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Introduction: HIV treatment recommendations have evolved over time, reflecting both growing availability of new antiretrovirals and accumulating evidence on their safe and effective use. We analysed patterns of antiretroviral use among diagnosed pregnant women living with HIV delivering in the UK and Ireland between 2008 and 2018 using national surveillance data., Methods: All singleton pregnancies with known outcomes and known timing of antiretroviral initiation reported to the National Surveillance of HIV in Pregnancy and Childhood were included. Every individual instance of specific antiretroviral use was the unit of analysis in generating a snapshot of antiretroviral use overall and over calendar time. The final analysis was restricted to the 14 most frequently prescribed antiretrovirals., Results: There were 12 099 singleton pregnancies reported during 2008-2018 and a total of 38 214 individual uses of the 14 most commonly prescribed antiretrovirals, the majority of which were started before conception (70.9%). In 2008, 37.7% (482/1279) of pregnancies were conceived under treatment, reaching 80.9% (509/629) by 2018. Patterns of antiretroviral use have changed over time, particularly for third agents. Between 2008 and 2018 the most frequently used protease inhibitor shifted from lopinavir to darunavir, whereas use of integrase inhibitors increased steadily over time., Conclusions: These national surveillance data enable investigation of the 'real-world' use of antiretrovirals in pregnancy on a population level. Findings demonstrate mixed responsiveness of antiretroviral prescription to changes in pregnancy guideline recommendations and may also reflect changes in commissioning and in the characteristics of pregnant women living with HIV., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland., Methods: The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure., Results: A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion., Conclusions: The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.

Objectives: To estimate the incidence of first pregnancy in women living with perinatally acquired HIV (PHIV) in the United Kingdom and to compare pregnancy management and outcomes with age-matched women with behaviourally acquired HIV (BHIV)., Design: The National Study of HIV in Pregnancy and Childhood is a comprehensive, population-based surveillance study that collects demographic and clinical data on all pregnant women living with HIV, their children, and all HIV-infected children in the United Kingdom and Ireland., Methods: The incident rate ratio of first pregnancy was calculated for all women of reproductive age who had been reported to the National Study of HIV in Pregnancy and Childhood as vertically infected children. These women and their pregnancies were compared to age-matched pregnant women with BHIV., Results: Of the 630 women with PHIV reported in the United Kingdom as children, 7% (45) went on to have at least one pregnancy, with 70 pregnancies reported. The incident rate ratio of first pregnancy was 13/1000 woman-years. The BHIV comparison group comprised 118 women (184 pregnancies). Women with PHIV were more likely to be on combined antiretroviral therapy at conception and have a lower baseline CD4 cell count (P < 0.01 for both). In adjusted analysis, PHIV and a low baseline CD4 cell count were risk factors for detectable viral load near delivery; older age at conception and being on combined antiretroviral therapy at conception reduced this risk., Conclusion: Women with PHIV in the United Kingdom have a low pregnancy incidence, but those who become pregnant are at risk of detectable viral load near delivery, reflecting their often complex clinical history, adherence, and drug resistance issues.

Objectives: Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV-positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care., Methods: We used the UK's National Study of HIV in Pregnancy and Childhood for 2009-2014. Data were analysed by fitting logistic regression and Cox proportional hazards models., Results: A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0-15.6 weeks] and booking was significantly earlier during 2012-2014 vs. 2009-2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1-24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later., Conclusions: Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART., (© 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe., Methods: Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV-positive women at delivery and between 1 and 12 months postpartum. Depressive symptoms in the previous month were assessed using a self-report screening tool. Other data collected included demographics, antiretroviral therapy (ART)-related self-efficacy, and perceptions of risks/benefits of interventions to prevent mother-to-child transmission (PMTCT). Characteristics of women with and without a positive depression screening test result were compared using Fisher's exact test and χ2 test for categorical variables., Results: A quarter (27% (49/180) antenatally and 25% (57/228) postnatally) of participants screened positive for depressive symptoms. Antenatal risk factors were living alone (58% (7/12) vs. 25% (42/167) p = 0.02), being somewhat/terribly bothered by ART side effects (40% (17/43) vs. 23% (30/129) not /only slightly bothered, p = 0.05) and having lower ART-related self-efficacy (43% (12/28) vs. 23% (25/110) with higher self-efficacy, p = 0.05). Postnatally, single mothers were more likely to screen positive (44% (20/45) vs. 21% (18/84) of cohabiting and 19% (19/99) of married women, p < 0.01) as were those unsure of the effectiveness of neonatal prophylaxis (40% (20/45) vs. 18% (28/154) sure of effectiveness, p < 0.01), those worried that neonatal prophylaxis could harm the baby (30% (44/146) vs. 14% (10/73) not worried p < 0.01) and those not confident to ask for help with taking ART (48% (11/23) vs. 27% (10/37) fairly confident and 15 % (4/26) confident that they could do this). Of women who reported wanting help for their depressive symptoms, 82% (37/45) postnatally but only 31% (12/39) antenatally were already accessing peer counselling, treatment adherence programmes, support groups or social services., Conclusions: A quarter of women screened positive for depression. Results highlight the need for proactive strategies to identify depressive symptoms, and an unmet need for provision of mental health support in the perinatal period for HIV-positive women in Ukraine.

