Stillbirth in Women Living With HIV Delivering in the United Kingdom and Ireland: 2007-2015.

BACKGROUND: Women living with HIV have a higher risk of adverse birth outcomes, but questions remain regarding their specific risk factors for stillbirth and the extent to which maternal HIV is associated with stillbirth. METHODS: Using data on pregnant women with HIV reported within population-based surveillance in the United Kingdom/Ireland, we described stillbirth rates in 2007-2015 stratified by type of antiretroviral therapy (ART) and evaluated risk factors using Poisson regression. General population stillbirth rates by maternal world region of origin were derived from national annual birth statistics, and compared with rates in women with HIV, using standardized stillbirth ratios with the general population as the reference. RESULTS: Between 2007 and 2015, there were 10,434 singleton deliveries in 8090 women with HIV; 75% of pregnancies were in women of African origin; and 49% were conceived on ART. The stillbirth rate was 8.5 (95% confidence interval: 6.9 to 10.5) per 1000 births. Risk factors for stillbirth included pre-eclampsia, diabetes, Asian maternal origin (versus United Kingdom/Ireland), CD4 count <350 cells/mm, older maternal age, and primiparity. Conceiving on ART did not increase the risk. The stillbirth rates (per 1000 births) by type of ART were 14.3, 11.7, 8.3, and 6.0, respectively for NVP + XTC/TDF-, LPV/r + 3TC/ZDV-, NVP + XTC/ABC-, and NVP + XTC/ZDV-exposed pregnancies (P value = 0.40). The standardized stillbirth ratio was 129 (95% confidence interval: 101 to 165) in women with HIV compared with the general population. CONCLUSION: After adjusting for maternal origin, the stillbirth rate remained higher in women with HIV than the general population. We recommend further studies to understand and prevent this excess.

Rubella infection in pregnancy and congenital rubella in United Kingdom, 2003 to 2016.

Rubella vaccination has been included in the United Kingdom's (UK) routine childhood schedule for nearly 30 years. The UK achieved World Health Organization (WHO) elimination status in 2016 and acute rubella infections are rare. In the period 2003-16, 31 rubella infections in pregnancy (0.23 per 100,000 pregnancies) were identified through routine surveillance, of which 26 were in women who were born abroad. Five of the 31 rubella infections led to congenital rubella syndrome in the infant and three had confirmed congenital rubella infection without congenital rubella syndrome. An additional seven babies were identified with congenital rubella syndrome, although rubella infection in pregnancy had not been reported. Place of birth was known for six of these seven mothers, all of whom were born outside the UK, and in five cases maternal infection was acquired abroad. WHO Europe has set targets for measles and rubella elimination and prevention of congenital rubella syndrome by 2015. Vaccination uptake and rubella immunity is high in the UK population and most infections in pregnancy since 2003 were acquired abroad and in unvaccinated women. Every contact with a health professional should be used to check that women are fully immunised according to UK schedule.

Protease inhibitors and preterm delivery: another piece in the puzzle.

BACKGROUND: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir (RTV)-boosted protease inhibitors, timing of ART initiation and immune status. METHODS: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving RTV-boosted protease inhibitor-based (n = 4184) or nonnucleoside reverse transcriptase inhibitors-based regimens (n = 1889). We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4 cell count to minimize bias by indication for treatment and to assess whether PTD risk differs by ART class and specific drug combinations. RESULTS: Among women conceiving on ART, lopinavir/RTV was associated with increased PTD risk in those with CD4 cell count 350 cells/µl or less [odds ratio 1.99 (1.02, 3.85)] and with CD4 cell count more than 350 cells/µl [odds ratio 1.61 (1.07, 2.43)] vs. women on nonnucleoside reverse transcriptase inhibitors-based (mainly efavirenz and nevirapine) regimens in the same CD4 subgroup. Associations between other protease inhibitor-based regimens (mainly atazanavir and darunavir) and PTD risk were complex. Overall, PTD risk was higher in women who conceived on ART, had low CD4 cell count and were older. No trend of association of PTD with tenofovir or any specific drug combinations was observed. CONCLUSION: Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.

Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1.

