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To perform laboratory static validation of pressures from an innovative, single-sensor pressure and temperature monitoring device for the early detection of complications in the high-risk foot. Can an innovative, newly developed, in-shoe pressure and temperature measuring device, detect and measure the in-shoe peak plantar pressures and skin temperature as accurately as the reference standard? A pressure generating rig, the Tekscan™ Equilibration 'bladder calibrator', was used to produce a known force, against the gold standard, FScan™ in-shoe pressure mapping system by Tekscan™ and a newly developed prototype. The F-scan® system was used to record the pressure readings and establish a baseline for the readings recorded utilising the prototype. A total of 20 pressure values were recorded with 100 samples each. Exploratory data analysis was conducted to gain insights and analyse the prototype's behaviour at different pressure points. Pre-processing and data cleaning were also performed to remove any anomalies. Support Vector Regressor with a polynomial kernel and Grid-Search algorithm was used to fit the recorded data curve. The best combination of parameters had a Mean Squared Error of 2.59 and a Root Mean Squared Error of 1.61. A simple linear equation was used to convert raw readings to pressure values. The results of this study conclude that the pressure measurements taken with the prototype are congruent to the gold standard, F-scan® in-shoe system. This confirms that the prototype is a valid device that can be used safely as a low-cost alternative to current costly commercial in-shoe pressure mapping devices. • Confirmed validity of the innovative in-shoe pressure and temperature device. • Prototype effective in reading pressure as the reference standard. • Can be safely used in to monitor the high-risk foot. [ABSTRACT FROM AUTHOR]

Available technology to detect the 2 primary predictors of ulceration is not being used as it is deemed as costly and time-consuming. Thus, the aim of this study was to determine dynamic laboratory validation, of an innovative, single-sensor in-shoe device that can read peak pressure and temperature simultaneously. Can an innovative, newly developed, in-shoe pressure and temperature measuring device, detect and measure the in-shoe peak plantar pressures and skin temperature of healthy participants, as accurately as the reference standard? Five healthy adult participants were recruited. The prototype was validated against the gold standard FScan™ in-shoe system for pressures and the Flir® T630sc thermographic camera for temperatures. Participants were asked to walk at a comfortable pace on an electric treadmill for 13 min. The prototype and the FScan in-shoe sensors™ were superimposed inside the shoe of the participant, with the prototype on top, to ensure direct contact with the area of interest. Two thermographic images were captured using the Flir® T630sc thermographic camera, before and after the walk. During the trials, the participants wore 100 % cotton socks and their own sports shoes and pressures were recorded at 50 readings a second. The raw readings of pressure were passed to the regressor, which returned the estimated kPa value. Several evaluations metrics were used to evaluate the performance of the modal. The prototype gave equal results to that of the gold standard, the FScan™ in-shoe system. With regards to temperature measurements, both devices gave similar readings. This innovative single-sensor, in-shoe pressure and temperature monitoring device showed similar measurements of pressure to the FScan™ system and temperature measurements were equivalent to the Flir® T630sc thermographic camera. The authors are confident that the innovative, low cost, single-sensor, in-shoe pressure and temperature monitoring device can be used as an alternative to the costly available commercial devices that measure pressure and temperature separately to detect early signs of complications in the high-risk foot. • Confirmed validity of the innovative in-shoe pressure and temperature device. • Prototype effective in reading pressure as the reference standard. • Highlighted a correlation between increase in pressure and temperature. • Can be safely used in to monitor the high-risk foot. [ABSTRACT FROM AUTHOR]

Background: Early infant HIV diagnosis (EID) is critical to ensuring timely diagnosis of HIV-exposed infants, and treatment in those found to be infected. However estimates of coverage vary considerably, depending on data sources used. We used 4 methods to estimate coverage among a historical cohort of HIV-exposed infants in rural South Africa, between 2010–2016. Methods: We estimated the proportion of infants ever tested (methods 1–3) and tested by 7 weeks of age (1–4) as follows: (1) infants born to women identified as HIV-positive in demographic surveillance were linked to those with ≥1 EID result in routine laboratory surveillance; (2) the number of infants with ≥1 EID result in laboratory surveillance divided by the estimated number of HIV-exposed infants, calculated as total live births multiplied by antenatal HIV seroprevalence; (3) the number of infants with ≥1 EID result in routine laboratory surveillance, divided by the number of HIV-exposed infants as estimated by the district health service; (4) from documentation in infants' Road-to-Health-booklets. Results: The proportion ever tested was 43%, 88% and 138% for methods 1–3, and by 7 weeks of age was 25%, 49%, 86% and 46% for methods 1–4 respectively. Conclusions: The four methods, applied to a range of routine data sources, resulted in estimates varying considerably, and the true coverage of EID remains unclear. Our findings highlight the importance of developing unique patient identifiers, improving training of healthcare providers using reporting systems, and ensuring the accuracy of healthcare records, to ensure the best possible health outcomes for HIV-exposed infants. [ABSTRACT FROM AUTHOR]

Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015-16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate whether there are any significant differences in muscle activity between individuals living with type II diabetes mellitus (T2DM) and individuals living with T2DM and peripheral arterial disease (PAD), during gait at a self-selected speed. The influence of different stages of PAD on muscle activity during gait was also assessed with the use of surface electromyography (EMG).Research Question: Does PAD affect lower limb muscle activity during gait in the presence of T2DM?Methods: This quantitative study involves a prospective, comparative, non-experimental subject design. Ninety participants were divided into three groups namely Group A (thirty participants living with T2DM), Group B(i) (thirty participants living with T2DM and mild PAD) and Group B(ii) (thirty participants living with T2DM and severe PAD). Surface electrode sensors were placed according to SENIAM guidelines, on six main lower limb muscles on both limbs. Muscle activity was recorded using a wireless system, where participants were instructed to walk at a self-selected speed on a 10-m walkway. Average Burst RMS was performed and the amplitude (mV) and the duration of muscle activation (s) was analysed.Results: There was a significant increase in muscle amplitude and duration of activation in the presence of lower limb ischaemia during gait. The largest significant difference (p = <0.05) in EMG amplitude and duration of activation when looking at the twelve muscles in general was found between participants living with T2DM and participants living with T2DM and severe PAD.Significance: The increase in muscle activity indicates that there are musculoskeletal and biomechanical changes in the lower limb musculature with increasing severity of PAD. Higher muscle exertion demands are required during gait which may result in earlier fatigue. EMG tests would be beneficial for detecting muscle dysfunction objectively and non-invasively in T2DM and PAD. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Birth outcome data with dolutegravir exposure during pregnancy, particularly in the first trimester, are needed. Setting: Data were prospectively collected from the Antiretroviral Pregnancy Registry and European Pregnancy and Paediatric HIV Cohort Collaboration. Methods: We reviewed 2 large, independent antiretroviral pregnancy registries to assess birth outcomes associated with maternal dolutegravir treatment during pregnancy. Results: Of 265 pregnancies reported to the Antiretroviral Pregnancy Registry, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure. Of 101 pregnancies reported to the European Pregnancy and Paediatric HIV Cohort Collaboration, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births, respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first-trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester. Conclusions: Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive because of small sample sizes. [ABSTRACT FROM AUTHOR]

Objectives: Increasingly more women conceive on antiretroviral therapy (ART) with non-nucleoside reverse transcriptase-based regimens. This study assessed the effect of preconception tenofovir disoproxil fumarate (TDF)-lamivudine (3TC)/emtricitabine (FTC)-efavirenz (EFV) and post-conception TDF-(3TC/FTC)-EFV (versus other regimens) on preterm delivery (PTD) and small-for-gestational age (SGA) births. Methods: We analysed data of 2549 HIV-infected women attending antenatal clinics in KwaZulu-Natal from 2010 through 2015 in this retrospective cohort study. Preconception, TDF-(3TC/FTC)-EFV was compared to nevirapine (NVP)-based regimens and other 3-drug EFV-based regimens. Post-conception, TDF-(3TC/FTC)-EFV was compared to NVP-based ART and zidovudine (ZDV) prophylaxis. Outcomes included PTD <37 weeks and SGA births. Generalized linear mixed effects were used to fit logistic regression models to account for repeat pregnancies. Results: Among 2549 singleton live births, 10.4% (n = 264) were PTD and 10.4% (n = 265) SGA. PTD declined from 16.3% in 2010 to 9.3% in 2015 and SGA remained stable from 9.9% in 2010 to 10% in 2015. Preconception NVP-based regimens [adjusted odds ratio (aOR) 0.66; 95% CI 0.27–1.63] and other 3-drug EFV-based regimens (aOR 0.72; 95% CI 0.24–2.12) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based (aOR 0.75; 95% CI 0.40–1.42) and other 3-drug EFV-based regimens (aOR 1.55; 95% CI 0.76–3.16) were not associated with SGA births versus TDF-(3TC/FTC)-EFV. Post-conception NVP-based ART (1.77; 95% CI 0.89–3.51) and ZDV (1.03; 95% CI 0.68–1.58) were not associated with PTD versus TDF-(3TC/FTC)-EFV. NVP-based ART (1.55; 95% CI 0.66–3.61) and ZDV (0.89; 95% CI 0.53–1.47) were not associated with SGA versus TDF-(3TC/FTC)-EFV. Conclusions: Preconception TDF-(3TC/FTC)-EFV and post-conception TDF-(3TC/FTC)-EFV were not associated with PTD or SGA, compared with other regimens. Increasing ART use merits further study of the optimum ART regimen for safe birth outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIVpositive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Methods Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. Results In adjusted analyses, ART-naïve (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. Conclusions In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman's health. [ABSTRACT FROM AUTHOR]