To estimate HCV seroprevalence in subpopulations of women delivering live-born infants in the North Thames region in England in 2012, an unlinked anonymous (UA) cross-sectional survey of neonatal dried blood spot samples was conducted. Data were available from 31467 samples from live-born infants received by the North Thames screening laboratory. Thirty neonatal samples had HCV antibodies, corresponding to a maternal seroprevalence of 0·095% (95% confidence interval 0·067-0·136). Estimated HCV seroprevalences in women born in Eastern Europe, Southern Asia and the UK were 0·366%, 0·162% and 0·019%, respectively. For women born in Eastern Europe seroprevalence was highest in those aged around 27 years, while in women born in the UK and Asia-Pacific region, seroprevalence increased significantly with age. HCV seroprevalence in UK-born women whose infant's father was also UK-born was 0·016%. One of the 30 HCV-seropositive women was HIV-1 seropositive. Estimated HCV seroprevalence for women delivering live-born infants in North Thames in 2012 (0·095%) was significantly lower than that reported in an earlier UA survey in 1997-1998 (0·191%). Data indicate that the cohort of UK-born HCV-seropositive women is ageing and that, in this area of England, most perinatally HCV-exposed infants were born to women themselves born in Southern Asia or Eastern Europe.

Background: Women living with HIV are potentially at increased risk of adverse pregnancy outcomes, due to a range of factors, including immunosuppression, use of combination antiretroviral therapy (ART), and injecting drug use. Rates of mother-to-child transmission of HIV in Ukraine have declined to around 2-4%, but little is known about other pregnancy outcomes in this setting. We used data from an observational prospective cohort study to assess pregnancy outcomes among HIV-positive women in Ukraine., Methods: The European Collaborative Study (ECS) in EuroCoord is a continuing cohort study, established in Ukraine in 2000. Eligible women are those with a diagnosis of HIV infection before or during pregnancy (including intrapartum) who deliver liveborn babies at seven sites. Maternal sociodemographic, HIV-related, and delivery (mother and infant) data were collected with study-specific questionnaires. We used Poisson regression models to identify factors associated with preterm delivery (before 37 weeks' gestation) and small weight for gestational age (less than the tenth percentile of weight for gestational age), based on complete cases., Findings: Between January, 2000, and July, 2012, data were collected on 8884 HIV-positive mother and liveborn infant pairs. Median maternal age was 26·5 years (IQR 23·1-30·3). 832 (11%) women had WHO stage 3 or 4 HIV and 1474 (17%) had a history of injecting drug use. 7348 (83%) had received antenatal ART. Among 7435 for whom ART type was available, 4396 (50%) had received zidovudine monotherapy and 2949 (33%) combination ART. Preterm delivery was seen in 780 (9%, 95% CI 8-9) of 8860 births overall and in 77 (9%, 7-11) of 889 babies with small size for gestational age. Factors associated with preterm delivery were history of injecting drug use (adjusted risk ratio 1·64, 95% CI 1·38-1·95), no ART (2·94, 2·43-3·57 vs zidovudine monotherapy), antenatal combination ART (1·40, 1·14-1·73 vs zidovudine monotherapy), WHO stage 4 HIV (2·42, 1·71-3·41 vs WHO stage 1), and being in the most socially deprived group (1·38, 1·11-1·71). Small size for gestational age was associated with history of injecting drug use (adjusted RR 1·39, 95% CI 1·16-1·65), most socially deprived (1·32, 1·09-1·61), no ART (1·60, 1·32-1·94 vs zidovudine monotherapy), and antenatal combination ART (1·33, 1·12-1·60 vs zidovudine monotherapy)., Interpretation: Some risk factors for adverse pregnancy outcomes were directly associated with HIV and treatment and others were shared with the general antenatal population. Monitoring of pregnancy outcomes in Ukraine will be important as use of antenatal combination ART increases., Funding: European Union Seventh Framework Programme, Wellcome Trust., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Poor adherence to antiretroviral therapy (ART) is associated with HIV disease progression and, during pregnancy, increased