Claire L Townsend

Low rates of mother-to-child transmission of HIV following effective pregnancy interventions in the United Kingdom and Ireland, 2000-2006

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.

Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland

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.

Earlier initiation of ART and further decline in mother-to-child HIV transmission rates, 2000-2011

Objectives:To analyze mother-to-child HIV transmission (MTCT) rates over time in light of changes in management, demographic, and pregnancy characteristics. Design:Population-based surveillance data on diagnosed HIV-positive women and their infants are routinely collected in the UK and Ireland. Methods:A total of 12 486 singleton pregnancies delivered in 2000–2011 were analyzed. HIV infection status was available for 11 515 infants (92.2%). Results:The rate of MTCT declined from 2.1% (17/816) in 2000–2001 to 0.46% (nine of 1975, 95% confidence interval: 0.21–0.86%) in 2010–2011 (trend, P = 0.01), because of a combination of factors including earlier initiation of antenatal combination antiretroviral therapy (cART). Excluding 63 infants who were breastfed or acquired HIV postnatally, MTCT risk was significantly higher for all modes of delivery in women with viral load of 50–399 copies/ml (1.0%, 14/1349), compared with viral load of less than 50 copies/ml (0.09%, six of 6347, P <0.001). Among the former (viral load 50–399 copies/ml), the risk of MTCT was 0.26% (two of 777) following elective cesarean section and 1.1% (two of 188) following planned vaginal delivery (P = 0.17), excluding in-utero transmissions. MTCT probability declined rapidly with each additional week of treatment initially, followed by a slower decline up to about 15 weeks of cART, with substantial differences by baseline viral load. Conclusion:MTCT rates in the UK and Ireland have continued to decline since 2006, reaching an all-time low of 5 per 1000 in 2010–2011. This was primarily because of a reduction in transmissions associated with late initiation or nonreceipt of antenatal cART, and an increase in the proportion of women on cART at conception.

Trends in management and outcome of pregnancies in HIV-infected women in the UK and Ireland, 1990-2006

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.

Long-term Outcomes of Congenital Cytomegalovirus Infection in Sweden and the United Kingdom

BACKGROUND Congenital cytomegalovirus (CMV) is an important cause of neurological problems, particularly sensorineural hearing loss, but data on long-term sequelae and the impact of nonprimary maternal infection are limited. We report updated findings on childhood outcomes from 2 large prospective studies. METHODS Pregnant women in Malmö, Sweden, and London, United Kingdom, were included between 1977 and 1986, and newborns were screened for CMV (virus culture of urine or saliva). Cases and matched controls underwent regular, detailed developmental assessments up to at least age 5 years. RESULTS One hundred seventy-six congenitally infected infants were identified among >50 000 screened (Malmö: 76 [4.6/1000 births]; London: 100 [3.2/1000 births]); 214 controls were selected. Symptoms were recorded in 11% of CMV-infected neonates (19/176) and were mostly mild; only 1 neonate had neurological symptoms. At follow-up, 7% of infants (11/154) were classified as having mild, 5% (7/154) moderate, and 6% (9/154) severe neurological sequelae. Four of 161 controls (2%) had mild impairment. Among children symptomatic at birth, 42% (8/19) had sequelae, versus 14% (19/135) of the asymptomatic infants (P = .006). All moderate/severe outcomes were identified by age 1; mild sequelae were first identified at age 2-5 years in 6 children, and age 6-7 years in 3. Among the 16 children with moderate/severe outcomes, 2 had mothers with confirmed and 7 with presumed nonprimary infection. CONCLUSIONS Moderate or severe outcomes were reported in 11% of children with congenital CMV identified through population screening, all by 1 year; all impairment detected after this age was mild. Nonprimary infections contributed substantially to the burden of childhood congenital CMV disease.

Antiretroviral therapy and preterm delivery—a pooled analysis of data from the United States and Europe

Please cite this paper as: Townsend C, Schulte J, Thorne C, Dominguez K, Tookey P, Cortina‐Borja M, Peckham C, Bohannon B, Newell M, for the Pediatric Spectrum of HIV Disease Consortium, the European Collaborative Study and the National Study of HIV in Pregnancy and Childhood. Antiretroviral therapy and preterm delivery—a pooled analysis of data from the United States and Europe. BJOG 2010;117:1399–1410.

Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990-2007.

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.

Surveillance of congenital cytomegalovirus in the UK and Ireland

Objective To explore the presentation and management of congenital cytomegalovirus (CMV) identified through routine clinical investigations, and ascertain outcome in early childhood. Design Active population-based surveillance. Setting UK and Ireland. Methods Infants born in 2001–2002 with confirmed or suspected congenital CMV infection were reported through the British Paediatric Surveillance Unit, and clinicians completed questionnaires on presentation, diagnosis, management and subsequent outcome. Results 86 confirmed and 70 possible cases of congenital CMV infection were reported. Over a third (27/72) of singleton infants with confirmed and 44% (27/61) with possible congenital infection were preterm (<37 weeks gestation). Among confirmed cases, 75% (64/85) presented with neonatal manifestations compatible with congenital CMV, over half (34/64) of whom had neurological signs; 17 infants were treated with gancyclovir. Among confirmed cases with information on outcome, 31% (24/78) were developing normally, 18% (14/78) had mild, 24% (19/78) moderate and 14% (11/78) severe sequelae, and 13% (10/78) had died. Median age at follow-up among survivors was 18 months (IQR 15–22 months). Children with neonatal CMV manifestations were significantly more likely than those without to have moderate or severe outcomes (including death) (60%, 36/60, vs 22%, 4/18, p=0.001). 27% of survivors (17/63) had bilateral hearing loss. Conclusions The number of confirmed cases of diagnosed congenital CMV reported in this study was lower than expected, highlighting the need for early and appropriate investigations when congenital infection is suspected. Due to the unexpectedly high proportion of preterm infants, resulting from differential case ascertainment, it was difficult to distinguish prematurity and CMV-related symptoms.

Fertility intentions of HIV-infected women in the United Kingdom

In the United Kingdom (UK), the number of pregnancies in HIV-infected women has increased dramatically over the last decade, but attitudes towards childbearing among infected women have not been previously described. The aim of this survey was to explore fertility intentions among HIV-infected women and to assess the effect of HIV treatment and interventions for prevention of mother-to-child transmission (PMTCT) on these intentions. HIV-infected women, aged between 16 and 49 years, attending one of seven HIV clinics in the UK between July 2003 and January 2004 were asked to complete a questionnaire. Information on demographic factors, HIV test history, pregnancy history and fertility intentions (i.e., desire for children) was collected. Eighty-six per cent of eligible women (450/521) completed the questionnaire. Three quarters of women (336/450) reported that they wanted (more) children. Forty-five per cent (201/450) reported that HIV diagnosis did not affect their fertility intentions, 11% (50/450) that it made them want children sooner, and 10% (44/450) did not know or reported other views. About one third of women (155/450) decided they no longer wanted children after their HIV diagnosis, but 41% of these (59/144) had changed their mind following advances in HIV management and treatment. Factors associated with an increase in fertility intentions after advances in HIV management and treatment were being in a partnership and having fewer than two children. In this survey of HIV-infected women, the majority wanted children and women were more likely to want children after improvements in HIV management and treatment. These findings highlight the need for specialised family planning and reproductive health services targeting this population.

Antiretroviral therapy and congenital abnormalities in infants born to HIV-1-infected women in the United Kingdom and Ireland, 1990 to 2003.

Summary: 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.