Introduction: 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 HIVpositive women in Ukraine, which has the most severe HIV epidemic in Europe. Methods: 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. Results: 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 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28-0.63 p<0.01 for 3rd 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims To compare clinical status, mother-to-child transmission (MTCT) rates, use of prevention of (PMTCT) interventions and pregnancy outcomes between HIV-infected injecting drug users (IDUs) and non-IDUs. Design and setting Prospective cohort study conducted in seven human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Centres in Ukraine, 2000-10. Participants Pregnant HIV-infected women, identified before/during pregnancy or intrapartum, and their live-born infants ( n = 6200); 1028 women followed post-partum. Measurements Maternal and delivery characteristics, PMTCT prophylaxis, MTCT rates, preterm delivery (PTD) and low birth weight (LBW). Findings Of 6200 women, 1111 (18%) reported current/previous IDU. The proportion of IDUs diagnosed with HIV before conception increased from 31% in 2000/01 to 60% in 2008/09 ( P < 0.01). Among women with undiagnosed HIV at conception, 20% of IDUs were diagnosed intrapartum versus 4% of non-IDUs ( P < 0.01). At enrolment, 14% of IDUs had severe/advanced HIV symptoms versus 6% of non-IDUs ( P < 0.001). IDUs had higher rates of PTD and LBW infants than non-IDUs, respectively, 16% versus 7% and 22% versus 10% ( P < 0.001). IDUs were more likely to receive no neonatal or intrapartum PMTCT prophylaxis compared with non-IDUs (OR 2.81, p < 0.001). MTCT rates were 10.8% in IDUs versus 5.9% in non-IDUs; IDUs had increased MTCT risk (adjusted odds ratio 1.32, P = 0.049). Fewer IDUs with treatment indications received HAART compared with non-IDUs (58% versus 68%, P = 0.03). Conclusions Pregnant human immunodeficiency virus-infected injecting drug users in Ukraine have worse clinical status, poorer access to prevention of mother-to-child transmission prophylaxis and highly active antiretroviral therapy, more adverse pregnancy outcomes and higher risk of mother-to-child transmission than non-injecting drug user women. [ABSTRACT FROM AUTHOR]

Summary: The HIV epidemic in central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) has accelerated since 2000. This expansion in the epidemic is largely attributable to escalating injection drug use, reflecting central Asia''s geographic position along major drug trafficking routes. Although up to 75% of cumulative HIV cases have been among injection drug users (IDUs) so far, HIV infections are increasing in other population groups, including female sex workers and their clients, prisoners, and migrants. Among IDUs, risky injecting practices are highly prevalent, and the intersecting epidemic of sexually transmitted infections, particularly syphilis, highlights the potential for sexual transmission of HIV to bridging populations. Few HIV cases in children have been reported so far, with most resulting from nosocomial outbreaks in hospital settings. Some recent progress has been made towards scaling-up prevention, treatment, and care services, including harm reduction for IDUs, although key challenges remain. [Copyright &y& Elsevier]

A letter to the editor is presented about the use of neonatal antiretroviral prophylaxis for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV).

Background: Ukraine was the epicentre of the HIV epidemic in Eastern Europe, which has the most rapidly accelerating HIV epidemic world-wide today; national HIV prevalence is currently estimated at 1.6%. Our objective was to evaluate the uptake and effectiveness of interventions for prevention of mother-to-child transmission (PMTCT) over an eight year period within operational settings in Ukraine, within the context of an ongoing birth cohort study. Methods: The European Collaborative Study (ECS) is an ongoing birth cohort study in which HIV-infected pregnant women identified before or during pregnancy or at delivery were enrolled and their infants prospectively followed. Three centres in Ukraine started enrolling in 2000, with a further three joining in September 2006. Results: Of the 3356 women enrolled, 21% (689) reported current or past injecting drug use (IDU). Most women were diagnosed antenatally and of those, the proportion diagnosed in the first/ second trimester increased from 47% in 2000/01 (83/178) to 73% (776/1060) in 2006/07 (p < 0.001); intrapartum diagnosis was associated with IDU (Adjusted odds ratio 4.38; 95%CI 3.19-6.02). The percentage of women not receiving any antiretroviral prophylaxis declined from 18% (36/205) in 2001 to 7% in 2007 (61/843) (p < 0.001). Use of sdNVP alone substantially declined after 2003, with a concomitant increase in zidovudine prophylaxis. Median antenatal zidovudine prophylaxis duration increased from 24 to 72 days between 2000 and 2007. Elective caesarean section (CS) rates were relatively stable over time and 34% overall. Mother-to-child transmission (MTCT) rates decreased from 15.2% in 2001 (95%CI 10.2-21.4) to 7.0% in 2006 (95%CI 2.6-14.6). In adjusted analysis, MTCT risk was reduced by 43% with elective CS versus vaginal delivery and by 75% with zidovudine versus no prophylaxis. Conclusion: There have been substantial improvements in use of PMTCT interventions in Ukraine, including earlier diagnosis of HIV-infected pregnant women and increasing coverage with antiretroviral prophylaxis and the initial MTCT rate has more than halved. Future research should focus on hard-to-reach populations such as IDU and on missed opportunities for further reducing the MTCT rate. [ABSTRACT FROM AUTHOR]