mother-to-child transmission risk. In Ukraine, access to combination ART is expanding but data on adherence are scarce., Methods: Cross-sectional surveys of HIV-positive women were conducted i) at delivery (on antenatal ART adherence) and ii) during the first year postpartum (on ART adherence in the preceding four weeks). Factors associated with a score ≤ 11 on the self-report Case Adherence Support Evaluation (CASE) index or ≥ 1 self-reported missed dose were assessed using Fisher's exact test., Results: Of 185 antenatal participants and 102 postnatal participants, median ages were 27.5 and 29.5 years respectively: 28% (50/180) and 27% (26/98) reported an unplanned pregnancy, and 13% (24/179) and 17% (17/98) an illicit drug-use history (excluding marijuana). One quarter (49/180 antenatally, 27/101 postnatally) screened positive for depression. The proportion reporting 'low' ART-related self-efficacy (i.e. unable to do ≥ 1/5 ART-taking activities) was 20% (28/141) antenatally and 17% (11/66) postnatally. Antenatally, 14% (95% CI 10-21%) had a CASE score ≤ 11 and 35% (95% CI 28-42%) reported missing ≥ 1 dose. Factors associated with a CASE score ≤ 11 were unplanned pregnancy (25% (12/48) vs. 11% (13/120) where planned, p = 0.03) and living with extended family (23% (13/57) vs. 10% (12/125) living with partner/alone, p = 0.04). Self-report of ≥ 1 missed dose antenatally was additionally associated with younger age (p = 0.03) and lower self-efficacy (50% (14/28) reported ≥ 1 missed dose vs. 28% (30/108) of those with high self-efficacy, p = 0.04). Of 102 postnatal participants, 8% (95% CI 4-15%) had a CASE score ≤ 11 and 31% (95% CI 22-41%) reported ≥ 1 missed dose. Of 11 women with low self-efficacy, 3 (27%) had a CASE score ≤ 11 compared with 3/55 (5%) of those with high self-efficacy (p = 0.05). Current smokers more commonly reported ≥ 1 missed dose postnatally (50% (13/26) vs. 25% (18/72) of non-smokers, p = 0.03)., Conclusions: Our results highlight unmet needs for counselling and support. We identify some groups at risk of poor ART adherence, including women with markers of social vulnerability and those with low ART-related self-efficacy, who may benefit from targeted interventions.

During their second pregnancy with diagnosed HIV (n = 1177), two-fifths of women in the UK/Ireland not on antiretroviral therapy (ART) at conception had an immunological indication for treatment (CD4(+) <350 cells/μl), of whom nearly half had CD4(+) at least 350 cells/μl in their previous pregnancy. Those initiating ART during pregnancy had a 4.3-fold increased odds of detectable viral load at delivery compared with those conceiving on treatment, suggesting that continuation of ART after pregnancy may be beneficial for many women.

Objective: The aim of this study was to assess predicted Down syndrome risk, based on three serum analytes (triple test), with HIV infection status and antiretroviral therapy regimen., Methods: Screening results in 72 HIV-positive women were compared with results from age-matched and race-matched HIV-negative controls. Mean concentrations of each analyte were compared by serostatus and antiretroviral therapy. Observed Down syndrome incidence in the offspring of HIV-positive women was calculated from national HIV surveillance data., Results: Overall, women with HIV had a significantly higher probability of receiving a 'high-risk' result than uninfected controls (p = 0.002). Compared with matched uninfected controls, women with HIV infection had significantly higher human chorionic gonadotrophin, lower unconjugated estriol, and higher overall predicted risk of their infant having Down syndrome (1/6250 vs. 1/50 000 p = < 0.001). National surveillance data show no evidence of higher than expected incidence of Down syndrome in the offspring of HIV-positive women., Conclusions: HIV infection impacts the serum analytes used to assay for Down syndrome risk resulting in a high rate of 'high risk' results. However, there is no population-based association between maternal HIV infection and Down syndrome. Care should be taken when interpreting high-risk serum screening results in HIV-positive women to avoid unnecessary invasive diagnostic procedures., (© 2013 John Wiley & Sons, Ltd.)