OBJECTIVE: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. DESIGN: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). METHODS: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. RESULTS: Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). CONCLUSION: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.

Pregnancy incidence and outcomes in women with perinatal HIV infection.

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.

Clinical Status of Adolescents with Perinatal HIV at Transfer to Adult Care in the UK/Ireland.

Background: Increasing numbers of children infected perinatally with human immunodeficiency virus (HIV) are surviving to adolescence and transitioning to adult care, yet there are scarce data on their clinical status at transfer. Methods: We analyzed prospective cohort data from the UK/Ireland national Collaborative HIV Pediatric Study (CHIPS). Clinical status at last pediatric clinic visit prior to transfer was described. Factors associated with higher CD4 cell count and viral load (VL) suppression<400 c/mL among patients on antiretroviral therapy (ART) at transfer were assessed using linear and logistic regression, respectively. Data were matched with the UK HIV Drug Resistance Database (UKHIVDRB) to assess cumulative resistance profiles at transfer. Results: Of 1,907 children followed in CHIPS from 1996 to November 2014, 644 (34%) transferred to adult care: 53% were female, 62% born outside the UK/Ireland, 75% black African. At last pediatric follow-up, median age was 17.4 years [interquartile range 16.5,18.1], 27% had previous AIDS diagnosis, CD4 was 444 cells/mm3 [280, 643], 76% were on ART, 13% off-ART, and 11% ART-naive. Among patients on ART, 74% had VL<400 c/mL. In multivariable analysis, higher CD4 at transfer was associated with younger age, higher CD4 at ART initiation and lower VL at transfer (P ≤ .001). Predictors of viral suppression include no AIDS diagnosis and later year of transfer (P ≤ .05). Of 291 patients with resistance data, 82% had resistance to ≥1 drug class, 56% to ≥2 classes and 12% had triple-class resistance. Conclusion: Three-quarters of adolescents were on stable ART at transfer, of whom 74% were virologically suppressed. The prevalence of triple-class resistance was relatively low at 12%.

Operative vaginal delivery and invasive procedures in pregnancy among women living with HIV.

OBJECTIVES: To describe the use and outcomes of operative delivery and invasive procedures in pregnancy amongst women living with HIV. STUDY DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) is a comprehensive population-based surveillance study in the UK and Ireland. The NSHPC has collected data on operative delivery since 2008, and invasive procedures in pregnancy (amniocentesis, cordocentesis, chorionic villus sampling) from 2012. Descriptive analyses were conducted on 278 pregnancies expected to deliver from 1 January 2008 with outcome reported to the NSHPC by 31 March 2016. RESULTS: Among 9372 pregnancies in 2008-2016, there were 9072 livebirths with 251 operative deliveries and 27 invasive procedures in pregnancy reported. Information was available for 3023/3490 vaginal deliveries, and use of forceps or vacuum reported in 251deliveries (8.2%), increasing over calendar time to almost 10% by 2014-16. Forceps were used twice as often as vacuum delivery, and forceps use increased over time. One infant delivered operatively is known to have acquired HIV. From 2012 there were 4063 pregnancies resulting in 3952 livebirths, 83 terminations and 28 stillbirths. 2163/4063 had information on use (or not) of invasive procedures in pregnancy. Amniocentesis was reported in 25/2163 pregnancies, there was one report of chorionic villus sampling and one of cordocentesis. There were no reported transmissions following invasive procedures in pregnancy. CONCLUSIONS: This is the largest study to date to report on operative delivery in women living with HIV on combined antiretroviral therapy (cART), and provides an up-to-date picture of invasive procedures during pregnancy in this group. Findings from this comprehensive national study are reassuring but numbers are currently low; on-going monitoring is crucial as obstetric care of women with HIV becomes normalised.

Strategies for Monitoring Outcomes in HIV-Exposed Uninfected Children in the United Kingdom.