Antiretroviral drugs have been used routinely to reduce the risk of mother-to-child transmission of HIV infection since 1994, following the AIDS Clinical Trials Group 076 trial, which demonstrated the efficacy of zidovudine in reducing the risk of in utero and intrapartum transmission. The use of antiretroviral drugs in pregnancy varies geographically, with widespread use of highly active antiretroviral therapy (HAART) in resource-rich settings for delaying maternal HIV disease progression as well as the prevention of mother-to-child transmission; however, in low-and middle-income settings, abbreviated prophylactic regimens focus on the perinatal period, with very limited access to HAART to date. The potential risks associated with antiretroviral exposure for pregnant women, fetuses and infants depend on the duration of this exposure as well as the number and type of drugs. As the benefits of HAART regimens in reducing the risk of mother-to-child transmission and in delaying disease progression are so great, their widespread use has been accepted, despite the relative lack of safety data from human pregnancies. Animal studies have suggested an increased risk of malformations associated with exposure to specific antiretroviral drugs, although evidence to support this from human studies is limited. Trials, cohorts and surveillance studies have shown no evidence of an increased risk of congenital malformations associated with in utero exposure to zidovudine, or other commonly used antiretroviral drugs, with an estimated 2-3% prevalence of birth defects (i.e. similar to that seen in the general population). Exposure to prophylactic zidovudine for prevention of mother-to-child transmission is associated with a usually mild and reversible, but rarely severe, anaemia in infants. However, a medium-term impact on haematological parameters of antiretroviral-exposed infants has been reported, with small but persistent reductions in levels of neutrophils, platelets and lymphocytes in children up to 8 years of age; the clinical significance of this remains uncertain. To date, there is no evidence to suggest that exposure to antiretroviral drugs in utero or neonatally is associated with an increased risk of childhood cancer, but the potential for mutagenic and carcinogenic effects at older ages cannot be excluded. Nucleoside analogue-related mitochondrial toxicity is well recognised from studies in non-pregnant individuals, whilst animal studies have provided evidence of mitochondrial toxicity resulting from in utero antiretroviral exposure. Clinically evident mitochondrial disease in children with antiretroviral exposure has only been described in Europe, with an estimated 18-month incidence of ‘established‘ mitochondrial dysfunction of 0.26% among exposed children. Regarding pregnancy-related adverse effects, increased risks of prematurity, pre-eclampsia and gestational diabetes mellitus have been reported by a variety of observational studies with varying strengths of evidence and with conflicting results. Based on current knowledge, the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects. However, these potential adverse effects require further and longer term monitoring because they are likely to be rare and to occur later in childhood. [ABSTRACT FROM AUTHOR]

Summary: Both HIV and hepatitis C virus (HCV) can be transmitted from mother to child during pregnancy and delivery. Vertical transmission of HIV and HCV separately is most likely from HIV/HCV-coinfected mothers; however, transmission of both infections is less frequent. The effect of HCV coinfection on HIV-related disease remains unclear; whereas most studies indicate no effect, recent results suggest HCV in adults accelerates HIV progression. Little is known about how HIV coinfection affects HCV progression in children and the information available is based on small numbers of patients. Paediatric HIV treatment is extremely successful and it is vital to determine if HCV coinfection alters the effectiveness of this treatment. The hepatotoxicity of many HIV therapies and the possible negative impact of HCV on this treatment, alongside the interactions and contraindications of many HIV and HCV therapies, further limits the choice of paediatric treatments for coinfected children. Future research must therefore focus on vertically acquired HIV/HCV coinfection to inform treatment trials addressing coinfection management. [Copyright &y& Elsevier]

To examine how the subsequent childbearing of HIV-infected mothers enrolled in the European Collaborative Study (ECS) has changed over time and identify factors predictive of further childbearing. Prospective cohort study. Centres in nine European countries included in the ECS, enrolled between end 1986 and November 2003. HIV-infected women (3911): 3693 with only one and 218 with subsequent live births. Univariable and multivariable logistic regression analyses to obtain odds ratios (OR) and 95% confidence intervals (CI). Kaplan–Meier (KM) analyses to estimate cumulative proportions of women having a subsequent live birth. Subsequent live birth. In multivariable analysis adjusting for time period, ethnicity, maternal age and parity, black women were more likely [adjusted odds ratio (AOR) 2.45; 95% CI, 1.75–3.43], and women>30 years less likely (AOR 0.54, 0.37–0.80), to have a subsequent live birth. Time to subsequent live birth significantly shortened over time, with an estimated 2% of women having a subsequent live birth within 24 months of enrolment pre-1989 versus 14% in 2000–2003 ( P< 0.001). Estimated time to subsequent live birth was shorter for black than for white women ( P< 0.001). The likelihood of subsequent live births substantially increased after 1995 and birth intervals were shorter in women on HAART and among black women. Numbers are currently too small to address the issue of advantages and disadvantages in the management of subsequent deliveries. [ABSTRACT FROM AUTHOR]

Background. Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. Methods. Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. Results. Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P = .003) and elective Caesarean section (AOR, 0.33; P = .04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. Conclusions. Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important. [ABSTRACT FROM AUTHOR]

Describes the characteristics of children infected vertically with HIV surviving ten years or more who were enrolled in the prospective European Collaborative Study. Discussion on pediatric HIV infection; Clinical, immunologic and virologic status of HIV patients; Antiretroviral therapy in children; Need for health education for HIV-infected adolescents.