Objective: To explore the pattern of repeat pregnancies among diagnosed HIV-infected women in the United Kingdom and Ireland, estimate the rate of these sequential pregnancies, and investigate the demographic and clinical characteristics of women experiencing them., Design: Diagnosed HIV-infected pregnant women are reported through an active confidential reporting scheme to the National Study of HIV in Pregnancy and Childhood., Methods: Pregnancies occurring during 1990-2009 were included. Multivariable analyses were conducted fitting Cox proportional hazards models., Results: There were 14,096 pregnancies in 10,568 women; 2737 (25.9%) had 2 or more pregnancies reported. The rate of repeat pregnancies was 6.7 (95% confidence interval: 6.5 to 7.0) per 100 woman-years. The proportion of pregnancies in women who already had at least 1 pregnancy reported increased from 20.3% (32 of 158) in 1997 to 38.6% (565 of 1465) in 2009 (P < 0.001). In multivariable analysis, the probability of repeat pregnancy significantly declined with increasing age at first pregnancy. Parity was also inversely associated with repeat pregnancy. Compared with women born in the United Kingdom or Ireland, those from Europe, Eastern Africa, and Southern Africa were less likely to have a repeat pregnancy, whereas women from Middle Africa and Western Africa were more likely to. Maternal health at first pregnancy was not associated with repeat pregnancy., Conclusions: The number of diagnosed HIV-infected women in the United Kingdom and Ireland experiencing repeat pregnancies is increasing. Variations in the probability of repeat pregnancies, according to demographic and clinical characteristics, are an important consideration when planning reproductive health services and HIV care for people living with HIV.

UK and Ireland guidelines state that all pregnant women should have their first antenatal care appointment by 13 weeks of pregnancy (antenatal booking). We present the results of an analysis looking at the association between maternal ethnicity and late antenatal booking in HIV-positive women in the UK and Ireland. We analysed data from the National Study of HIV in Pregnancy and Childhood (NSHPC). We included all pregnancies in women who were diagnosed with HIV before delivery and had an estimated delivery date between 1 January 2008 and 31 December 2009. Late booking was defined as antenatal booking at 13 weeks or later. The baseline reference group for all analyses comprised women of "white" ethnicity. Logistic regression models were fitted to estimate adjusted odds ratios (AOR). There were 2721 eligible reported pregnancies; 63% (1709) had data available on antenatal care booking date. In just over 50% of pregnancies (871/1709), the antenatal booking date was ≥13 weeks of pregnancy (i.e., late booking). Women diagnosed with HIV during the current pregnancy were more likely to present for antenatal care late than those previously diagnosed (59.1% vs. 47.5%, p<0.001). Where women knew their HIV status prior to becoming pregnant, the risk of late booking was raised for those of African ethnicity (AOR 1.80; 95% confidence interval (CI) 1.14, 2.82; p=0.011). In women diagnosed with HIV during pregnancy, the risk of late booking was also higher for women of African ethnicity (AOR 2.98: 95% CI 1.45, 6.11; p=0.003) and for women of other black ethnicity (AOR 3.74: 95% CI 1.28, 10.94; p=0.016). Overall, women of African or other black ethnicity were more likely to book late for antenatal care compared with white women, regardless of timing of diagnosis. This may have an adverse effect on maternal and infant outcomes, including mother-to-child transmission of HIV.

Background: Increasing numbers of women in resource-rich settings are prescribed zidovudine (ZDV)-sparing highly active antiretroviral therapy (HAART) in pregnancy. We compare ZDV-sparing with ZDV-containing HAART in relation to maternal viral load at delivery, mother-to-child transmission (MTCT) of HIV, and congenital abnormality., Methods: This is an analysis of data from the National Study of HIV in Pregnancy and Childhood and the European Collaborative Study. Data on 7573 singleton births to diagnosed HIV-infected women between January 2000 and June 2009 were analyzed. Logistic regression models were fitted to estimate adjusted odds ratios (AORs)., Results: Overall, 15.8% (1199 of 7573) of women received ZDV-sparing HAART, with increasing use between 2000 and 2009 (P < 0.001). Nearly a fifth (18.4%) of women receiving ZDV-sparing HAART in pregnancy had a detectable viral load at delivery compared with 28.6% of women on ZDV-containing HAART [AOR 0.90; 95% confidence interval (CI): 0.72 to 1.14, P = 0.4]. MTCT rates were 0.8% and 0.9% in the ZDV-sparing and ZDV-containing groups, respectively (AOR 1.81; 95% CI: 0.77 to 4.26, P = 0.2). The congenital abnormality rate was the same in both groups (2.7%, AOR 0.98; 95% CI: 0.66 to 1.45, P = 0.9), with no significant difference between the groups in a subanalysis of pregnancies with first trimester HAART exposure (AOR 0.79; 95% CI: 0.48 to 1.30, P = 0.4)., Conclusions: We found no difference in risk of detectable viral load at delivery, MTCT, or congenital abnormality when comparing ZDV-sparing with ZDV-containing HAART. With increasing use of ZDV-sparing HAART, continued monitoring of pregnancy outcomes and long-term consequences of in utero exposure to these drugs is required.

