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.

The impact of HIV infection and antiretroviral therapy on the predicted risk of Down syndrome.

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.

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.

Risk of triple-class virological failure in children with HIV: a retrospective cohort study.

BACKGROUND: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children. METHODS: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation. FINDINGS: Of 1007 children followed up for a median of 4·2 (IQR 2·4-6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4-14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6-3·0, p<0·0001]). INTERPRETATION: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression. FUNDING: UK Medical Research Council award G0700832.

Using two on-going HIV studies to obtain clinical data from before, during and after pregnancy for HIV-positive women.

BACKGROUND: The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone. RESULTS: Women in UK CHIC receiving HIV-clinical care in 1996-2009, were found in the NSHPC dataset by initially 'linking' records with identical date-of-birth, linked records were then accepted as a genuine 'match', if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively). CONCLUSIONS: Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.

The association between ethnicity and late presentation to antenatal care among pregnant women living with HIV in the UK and Ireland.

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.

The impact of African ethnicity and migration on pregnancy in women living with HIV in the UK: design and methods.

BACKGROUND: The number of reported pregnancies in women with diagnosed HIV in the UK increased from 80 in 1990 to over 1400 in 2010; the majority were among women born in sub-Saharan Africa. There is a paucity of research on how social adversity impacts upon pregnancy in HIV positive women in the UK; furthermore, little is known about important outcomes such as treatment uptake and return for follow-up after pregnancy. The aim of this study was to examine pregnancy in African women living with HIV in the UK. METHODS AND DESIGN: This was a two phase mixed methods study. The first phase involved analysis of data on approximately 12,000 pregnancies occurring between 2000 and 2010 reported to the UK's National Study of HIV in Pregnancy and Childhood (NSHPC). The second phase was based in London and comprised: (i) semi-structured interviews with 23 pregnant African women living with HIV, 4 health care professionals and 2 voluntary sector workers; (ii) approximately 90 hours of ethnographic fieldwork in an HIV charity; and (iii) approximately 40 hours of ethnographic fieldwork in a Pentecostal church. DISCUSSION: We have developed an innovative methodology utilising epidemiological and anthropological methods to explore pregnancy in African women living with HIV in the UK. The data collected in this mixed methods study are currently being analysed and will facilitate the development of appropriate services for this group.

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.

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.

Morbidity, mortality, and response to treatment by children in the United Kingdom and Ireland with perinatally acquired HIV infection during 1996-2006: planning for teenage and adult care.

BACKGROUND: Recent evidence suggests that decreases in morbidity and mortality in cohorts of adults infected with human immunodeficiency virus (HIV) are showing signs of reversal. We describe changes over time in these characteristics and in the response to treatment among children in the United Kingdom and Ireland with perinatally acquired HIV infection, many of whom are now adolescents. METHODS: We analyzed prospective cohort data reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) and the Collaborative HIV Paediatric Study. RESULTS: By mid 2006, 1441 HIV-infected children were reported to NSHPC; 40% were > or = 10 years old at their most recent follow-up visit, and 34% were receiving care outside London. The proportion of children born abroad increased from 24% during 1994-1996 to 64% during 2003-2006. The percentage of total child time during which children received highly active antiretroviral therapy (HAART) increased from 36% during 1997-1999 to 61% during 2000-2002 and 63% during 2003-2006. Of children who were naive to antiretroviral therapy at the start of HAART, the percentage with an HIV-1 RNA load of < 400 copies/mL after 12 months increased from 52% during 1997-1999 to 79% during 2003-2006. In multivariate analysis, only calendar time predicted virological response, whereas both younger age and lower CD4 cell percentage at HAART initiation predicted increases of > 10% in the CD4 cell percentage. A total of 31% of children aged 5-14 years and 38% aged > or = 15 years at their most recent follow-up visit had been exposed to drugs from each of the 3 main HAART classes. The rate of AIDS and mortality combined decreased from 13.3 cases per 100 person-years before 1997 to 3.1 and 2.5 cases per 100 person-years, respectively, during 2000-2002 and 2003-2006; rates of hospital admission also declined during this interval. Of 18 children known to have died since 2003, 9 died within 1 month after presentation. CONCLUSIONS: Morbidity and mortality rates among HIV-infected children continue to decrease over time. Because these children are increasingly dispersed outside London, specialist care is now provided in national clinical networks. Transition pathways to adolescent and adult services and long-term observation to monitor the effects of prolonged exposure to both HIV and HAART are required.

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.

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.

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.

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.

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.

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 12486 singleton pregnancies delivered in 2000-2011 were analyzed. HIV infection status was available for 11515 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.

Influence of short-course antenatal antiretroviral therapy on viral load and mother-to-child transmission in subsequent pregnancies among HIV-infected women.

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.