Background: In diabetic foot ulceration, a correlation between pressure and skin temperature is suspected. The aim of this systematic review is to provide a more rigorous analysis of existing literature related to the various technologies used to read and measure both in-shoe plantar pressures, and in-shoe skin temperatures simultaneously.Methods: A systematic review of the literature related to the topic was searched in database sources such as Medline OVID, Cochrane Library, PubMed, CONAHL, PROSPERO, and Elsevier. Outcome measures of interest included validity, reliability and responsiveness of in-shoe temperature and/or pressure mapping device used, and characteristics and quantity of sensors used, anatomical landmarks and statistical analysis used to interpret the data. Quality of evidence and risk of bias was evaluated using the QUADAS-2.Results: Nineteen studies were identified and included in this review. The majority of studies used a small sample size (mean n = 17) and recruited healthy participants. All studies have shown excellent validity but only a few tested for the reliability of the device. None of the studies tested for responsiveness of the device. Quality assessment results scored high risk in view of 'patient selection', 'use of reference standard' and 'applicability', and low risk in view of 'use if index test' and 'flow and timing'.Conclusions: The data outlined in this review confirms that further improvement, reliability testing and clinical validation of the developed systems is required despite the results of excellent performance in detecting changes of in-shoe skin temperature and pressure. [ABSTRACT FROM AUTHOR]

Presents a study that examined services available for families with HIV infection in Europe and their satisfaction with said services. Details of a survey on clinical and psychosocial services; Similarity of the range of services provided; General satisfaction with clinic organization; Satisfactory level of provided information; Information on unmet service needs.

The author reflects on various issues associated with preterm delivery in women suffering from human immunodeficiency virus (HIV) infection. Mother-to-child transmission is a major source of HIV transmission in children which can be significantly reduced through the widespread usage of combination antiretroviral therapy (ART). He also discusses a study conducted by Jeanne Sibiude from the French Perinatal Cohort concerned with the efficacy of ART in HIV-positive pregnant women.

The antenatal prevalence of HIV/HCV coinfection ranges from 12% to 28% with mother-to-child transmission rates ranging from 3.6% to 9.5%. There are no guidelines detailing the most appropriate clinical management and treatment of coinfected children. We used a semi-structured questionnaire to investigate current European practices for the management and follow-up of HIV/HCV coinfected children among clinical centres contributing to the European Collaborative Study or the European Paediatric HCV Network. Clinicians from 16 out of 24 clinical centres responded and were caring for a total of 44 HIV/HCV coinfected children. We found that, although there was a high level of concordance regarding testing for HIV and/or HCV infection, monitoring practices in these European centres varied widely. Few clinicians stated they would administer HIV and HCV treatment concurrently. Limited experience in the clinical management of this group and the lack of an evidence base to guide policy may be a barrier to achieving optimal care and treatment. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor referencing articles and topics on the side effects of highly active antiretroviral therapy to pregnant women, published in previous issues.

Introduction Methods Results Conclusions The extent to which individuals living with HIV experience residential and healthcare mobility during pregnancy in the UK is unknown. We aimed to determine a minimum estimate of residential and healthcare mobility during pregnancy in people living with HIV in the UK in 2009–2019 to explore patterns of and factors associated with mobility and to assess whether mobility was associated with specific HIV outcomes.We analyzed data from the Integrated Screening Outcomes Surveillance Service to assess pregnancies with HIV in the UK and included livebirths and stillbirths with estimated delivery in 2009–2019. Residential mobility was defined as changing residential postcode between notification and delivery, and healthcare mobility was defined as changing NHS Trust or Strategic Health Authority (SHA) in that same timeframe. We used logistic regression to determine factors associated with residential and healthcare mobility and with detectable delivery viral load.Among 10 305 pregnancies, 19.6% experienced residential mobility, 8.1% changed NHS Trust, and 4.5% changed SHA during pregnancy. Mobility was more likely to be experienced by younger women, migrants, and those with new antenatal diagnosis; residential but not healthcare mobility declined over time. In a fully adjusted model, mobility was not associated with having a detectable viral load at delivery. Higher proportions of infants were lost to follow‐up after mobile pregnancies than after non‐mobile pregnancies.This analysis provides new knowledge on mobility during pregnancy in the context of HIV, but further research is needed to understand its broader impacts and its utility as a marker to help identify families requiring additional follow‐up and support. [ABSTRACT FROM AUTHOR]

Congenital syphilis is a major global cause of fetal loss, stillbirth, neonatal death, and congenital infection. In 2020, the global rate of congenital syphilis was 425 cases per 100 000 livebirths—substantially higher than WHO's elimination target of 50 cases per 100 000 livebirths. Case rates are rising in many high-income countries, but remain low compared with those in low-income and middle-income settings. This Review aims to summarise the current epidemiology and knowledge on transmission and treatment of syphilis in pregnancy, and proposes measures to reduce the rising incidence seen worldwide. We also describe emerging diagnostic and treatment tools to prevent vertical transmission and improve management of congenital syphilis. Finally, we outline a programme of public health priorities, which include research, clinical, and preventive strategies. [ABSTRACT FROM AUTHOR]