Background: Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk., Methods: Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1-13 days of treatment was investigated, and associated factors explored using logistic regression models., Results: Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-2003 to 5% in 2004-2009 (χ(2)=8.73; P<0.01). A further 41 (2%) received 1-13 days of ART. One-third (64/171) of women with 'insufficient' (0 or 1-13 days) antenatal ART had a late HIV diagnosis (in the third trimester or intrapartum), but half (85/171) were diagnosed before conception. Pre-term delivery <34 weeks was associated with receipt of no and 1-13 days antenatal ART (adjusted odds ratios [ORs] 2.9 [P<0.01] and 4.5 [P<0.01], respectively). History of injecting drug use was associated with an increased risk of no ART (adjusted OR 2.9; P<0.01) and severe symptomatic HIV disease with a decreased risk (adjusted OR 0.2; P<0.01). MTCT rates were 1.1% (15/1,318) among women with ≥14 days antenatal ART and 7.4% (10/136) among those with insufficient ART., Conclusions: Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care., (© 2011 International Medical Press)

Objective:  To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women., Design:   Combined analysis of data from three observational studies., Setting:  USA and Europe., Population:   A total of 19, 585 singleton infants born to HIV-infected women, 1990-2006., Methods:   Data from the Pediatric Spectrum of HIV Disease project (PSD), a US monitoring study, the European Collaborative Study (ECS), a consented cohort study, and the National Study of HIV in Pregnancy and Childhood (NSHPC), the United Kingdom and Ireland surveillance study., Main Outcome Measure:   Preterm delivery rate (<37 weeks of gestation)., Results:   Compared with monotherapy, HAART was associated with increased preterm delivery risk in the ECS (adjusted odds ratio [AOR] 2.40, 95% CI 1.49-3.86) and NSHPC (AOR 1.43, 95% CI 1.10-1.86), but not in the PSD (AOR 0.92, 95% CI 0.67-1.26), after adjusting for relevant covariates. Because of heterogeneity, data were not pooled for this comparison, but heterogeneity disappeared when HAART was compared with dual therapy (P = 0.26). In a pooled analysis, HAART was associated with 1.5-fold increased odds of preterm delivery compared with dual therapy (95% CI 1.19-1.87, P=0.001), after adjusting for covariates., Conclusions:   Heterogeneity in the association between HAART and preterm delivery was not explained by study design, adjustment for confounders or a standard analytical approach, but may have been the result of substantial differences in populations and data collected. The pooled analysis comparing HAART with dual therapy showed an increased risk of preterm delivery associated with HAART.

Background: Highly active antiretroviral therapy (HAART) for pregnant HIV-positive women reduces the risk of mother-to-child transmission, but is associated with an increased risk of preterm delivery (<37 weeks gestation). We aimed to quantify the incremental risk-benefit ratio for HAART compared with zidovudine monotherapy with respect to these outcomes., Methods: Two-stage Monte Carlo simulation methods were used to estimate the risk-benefit ratio for HAART in pregnancy. Estimates of mother-to-child transmission and preterm delivery rates were obtained from UK and Ireland surveillance data collected through the National Study of HIV in Pregnancy and Childhood., Results: At a population level, HAART was associated with a more than sevenfold reduction in mother-to-child transmission compared with zidovudine monotherapy (adjusted odds ratio [AOR] 0.13, 95% confidence interval [CI] 0.06-0.27), but with a 1.4-fold increased odds of preterm delivery (AOR 1.43, 95% CI 1.10-1.86) and twofold increased odds of severe preterm delivery (<32 weeks; AOR 2.06, 95% CI 1.09-3.88). The incremental risk-benefit ratio for HAART in pregnancy compared with monotherapy was 0.63 (95% simulation interval 0.06-1.96) additional preterm births and 0.23 (95% simulation interval -0.02-0.88) severe preterm births for each infection prevented., Conclusions: It is estimated that for every 100 HIV transmissions prevented through the use of HAART (rather than monotherapy), 63 additional preterm deliveries would occur, including 23 at <32 weeks gestation. Interpretation of these ratios is context-dependent and requires additional information about morbidity, mortality and costs associated with the outcomes.

