolescents in the UK and Ireland national cohort had high retention in care. The proportion on ART increased significantly over time although there was no change in viral suppression or good immune status. Poorer outcomes among adolescents highlight the need for targeted support for this population.

IntroductionHIV‐infected pregnant women are very likely to engage in HIV medical care to prevent transmission of HIV to their newborn. After delivery, however, childcare and competing commitments might lead to disengagement from HIV care. The aim of this study was to quantify loss to follow‐up (LTFU) from HIV care after delivery and to identify risk factors for LTFU.MethodsWe used data on 719 pregnancies within the Swiss HIV Cohort Study from 1996 to 2012 and with information on follow‐up visits available. Two LTFU events were defined: no clinical visit for >180 days and no visit for >360 days in the year after delivery. Logistic regression analysis was used to identify risk factors for a LTFU event after delivery.ResultsMedian maternal age at delivery was 32 years (IQR 28–36), 357 (49%) women were black, 280 (39%) white, 56 (8%) Asian and 4% other ethnicities. One hundred and seven (15%) women reported any history of IDU. The majority (524, 73%) of women received their HIV diagnosis before pregnancy, most of those (413, 79%) had lived with diagnosed HIV longer than three years and two‐thirds (342, 65%) were already on antiretroviral therapy (ART) at time of conception. Of the 181 women diagnosed during pregnancy by a screening test, 80 (44%) were diagnosed in the first trimester, 67 (37%) in the second and 34 (19%) in the third trimester. Of 357 (69%) women who had been seen in HIV medical care during three months before conception, 93% achieved an undetectable HIV viral load (VL) at delivery. Of 62 (12%) women with the last medical visit more than six months before conception, only 72% achieved an undetectable VL (p=0.001). Overall, 247 (34%) women were LTFU over 180 days in the year after delivery and 86 (12%) women were LTFU over 360 days with 43 (50%) of those women returning. Being LTFU for 180 days was significantly associated with history of intravenous drug use (aOR 1.73, 95% CI 1.09–2.77, p=0.021) and not achieving an undetectable VL at delivery (aOR 1.79, 95% CI 1.03–3.11, p=0.040) after adjusting for maternal age, ethnicity, time of HIV diagnosis and being on ART at conception.ConclusionsWomen with a history of IDU and women with a detectable VL at delivery were more likely to be LTFU after delivery. This is of concern regarding their own health, as well as risk for sexual partners and subsequent pregnancies. Further strategies should be developed to enhance retention in medical care beyond pregnancy.

AbstractIntroductionThe 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.DiscussionThe 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.ConclusionsThe 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.

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations. ; This work was supported by the European Union's Horizon 2020 research and innovation programme under grant agreement No 734857 (ZIKAction)

Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4-6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4-39.6%). A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations. ; This work was supported by the European Union's Horizon 2020 research and innovation programme under grant agreement No 734857 (ZIKAction). ; Sí