Introduction: There is growing interest in health, developmental and survival outcomes of children who are born HIV‐free to women living with HIV (children born HIV‐free). To date, the research agenda has been largely determined by researchers, funders and policy makers, with limited involvement of parents, who are key stakeholders. Researchers at UCL Great Ormond Street Institute of Child Health in partnership with community‐based organisation 4M Network of Mentor Mothers conducted two workshops with parents in March 2022 to establish research priorities for children born HIV‐free, and key considerations for methodological approaches both to research and engagement with the affected communities. Discussion: When exploring research on children born HIV‐free, we consider the following: what aspects of current research are aligned with women and parents' priorities, what is missing and what approaches would be preferred. A holistic approach to research on children born HIV‐free should be prioritised, focussing on a breadth of outcomes and how they intersect. Secondary use of existing data sources should be maximised to facilitate this, with a view of monitoring the long‐term effects of fetal antiretroviral drug exposure alongside other key health and developmental outcomes. Involving and engaging with parents, and children where possible, must be at the heart of research design to maximise relevance and impact of findings for the affected communities. Potential barriers to engaging with individuals who were children born HIV‐free include parental disclosure and individuals not identifying as a child born HIV‐free to a mother living with HIV. Stigma‐free language must be incorporated into the vocabulary of researchers and other stakeholders, avoiding reference to exposure; we propose the term "children born HIV‐free." Conclusions: Mothers and parents living with HIV should be involved in research about their children born HIV‐free and are key in identifying research priorities so that findings may translate into an impact on their children's health and wellbeing. Meaningful involvement of women living with HIV through trusted community partners is an effective mechanism by which to elicit views on research about their children. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Ukraine Birth Cohort of Children With Vertically Acquired HIV Infection," by Saboura Mahdavi, Claire Thorne, Ruslan Malyuta, Igor Semenenko and Tatyana Pilipenko.

A letter to the editor is presented which discusses the increased risk of mother-to-child transmission among human immunodeficiency virus (HIV)-infected pregnant women with serological tests positive for syphilis.

Presents a letter to the editor in response to a letter on mother-to-child transmission of HIV published in the October 2005 issue of the journal "Clinical Infectious Diseases."

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/mm3 vs. 251-350 cells/mm3 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. [ABSTRACT FROM AUTHOR]

Objectives: Pregnancy and post-partum viral load suppression is critical to prevent mother-to-child HIV transmission and ensure maternal health. We measured viraemia risk before, during and after pregnancy in HIV-infected women.Methods: Between 2010 and 2015, 1425 HIV-infected pregnant women on lifelong antiretroviral therapy (ART) for at least six months pre-pregnancy were enrolled in a cohort study in rural KwaZulu-Natal, South Africa. Odds ratios were estimated in multilevel logistic regression, with pregnancy period time-varying.Results: Over half of 1425 women received tenofovir-based regimens (n = 791). Median pre-pregnancy ART duration was 2.1 years. Of 988 women (69.3%) with pre-pregnancy viral loads, 82.0%, 6.8% and 11.2% had VL <50, 50-999 and ≥1000 copies/ml, respectively. During pregnancy and at six, 12 and 24 months, viral load was ≥1000 copies/ml in 15.2%, 15.7%, 17.8% and 16.6% respectively; viral load <50 was 76.9%, 77%, 75.5% and 75.8%, respectively. Adjusting for age, clinical and pregnancy factors, viraemia risk (viral load ≥50 copies/ml) was not significantly associated with pregnancy [adjusted OR (aOR) 1.31; 95% CI 0.90-1.92], six months (aOR 1.30; 95% CI 0.83-2.04), 12 months (aOR 0.96; 95% CI 0.58-1.58) and 24 months (aOR 1.40; 95% CI 0.89-2.22) post-partum. Adjusting for ART duration-pregnancy period interaction, viraemia risk was 1.8 during pregnancy and twofold higher post-partum.Conclusions: While undetectable viral load before pregnancy through post-partum was common, the UNAIDS goal to suppress viraemia in 90% of women was not met. Women on preconception ART remain vulnerable to viraemia; additional support is required to prevent mother-to-child HIV transmission and maintain maternal health. [ABSTRACT FROM AUTHOR]

Background: Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started.Methods: Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression.Results: In adjusted analyses, ART-naïve (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS.Conclusions: In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman's health. [ABSTRACT FROM AUTHOR]