Objective: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race., Methods: Data on > or = 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection., Results: The change in HIV RNA over pregnancy varied significantly by race (p=0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% CI -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% CI -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% CI 0.08, 0.83) than in white women., Conclusions: Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding.

Objective: To explore the rate of reported congenital abnormalities in infants exposed to antiretroviral therapy in utero., Design: Comprehensive national surveillance study in the UK and Ireland., Methods: Births to diagnosed HIV-infected women are reported to the National Study of HIV in Pregnancy and Childhood. Infants born between 1990 and 2007 were included., Results: The rate of reported major and minor congenital abnormality was 2.8% (232/8242) overall, and there was no significant difference by timing of ART exposure: 2.8% (14/498) in unexposed infants, 2.7% (147/5427) following second or third trimester exposure, and 3.1% (53/1708) following first trimester exposure (P = 0.690). There was no difference in abnormality rates by class of ART exposure in the first trimester (P = 0.363), and no category of abnormality was significantly associated with timing of ART, although numbers in these groups were small. There was no increased risk of abnormalities in infants exposed to efavirenz (P = 0.672) or didanosine (P = 0.816) in the first trimester., Conclusion: These findings, based on a large, national, unselected population provide further reassurance that ART in utero does not pose a major risk of fetal anomaly.

Objective: To describe the changing demographic profile of diagnosed HIV-infected pregnant women over time and trends in pregnancy outcome, uptake of interventions and mother-to-child transmission., Design: National surveillance study., Setting: UK and Ireland., Population: Diagnosed HIV-infected pregnant women, 1990-2006., Methods: Active surveillance of obstetric and paediatric HIV conducted through the National Study of HIV in Pregnancy and Childhood., Main Outcome Measures: Maternal characteristics, pregnancy outcome, use of antiretroviral therapy, mode of delivery and mother-to-child transmission., Results: A total of 8327 pregnancies were reported, increasing from 82 in 1990 to 1394 in 2006, with an increasing proportion from areas outside London. Injecting drug use as the reported risk factor for maternal HIV acquisition declined from 49.2% (185/376) in 1990-1993 to 3.1% (125/4009) in 2004-2006 (P < 0.001), while the proportion of women born in sub-Saharan Africa increased from 43.5% (93/214) in 1990-1993 to 78.6% (3076/3912) in 2004-2006 (P < 0.004). Reported pregnancy terminations decreased from 29.6% (111/376) in 1990-1993 to 3.4% (135/4009) in 2004-2006 (P < 0.001). Most (56.4%, 3717/6593) deliveries were by elective caesarean section, with rates highest in 1999 (66.4%, 144/217). Vaginal deliveries increased from 16.6% (36/217) in 1999 to 28.3% (321/1136) in 2006 (P < 0.001). Use of antiretroviral therapy in pregnancy increased over time, reaching 98.4% (1092/1110) in 2006, and the overall mother-to-child transmission rate declined from 18.5% (35/189) in 1990-1993 to 1.0% (29/2832) in 2004-2006., Conclusions: The annual number of reported pregnancies increased dramatically between 1990 and 2006, with changing demographic and geographic profiles and substantial changes in pregnancy management and outcome.

Aim: In the United Kingdom (UK) and Ireland, avoidance of breastfeeding and alternative combinations of antiretroviral therapy regimen and mode of delivery are recommended according to maternal clinical status. The aim of this analysis was to explore the impact of different strategies to prevent mother-to-child transmission at a population level., Design: Comprehensive national surveillance study., Methods: Pregnancies in diagnosed HIV-infected women in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood; infant infection status is subsequently reported. Factors associated with transmission in this observational study were explored for singleton births between 2000 and 2006., Results: The overall mother-to-child transmission rate was 1.2% (61/5151, 95% confidence interval: 0.9-1.5%), and 0.8% (40/4864) for women who received at least 14 days of antiretroviral therapy. Transmission rates following combinations recommended in British guidelines were 0.7% (17/2286) for highly active antiretroviral therapy with planned Caesarean section, 0.7% (4/559) for highly active antiretroviral therapy with planned vaginal delivery, and 0% (0/464) for zidovudine monotherapy with planned Caesarean section (P = 0.150). Longer duration of highly active antiretroviral therapy was associated with reduced transmission after adjusting for viral load, mode of delivery and sex (adjusted odds ratio = 0.90 per week of highly active antiretroviral therapy, P = 0.007). Among 2117 infants born to women on highly active antiretroviral therapy with viral load less than 50 copies/ml, only three (0.1%) were infected, two with evidence of in-utero transmission., Conclusion: Sustained low HIV transmission rates following different combinations of interventions in this large unselected population are encouraging. Current options for treatment and delivery offered to pregnant women according to British guidelines appear to be effective.

