[Show abstract][Hide abstract] ABSTRACT: 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.
BMC Public Health 09/2014; 14(1):993. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most HIV-positive women on combination antiretroviral therapy (cART) with undetectable HIV viral load now deliver vaginally. Studies from the pre-cART era showed an association between duration of rupture of membranes (ROM) and mother-to-child transmission (MTCT). Here, we investigate the impact of ROM duration on MTCT rates in the cART era.
Archives of Disease in Childhood - Fetal and Neonatal Edition 06/2014; 99(Suppl 1):A4. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze mother-to-child HIV transmission (MTCT) rates over time in light of changes in management, demographic, and pregnancy characteristics.
Population-based surveillance data on diagnosed HIV-positive women and their infants are routinely collected in the UK and Ireland.
A total of 12 486 singleton pregnancies delivered in 2000-2011 were analyzed. HIV infection status was available for 11 515 infants (92.2%).
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.
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.
AIDS (London, England) 02/2014; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 20082010 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: 1.021.16), at least two previous live births (versus none; aPR: 1.22; 95% CI: 1.111.35) and a diagnosis of HIV infection during the first or second trimester (versus before pregnancy; aPR: 1.11; 95% CI: 1.031.20). The overall MTCT rate was 4.1% (95% CI: 3.44.9); 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: 0.160.56). 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.
Bulletin of the World Health Organisation 07/2013; 91(7):491-500. · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Among 396 HIV-infected women conceiving on cART and enrolled in the European Collaborative Study in 2000-11, the proportion with virological failure (>200 copies/ml after ≥24 weeks of treatment) declined substantially from 34% in 2000-01 to 3% in 2010-11. In adjusted analyses, younger women and those with ≥2 children were at increased risk of virological failure, highlighting the importance of close monitoring and adherence support.
AIDS (London, England) 06/2013; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Congenital cytomegalovirus (CMV) is an important cause of neurological problems, particularly sensorineural hearing loss (SNHL), but data on long-term sequelae and the impact of non-primary maternal infection are limited. We report updated findings on childhood outcomes from two large prospective studies.Methods. Pregnant women in Malmö, Sweden, and London, United Kingdom, were included between 1977 and 1986, and newborns 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. 176 congenitally-infected infants were identified among >50,000 screened (Malmö: 76, 4.6/1000; 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 one neonate had neurological symptoms. At follow-up, 7% (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 (p=0.006). All moderate/severe outcomes were identified by age 1; mild sequelae were first identified at 2-5 years in six children, and 6-7 years in three. Among the 16 children with moderate/severe outcomes, two had mothers with confirmed, and seven with presumed non-primary 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. Non-primary infections contributed substantially to the burden of childhood congenital CMV disease.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: HIV-infected women not requiring treatment for their own health usually receive short-course antiretroviral therapy (ART) during pregnancy. Little is known about the effect of this on response to HAART in subsequent pregnancies. METHODS: We analysed data from the UK and Ireland's National Study of HIV in Pregnancy and Childhood for 2000-2010. Analyses were restricted to live births among women not on ART at conception but receiving antenatal HAART. We compared risk of detectable viral load at delivery and mother-to-child transmission in two pregnancy groups: 'ART-naive' and 'HAART-experienced' (≥7 days of HAART during previous pregnancy). Multivariable analyses were conducted using logistic regression. RESULTS: There were 5,372 pregnancies in the ART-naive group and 605 in the HAART-experienced group. Overall, there was weak evidence of an increased risk of detectable viral load in the HAART-experienced group (adjusted odds ratio [aOR] 1.27; 95% CI 1.01, 1.60); however, the increased risk was apparent only among women who previously received non-nucleoside reverse transcriptase inhibitor-based HAART (aOR 1.81; 95% CI 1.25, 2.63), and not among those with previous protease-inhibitor-based HAART exposure (aOR 1.08; 95% CI 0.81, 1.45). There was no difference in mother-to-child transmission risk between the ART-naive and HAART-experienced groups (aOR 0.42; 95% CI 0.10, 1.78), although the number of transmissions was small. CONCLUSIONS: We found no increased risk of detectable viral load at delivery among women exposed to short-course, protease-inhibitor-based HAART during a previous pregnancy. However, women with prior exposure to non-nucleoside reverse transcriptase inhibitor-based HAART appeared to be at increased risk of not adequately suppressing the virus. These findings highlight the need for careful management of HIV-infected women presenting with repeat pregnancies.
[Show abstract][Hide abstract] ABSTRACT: HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.
Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.
Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51-0.75 p<0.01 for 1(st)/2(nd) trimester diagnosis and APR 0.42, 95% CI 0.28-0.63 p<0.01 for 3(rd) trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07-3.11 and APR 3.49 95% CI 2.11-5.76 respectively).
In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.
PLoS ONE 01/2012; 7(4):e34706. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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).
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
AIDS Care 04/2011; 23(9):1093-101. · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the presentation and management of congenital cytomegalovirus (CMV) identified through routine clinical investigations, and ascertain outcome in early childhood.
Active population-based surveillance.
UK and Ireland.
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.
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.
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.
Archives of Disease in Childhood - Fetal and Neonatal Edition 02/2011; 96(6):F398-403. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: To explore the rate of reported congenital abnormalities in infants exposed to antiretroviral therapy in utero.
Comprehensive national surveillance study in the UK and Ireland.
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.
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.
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.
AIDS (London, England) 02/2009; 23(4):519-24. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Comprehensive national surveillance study.
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.
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.
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.
AIDS (London, England) 06/2008; 22(8):973-81. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
National surveillance study.
UK and Ireland.
Diagnosed HIV-infected pregnant women, 1990-2006.
Active surveillance of obstetric and paediatric HIV conducted through the National Study of HIV in Pregnancy and Childhood.
Maternal characteristics, pregnancy outcome, use of antiretroviral therapy, mode of delivery and mother-to-child transmission.
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.
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.
BJOG An International Journal of Obstetrics & Gynaecology 05/2008; 115(9):1078-86. · 3.76 Impact Factor