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

Introduction: The prevalence of gestational diabetes (GD) is increasing globally. While universal risk factors for GD are reasonably well understood, questions remain regarding risks for women living with HIV (WLWH). We aimed to describe GD prevalence, evaluate associated maternal risk factors and assess specific birth outcomes in WLWH in the UK and Ireland. Methods: We analysed all pregnancies (≥24 weeks' gestation) in women diagnosed with HIV before delivery, reported to the UK‐based Integrated Screening Outcomes Surveillance Service between 2010 and 2020. Every report of GD was considered as a case. A multivariable logistic regression model, adjusted for women with more than one pregnancy fitted with generalized estimating equations (GEE) assessed the effect of independent risk factors. Results: There were 10,553 pregnancies in 7916 women, of which 460 (4.72%) pregnancies had reported GD. Overall, the median maternal age was 33 years (Q1:29–Q3:37), and 73% of pregnancies were in Black African women. WLWH with GD (WLWH‐GD) were older (61% vs. 41% aged ≥35 years, p < 0.001) and more likely to be on treatment at conception (74% vs. 64%, p < 0.001) than women without GD. WLWH‐GD were more likely to have a stillbirth (odds ratio [OR]: 5.38, 95% CI: 2.14–13.5), preterm delivery (OR: 2.54, 95% CI: 1.95–3.32) and fetal macrosomia (OR: 1.14, 95% CI: 1.04–1.24). Independent risk factors for GD included estimated year of delivery (GEE‐adjusted odds ratio [GEE‐aOR]: 1.14, 95% CI: 1.10–1.18), advanced maternal age (≥35 years) (GEE‐aOR: 2.87, 95% CI: 1.54–5.34), Asian (GEE‐aOR: 2.63, 95% CI: 1.40–4.63) and Black African (GEE‐aOR: 1.55, 95% CI: 1.13–2.12) ethnicity. Timing and type of antiretroviral therapy showed no evidence of a relationship with GD in multivariable analyses; however, women with a CD4 count ≤350 cells/μl were 27% less likely to have GD than women with CD4 counts >350 cells/μl (GEE‐aOR: 0.73, 95% CI: 0.50–0.96). Conclusions: GD prevalence increased over time among WLWH but was not significantly different from the general population. Maternal age, ethnicity and CD4 count were risk factors based on available data. Stillbirth and preterm delivery were more common in WLWH‐GD than other WLWH over the study period. Further studies are required to build upon these results. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%–40% of vertically acquired HCV infections clear spontaneously within 4–5 years. Methods Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA–negative infants in whom RNA was not detectable until after 6 weeks. Results Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1–81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1–18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0–76.9), 39.7% (CrI, 17.9–65.9), and 20.9% (CrI, 4.6–44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. Conclusions Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment. [ABSTRACT FROM AUTHOR]

Background: The evidence on the effect of pregnancy on acquiring HIV is conflicting, with studies reporting both higher and lower HIV acquisition risk during pregnancy when prolonged antiretroviral therapy was accessible. The aim of this study was to assess the pregnancy effect on HIV acquisition where antiretroviral therapy was widely available in a high HIV prevalence setting.Methods: This is a retrospective cohort study nested within a population-based surveillance to determine HIV incidence in HIV-uninfected women from 15 to 49 years from 2010 through 2015 in rural KwaZulu-Natal. HIV incidence per 100 person-years according to pregnancy status (not pregnant, pregnant, to eight weeks postpartum) were measured in 5260 HIV-uninfected women. Hazard ratios (HR) were estimated by Cox proportional hazards regression with pregnancy included as a time varying variable.Results: Overall, pregnancy HIV incidence was 4.5 per 100 person-years (95% CI 3.4-5.8), higher than non-pregnancy (4.0; 95% CI 3.7-4.3) and postpartum incidences (4.2 per 100 person-years; 95% CI 2.3-7.6). However, adjusting for age, and demographic factors, pregnant women had a lower risk of acquiring HIV (HR 0.4; 95% CI 0.2-0.9, P = 0.032) than non-pregnant women; there were no differences between postpartum and non-pregnant women (HR 1.2; 95% CI 0.4-3.2; P = 0.744). In models adjusting for the interaction of age and gravidity, pregnant women under 25 years with two or more pregnancies had a 2.3 times greater risk of acquiring HIV than their older counterparts (95% CI 1.3-4.3; P = 0.008).Conclusions: Pregnancy had a protective effect on HIV acquisition. Elevated HIV incidence in younger women appeared to be driven by those with higher gravidity. The sexual and biological factors in younger women should be explored further in order to design appropriate HIV prevention interventions. [ABSTRACT FROM AUTHOR]

Evidence suggests children HIV‐exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV‐exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother‐to‐Child HIV Transmission Programme after Option B+ implementation (2014–2018). Anthropometry was measured at enrolment (age 1–6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight‐for‐age (WAZ) and length‐for‐age (LAZ) z‐scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi‐variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82–6.17]), which was modified by co‐trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi‐faceted health risks, alongside maternal ART prescription, and follow‐up of mother‐child pairs. Key messages: Understanding the health risks of children HIV‐exposed and uninfected (CHEU) and the impact on their growth is of paramount importance for optimizing their health.This is one of the first studies examining correlates of CHEU growth since the implementation of Option B+ and uses a random subsample of a nationally representative cohort of women with HIV and CHEU in Malawi.Factors associated with stunting included infant low birthweight, optimal feeding, co‐trimoxazole prophylaxis, and maternal employment.Interventions targeting modifiable risk factors, alongside maternal antiretroviral therapy, and improved nutritional follow‐up of CHEU will contribute to improving CHEU growth in Malawi. [ABSTRACT FROM AUTHOR]