Background: There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women., Methods: Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn., Results: Protease inhibitor-based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16-3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not., Conclusions: In this study, nevirapine-based HAART (compared with PI [mainly nelfinavir]-based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression.

Objective: To explore the association between antiretroviral therapy in pregnancy and premature delivery, birthweight, stillbirth and neonatal mortality, in pregnancies in HIV-infected women delivering between 1990 and 2005., Design: Pregnancies in women with diagnosed HIV infection in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood (NSHPC) through a well-established surveillance scheme., Results: The prematurity rate (< 37 weeks gestation) was higher in women on highly active antiretroviral therapy (HAART) (14.1%, 476/3384) than in women on mono/dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, maternal age, clinical status and injecting drug use as the source of HIV acquisition [adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI), 1.19-1.93; P = 0.001]. Delivery at < 35 weeks was even more strongly associated with HAART (AOR = 2.34; 95% CI, 1.64-3.37; P < 0.001). The effect was the same whether or not HAART included a protease inhibitor. In comparison with exposure to mono/dual therapy, exposure to HAART was associated with lower birthweight standardized for gestational age (P < 0.001), and an increased risk of stillbirth (AOR = 2.27; 95% CI, 0.96-5.41; P = 0.063)., Conclusions: These findings, based on comprehensive population surveillance, demonstrate an increased risk of prematurity associated with HAART, and a possible association with other perinatal outcomes, including stillbirth and birthweight. Although the beneficial effects of antiretroviral therapy on mother-to-child transmission are indisputable, monitoring antiretroviral therapy in pregnancy remains a priority.

We analyse the distribution of HIV-1 subtypes in HIV-1-seropositive samples from 333,270 residual neonatal dried blood spot samples tested for routine newborn screening tests in the UK between July 1999 and December 2002. Of the 813 antibody-positive samples shown to contain passively acquired, maternal HIV-1 for which subtyping was attempted, 333 (41%) could not be subtyped due to cross-reactivity or low values of the assay results, and 480 (59%) were classified as B (35, 7.3%) or non-B (445, 92.7%). The proportions of subtyped B samples differed significantly (P=0.004) between those from neonates whose mothers were born in the UK (21.4%) and those from neonates whose mothers were known to be born abroad (7%). Using a serological approach to establish viral serotype, we document the distribution of HIV-1 subtypes in infected pregnant women in the UK.

Antiretroviral therapy (ART) in pregnancy substantially reduces the risk of mother-to-child transmission of HIV, but concerns exist about the potential for teratogenic effects. This analysis was undertaken to explore the relation between ART in pregnancy and birth defects in infants born to HIV-infected women in the United Kingdom and Ireland between 1990 and 2003. Comprehensive obstetric and pediatric HIV surveillance is carried out through the National Study of HIV in Pregnancy and Childhood. Congenital abnormalities were reported in 101 of 3172 infants (100 of 3120 pregnancies). There was no statistically significant association between the prevalence of congenital abnormalities and exposure to ART overall: 3.4% (90 of 2657 pregnancies) in exposed pregnancies and 2.2% (10 of 463 pregnancies) in nonexposed pregnancies (P = 0.166); prevalence was similar whether or not exposure occurred in the first trimester: 3.7% (20 of 541 pregnancies) after early exposure and 3.1% (80 of 2579 pregnancies) without early exposure (P = 0.476). There was also no significant association with type of ART in early pregnancy (ie, highly active antiretroviral therapy [HAART] vs. mono- or dual therapy, HAART with protease inhibitor and/or nonnucleoside reverse transcriptase inhibitor). The lack of association was maintained after adjustment for potential confounding factors. These findings are reassuring, but continued monitoring is essential in view of the increasing number of women on therapy at conception and the likely continuing diversity of drug regimens.