Surveillance of pregnancies in women living with HIV is carried out on a national basis in the United Kingdom (UK) through the National Study of HIV in Pregnancy and Childhood. There are currently around 1100-1200 HIV-exposed uninfected (HEU) infants born every year in the UK, where vertical transmission of HIV now occurs in fewer than 5 in every 1000 pregnancies. By the end of 2014, there was a cumulative total of more than 15,000 HEU children with any combination antiretroviral therapy (cART) exposure and more than 5000 with cART exposure from conception in the UK. HEU infants are increasingly being exposed to newer antiretroviral drugs for which less is known regarding both short- and long-term safety. In this commentary, we describe the approaches that have been taken to explore health outcomes in HEU children born in the UK. This includes the Children exposed to AntiRetroviral Therapy (CHART) Study, which was a consented follow-up study carried out in 2002-2005 of HEU children born in 1996-2004. The CHART Study showed that 4% of HEU children enrolled had a major health or development problem in early childhood; this was within expected UK norms, but the study was limited by small numbers and short-term follow-up. However, the problems with recruitment and retention that were encountered within the CHART Study demonstrated that comprehensive, clinic-based follow-up was not a feasible approach for long-term assessment of HEU children in the UK. We describe an alternative approach developed to monitor some aspects of their long-term health, involving the "flagging" of HEU infants for death and cancer registration with the UK Office for National Statistics. Some of the ethical concerns regarding investigation of long-term outcomes of in utero and perinatal exposure to antiretrovirals, including those relating to consent and confidentiality, are also discussed.

Loss to Follow-Up After Pregnancy Among Sub-Saharan Africa-Born Women Living With Human Immunodeficiency Virus in England, Wales and Northern Ireland: Results From a Large National Cohort.

BACKGROUND: Little is known about retention in human immunodeficiency virus (HIV) care in HIV-positive women after pregnancy in the United Kingdom. We explored the association between loss to follow-up (LTFU) in the year after pregnancy, maternal place of birth and duration of UK residence, in HIV-positive women in England, Wales, and Northern Ireland. METHODS: We analyzed combined data from 2 national data sets: the National Study of HIV in Pregnancy and Childhood; and the Survey of Prevalent HIV Infections Diagnosed, including pregnancies in 2000 to 2009 in women with diagnosed HIV. Logistic regression models were fitted with robust standard errors to estimate adjusted odds ratios (AOR). RESULTS: Overall, 902 of 7211 (12.5%) women did not access HIV care in the year after pregnancy. Factors associated with LTFU included younger age, last CD4 in pregnancy of 350 cells/µL or greater and detectable HIV viral load at the end of pregnancy (all P<0.001). On multivariable analysis, LTFU was more likely in sub-Saharan Africa-born (SSA-born) women than white UK-born women (AOR, 2.17; 95% confidence interval, 1.50-3.14; P<0.001). The SSA-born women who had migrated to the UK during pregnancy were 3 times more likely than white UK-born women to be lost to follow-up (AOR, 3.19; 95% confidence interval, 1.94-3.23; P<0.001). CONCLUSIONS: One in 8 HIV-positive women in England, Wales, and Northern Ireland did not return for HIV care in the year after pregnancy, with SSA-born women, especially those who migrated to the United Kingdom during pregnancy, at increased risk. Although emigration is a possible explanatory factor, disengagement from care may also play a role.

Maternal and foetal outcomes among 4118 women with HIV infection treated with lopinavir/ritonavir during pregnancy: analysis of population-based surveillance data from the national study of HIV in pregnancy and childhood in the United Kingdom and Ireland.