Background: The UK National Screening Committee currently recommends against antenatal screening for Hepatitis C virus (HCV) infection in England due to lack of HCV prevalence data and treatment licensed for use in pregnancy. We aimed to produce regional and national estimates of the number and proportion of livebirths to HCV seropositive women in England in 2013 and 2018. Methods: A logistic regression model fitted in the Bayesian framework estimated probabilities of HCV seropositivity among 24,599 mothers delivering in the North Thames area of England in 2012 adjusted by maternal age and region of birth. These probabilities were applied to the underlying population structures of women delivering livebirths in England in 2013 and 2018 to estimate the number of livebirths to HCV seropositive women in these years nationally and by region. The Bayesian approach allowed the uncertainty associated with all estimates to be properly quantified. Results: Nationally, the estimated number of livebirths to women seropositive for HCV for England was 464 (95% credible interval [CI] 300–692) in 2013 and 481 (95%CI 310–716) in 2018, or 70.0 (95%CI 45.0–104.1) per 100,000 and 76.9 (95%CI 49.5–114.4) per 100,000 in these years respectively. Regions with the highest estimated number of livebirths to HCV seropositive women in 2013 and 2018 included London with 118.5 and 124.4 and the South East with 67.0 and 74.0 per 100,000 livebirths. Conclusion: Few previous studies have investigated HCV among pregnant women in England. These findings complement and supplement existing research by providing national and regional estimates for the number of livebirths to HCV seropositive women in England. Bayesian modelling allows future national and regional estimates to be produced and the associated uncertainty to be properly quantified. [ABSTRACT FROM AUTHOR]

Background In the absence of evidence-based guidelines, we investigate current European practices for the clinical management and treatment of children coinfected with HIV and Hepatitis C virus (HCV). Material and methods A semi-structured questionnaire survey in clinical centres from 7 European countries who were either enrolling in the European Collaborative Study of HIV-infected pregnant women and their children or the European Paediatric HCV Network of children born to HCV-infected mothers. Results To date we have received responses from clinicians from 16 centres, caring for a total of 35 HIV/HCV coinfected children. Four centres were not currently following any coinfected children. Only one centre had a written policy for the management and treatment of HIV/HCV coinfected children and in most other centres (8/11, 72%) decisions regarding the care of coinfected children were taken at the hospital or departmental level with only 3 out of 11 centres relying on regional or national decision-making. In addition to standard laboratory tests for monitoring HIV disease (HIV RNA quantification, CD4 counts etc), 6/12 centres also performed HCV RNA PCR tests at least annually and 6/12 centres carried out ALT and AST tests at least every 6 months in coinfected children. Liver biopsy was rarely performed but liver ultrasound was performed in 5 out of 12 centres at least annually. 91% of 11 centres performed HCV genotyping on all HIV/HCV coinfected children and 88% of 8 centres monitored for evidence of hepatotoxicity in coinfected children receiving antiretroviral treatment for HIV disease. Only one centre had ever treated coinfected children for HIV and HCV infections concurrently but 4/7 other centres stated they would consider treatment at the same time if necessary. In the situation of an HIV/HCV coinfection diagnosis later in childhood, 3/7 respondents stated that they would treat HCV infection before starting HIV therapy. Conclusions In the absence of guidelines for the clinical management of children coinfected with HIV and HCV, practices throughout Europe vary widely. Individual centres see relatively few coinfected children and therefore a lack of experience in the management of this group and the lack of evidence-based policy may be a barrier to achieving optimal care and treatment. This survey highlights the importance of research focused on this group of children to inform guidelines for their best possible care. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Antiretroviral Therapy During Pregnancy and the Risk of an Adverse Outcome" in the June 13, 2002 issue.

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes. [ABSTRACT FROM AUTHOR]

Introduction: As new antiretrovirals (ARVs), including long‐acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization. Discussion: This paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under‐reporting (e.g. in voluntary registries), few data sources from resource‐limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource‐limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real‐world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV. Conclusions: Looking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and quality of surveillance in pregnancy. The platform will be leveraged to ensure that appropriate contributions and strategic actions by relevant stakeholders are implemented. [ABSTRACT FROM AUTHOR]

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

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

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate acceptance, feasibility and difficulties in the application of a policy of vaginal delivery in selected cases in HIV-infected women.Study Design: HIV-infected women delivering March 2002 to December 2004 and enrolled in a prospective observational study in a University hospital tertiary care center were included. A vaginal delivery was not considered if labor before 36 weeks of pregnancy, preterm premature rupture of membranes, on non-highly active antiretroviral therapy (HAART) or viral load >1000copies/mL. Main outcome measures were mode of delivery, prematurity, acceptance of vaginal delivery and mother-to-child transmission of HIV infection.Results: The study included 91 pregnancies, with a total of 95 fetuses. Eighty percent (n=73) of women knew their HIV infection status before becoming pregnant and 57 (63%) were on HAART at conception. Median gestational age at delivery was 37 weeks (range 22-41). Twelve women delivered a live-born before 36 weeks, all with a caesarean section. Among 74 women who reached 36 weeks gestation, 47 (64%) met the pre-established criteria for vaginal delivery, of whom 21 (45%) delivered vaginally. The most common reason for not having a vaginal delivery was the woman's request for a caesarean section. No cases of HIV vertical transmission occurred (0/90, 95% CI 0-4.02%).Conclusion: Recommending vaginal delivery among HIV-infected women in selected cases was well accepted, particularly once the policy became established. Nevertheless, a high proportion of HIV-infected women will continue to require caesarean section delivery. [ABSTRACT FROM AUTHOR]