Background: HIV contributes substantially to child mortality, but factors underlying these deaths are inadequately described. With individual data from seven randomised mother-to-child transmission (MTCT) intervention trials, we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors., Methods: Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age; and late infection by a negative PCR test at or after 4 weeks of age, followed by a positive test. Mortality rate was expressed per 1000 child-years. We investigated the effect of maternal health, infant HIV infection, feeding practices, and age at acquisition of infection on mortality assessed with Cox proportional hazards models, and allowed for random effects for trials grouped geographically., Findings: 378 (11%) of 3468 children died. By age 1 year, an estimated 35.2% infected and 4.9% uninfected children will have died; by 2 years of age, 52.5% and 7.6% will have died, respectively. Mortality varied by geographical region, and was associated with maternal death (adjusted odds ratio 2.27, 95% CI 1.62-3.19), CD4+ cell counts <200 per microL (1.91, 1.39-2.62), and infant HIV infection (8.16, 6.43-10.33). Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children. In infected children, mortality was significantly lower for those with late infection than those with early infection (0.52, 0.39-0.70). This effect was also seen in analyses of survival from the age at infection (0.74, 0.55-0.99)., Interpretation: These findings highlight the necessity for timely antiretroviral care, for support for HIV-infected women and children in developing countries, and for assessment of prophylactic programmes to prevent MTCT, including child mortality and infection averted.

We followed up a cohort of 446 toxoplasma-infected pregnant women to determine the median and variability of the duration of positive toxoplasma-IgM (immunoglobulin M) results measured by an immunofluorescence test (IFT) and an immunosorbent agglutination assay (ISAGA). IgM antibodies were detected for longer using the ISAGA test [median 12.8 months, interquartile range (IQR) 6.9-24.9] than the IFT (median 10.4, IQR 7.1-14.4), but the variability between individuals in the duration of IgM positivity was greatest for the ISAGA test. IgM-positive results persisted beyond 2 years in a substantial minority of women (27.1% ISAGA, 9.1% IFT). Variation in the duration of the IgM response measured by ISAGA and IFT limit their usefulness for predicting the timing of infection in pregnant women. However, measurement of IgM and IgG antibodies in a cross-sectional serosurvey offers an efficient method for estimating the incidence of toxoplasma infection.

In order to derive more accurate estimates of HIV infection among the general population in Great Britain from unlinked anonymous neonatal seroprevalence data, the differential HIV and fertility patterns amongst groups of women were explored. The HIV risk in women was estimated using neonatal seroprevalence data and reports of diagnoses of HIV infection in pregnant women. Live birth rates were estimated using population data and these were supplemented using data from a prospective European cohort of HIV-infected pregnant women. HIV prevalence was higher in women born in sub-Saharan Africa (SSA) and injecting drug users (IDUs) (2.50% and 0.29% respectively in London) compared to other women (0.068%). Fertility was also higher in women born in SSA (OR 1.33 using population data), whilst IDUs were more likely to have had a previous termination (OR 1.48 using the European cohort of HIV-infected pregnant women data). We conclude that when unlinked anonymous neonatal seroprevalence data is used to estimate general population prevalence, adjustments need to be made for fertility differentials in population subgroups at varying risk of HIV.

Objective: To describe trends in the prevalence of HIV in an ethnically diverse population of pregnant women in the United Kingdom., Methods: Data on parental country of birth from national birth registration records were linked to neonatal dried blood spot samples routinely collected for neonatal screening in the North Thames region between 1998 and 2002. Identifiers were subsequently irreversibly deleted prior to establishing maternal HIV status by testing the neonatal samples., Results: A total of 491 213 dried blood spot samples were collected, and 490 879 (99.93%) were tested for HIV. Of these, 1029 were seropositive. There was an overall significant increasing trend (P-value = 0.001) between 1998 and 2002. Maternal region of birth was available for 89.8% of HIV-infected samples, and, among these, 80.5% of mothers were born in sub-Saharan Africa and 11.1% in the UK. The highest prevalences of HIV were in women born in sub-Saharan Africa (2.09%). If both parents were born in the UK, overall seroprevalence was 0.016%., Conclusion: HIV infection in pregnant women in the UK continues to occur predominantly in women born in sub-Saharan Africa with prevalence in this group increasing significantly. Although the absolute number of HIV-infected women rose in some other groups, there was no evidence for a statistically significant rise in HIV prevalence in women born outside sub-Saharan Africa. Over 93% of children at risk of vertical transmission of HIV had at least one parent born abroad. This paper underlines the value of data linkage in monitoring HIV prevalence in a diverse population.