BACKGROUND: The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts comprehensive population-based surveillance of pregnancies in women with HIV infection in the United Kingdom/Ireland. Use of antepartum antiretroviral therapy (ART) for prevention of mother-to-child transmission (MTCT) and to treat maternal infection, if required, is standard practise in this population; lopinavir/ritonavir (LPV/r) is commonly used. The study objective was to examine the use of LPV/r among pregnant women with HIV infection to describe maternal and foetal outcomes. METHODS: The NSHPC study collected maternal, perinatal and paediatric data through confidential and voluntary obstetric and paediatric reporting schemes. Pregnancies reported to the NSHPC by June 2013, due to deliver 2003-2012 and with LPV/r exposure were included in this analysis, using pregnancy as the unit of observation. RESULTS: Four thousand eight hundred sixty-four LPV/r-exposed pregnancies resulting in 4702 deliveries in 4118 women were identified. Maternal region of birth was primarily sub-Saharan Africa (77 %) or United Kingdom/Ireland (14 %). Median maternal age at conception was 30 years. LPV/r was initiated preconception in 980 (20 %) and postconception in 3884 (80 %) pregnancies; median duration of antepartum LPV/r exposure was 270 and 107 days, respectively. Viral load close to delivery was <50 copies/mL in 73 % and <1000 copies/mL in 94 % of women. 63 % of deliveries were by caesarean section (elective, 6 %; emergency, 38 %). Among singleton live births, 13 % were <37 weeks of gestation (2.5 % <32 weeks) and 15 % had birth weight <2500 g (2.3 % <1500 g). MTCT rates were 1.1 (2003-2007) and 0.5 % (2008-2012). 134 live born children (2.9 %) had ≥1 congenital abnormality. CONCLUSIONS: The results of this analysis using real-world data from a large number of pregnant women with HIV infection in the United Kingdom and Ireland who received LPV/r-containing ART regimens demonstrate that these regimens have a good safety profile and are effective for viral suppression during pregnancy, with associated low rates of MTCT.

"It pains me because as a woman you have to breastfeed your baby": decision-making about infant feeding among African women living with HIV in the UK.

OBJECTIVES: UK guidance advises HIV-positive women to abstain from breast feeding. Although this eliminates the risk of postnatal vertical transmission of HIV, the impact of replacement feeding on mothers is often overlooked. This qualitative study examines, for the first time in the UK, decision-making about infant feeding among African women living with HIV. METHODS: Between 2010 and 2011, we conducted semistructured interviews with 23 HIV-positive African women who were pregnant or had recently given birth. We recruited participants from three HIV antenatal clinics in London. RESULTS: Women highlighted the cultural importance of breast feeding in African communities and the social pressure to breast feed, also describing fears that replacement feeding would signify their HIV status. Participants had significant concerns about physical and psychological effects of replacement feeding on their child and felt their identity as good mothers was compromised by not breast feeding. However, almost all chose to refrain from breast feeding, driven by the desire to minimise vertical transmission risk. Participants' resilience was strengthened by financial assistance with replacement feeding, examples of healthy formula-fed children and support from partners, family, peers and professionals. CONCLUSIONS: The decision to avoid breast feeding came at considerable emotional cost to participants. Professionals should be aware of the difficulties encountered by HIV-positive women in refraining from breast feeding, especially those from migrant African communities where breast feeding is culturally normative. Appropriate financial and emotional support increases women's capacity to adhere to their infant-feeding decisions and may reduce the emotional impact.

The risk of viral rebound in the year after delivery in women remaining on antiretroviral therapy.

OBJECTIVE: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART). METHODS: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50 copies/ml or less at delivery in 2006-2011, who started life-long cART during pregnancy (n = 321) or conceived on cART (n = 618), were matched by age, duration on cART and time period, with at least one control (non-postpartum). The cumulative probability of viral rebound (HIV-RNA >200 copies/ml) was assessed by Kaplan-Meier analysis; adjusted hazard ratios (aHRs) for the 0-3 and 3-12 months postdelivery (cases)/pseudo-delivery (controls) were calculated in Cox proportional hazards models. RESULTS: In postpartum women who conceived on cART, 5.9% [95% confidence interval (95% CI) 4.0-7.7] experienced viral rebound by 3 months, and 2.2% (1.4-3.0%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during the first 3 months [aHR 2.63 (1.58-4.39)] but not during the 3-12 months postdelivery/pseudo-delivery. In postpartum women who started cART during pregnancy, 27% (22-32%) experienced viral rebound by 3 months, and 3.0% (1.6-4.4%) of their controls. The risk of viral rebound was higher in postpartum women than in controls during both postdelivery/pseudo-delivery periods [<3 months: aHR 6.63 (3.58-12.29); 3-12 months: aHR 4.05 (2.03-8.09)]. CONCLUSION: In women on suppressive cART, the risk of viral rebound is increased following delivery, especially in the first 3 months, which may be related to reduced adherence, indicating the need for additional adherence support for postpartum women.

Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

OBJECTIVE: The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). DESIGN: Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). METHODS: Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4). Women starting ART in 2000-2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4 cell count, drug regimen and hepatitis B virus/hepatitis C virus (HBV/HCV) coinfection. RESULTS: One-quarter (25.7%, 982/3815) of women were pregnant during follow-up, 14.2% (n = 541) when starting ART. The rate of LEE was 14.5/100 person-years in and 6.0/100 person-years outside of pregnancy. The rate of severe LEE was 3.9/100 person-years in and 0.6/100 person-years outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy [LEE: adjusted hazard ratio (aHR) 1.66 (1.31-2.09); severe LEE: aHR 3.57 (2.30-5.54)], including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4 cell count (<250 cells/µl), HBV/HCV coinfection and calendar year. CONCLUSION: Although few women developed severe LEE, this study provides further evidence that pregnancy is associated with an increased risk of LEE and severe LEE, reinforcing the need for regular monitoring of liver biomarkers during pregnancy.

Does pregnancy increase the risk of ART-induced hepatotoxicity among HIV-positive women?

INTRODUCTION: High 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 METHODS: Combined 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. RESULTS: Of 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/mm(3) vs. 251-350 cells/mm(3) 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). CONCLUSIONS: Pregnant women were at increased risk of LEE, highlighting the importance of close monitoring of toxicity biomarkers during pregnancy.

Outcomes related to 4864 pregnancies with exposure to lopinavir/ritonavir (LPV/r).

INTRODUCTION: During 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: In 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.

Long-term virological outcome in children on antiretroviral therapy in the UK and Ireland.

OBJECTIVE: To assess factors at the start of antiretroviral therapy (ART) associated with long-term virological response in children. DESIGN: Multicentre national cohort. METHODS: Factors associated with viral load below 400 copies/ml by 12 months and virologic failure among children starting 3/4-drug ART in the UK/Irish Collaborative HIV Paediatric Study were assessed using Poisson models. RESULTS: Nine hundred and ninety-seven children started ART at a median age of 7.7 years (inter-quartile range 2.9­11.7), 251 (25%) below 3 years: 411 (41%) with efavirenz and two nucleoside reverse transcriptase inhibitors (EFVþ2NRTIs), 264 (26%) with nevirapine and two NRTIs (NVPþ2NRTIs), 119 (12%; 106 NVP, 13 EFV) with non-nucleoside reverse transcriptase inhibitor and three NRTIs (NNRTIþ3NRTIs), and 203 (20%) with boosted protease inhibitor-based regimens. Median follow-up after ART initiation was 5.7 (3.0­8.8) years. Viral load was less than 400 copies/ml by 12 months in 92% [95% confidence interval (CI) 91­94%] of the children. Time to suppression was similar across regimens (P»0.10), but faster over calendar time, with older age and lower baseline viral load. Three hundred and thirtynine (34%) children experienced virological failure. Although progression to failure varied by regimen (P<0.001) and was fastest for NVPþ2NRTIs regimens, risk after 2 years on therapy was similar for EFVþ2NRTIs and NVPþ2NRTIs, and lowest for NNRTIþ3NRTIs regimens (P-interaction»0.03). Older age, earlier calendar periods and maternal ART exposure were associated with increased failure risk. Early treatment discontinuation for toxicity occurred more frequently for NVP-based regimens, but 5-year cumulative incidence was similar: 6.1% (95% CI 3.9­8.9%) NVP, 8.3% (95% CI 5.6­11.6) EFV, and 9.8% (95% CI 5.7­15.3%) protease inhibitor-based regimens (P»0.48). CONCLUSION: Viral load suppression by 12 months was high with all regimens. NVPþ3NRTIs regimens were particularly efficacious in the longer term and may be a good alternative to protease inhibitor-based ART in young children.

Pregnancy outcomes in women growing up with perinatally acquired HIV in the United Kingdom and Ireland.

INTRODUCTION: In 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. METHODS: Pregnancies 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. RESULTS: A 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. CONCLUSIONS: Currently 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.

Immunologic status and virologic outcomes in repeat pregnancies to HIV-positive women not on antiretroviral therapy at conception: a case for lifelong antiretroviral therapy?

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.