Maternal HIV Infection Research Articles

Increase in Cases of Perinatal HIV Transmission in Maryland in 2022.

The perinatal transmission of HIV is preventable through a regimen that includes testing of all pregnant individuals, antiretroviral treatment (ART) for the pregnant individual, prophylactic or preventative ART for the infant, and cesarean section delivery for mothers with HIV viremia at the time of delivery. Under this protocol, the United States has seen a significant decline in the perinatal transmission of HIV and achieved a perinatal HIV transmission rate of 0.9% in 2019. However, despite this progress nationally and after zero transmissions in 2021, Maryland recorded 6 cases of perinatal HIV diagnoses in 2022. Each of the 3 major referral centers for pediatric HIV patients in Maryland reported 2 new cases in 2022. A root cause analysis of the cases identified risk factors including delayed entry into perinatal and HIV care, premature birth, maternal adherence challenges in the setting of substance use and other adverse social determinants of health, and failure to diagnose maternal HIV infection in a timely way. All patients were successfully linked to care and initiated on ART. Multiple factors contributed to the 2022 increase in cases of perinatal HIV in Maryland. To achieve and then sustain the elimination of perinatal HIV transmission, the constancy of systems that eliminate barriers for all pregnant people to access testing, prevention, and treatment is critical.

Maternal HIV infection and various HIV antiretroviral regimens differentially affect placental System L-amino acid transporters

Maternal HIV infection and various HIV antiretroviral regimens differentially affect placental System L-amino acid transporters

Does Maternal HIV Infection Affect Neonatal Outcomes?

Pregnancy among women infected with HIV is classified as a high-risk pregnancy. While previous research has indicated an elevated likelihood of preterm birth, low birth weight, and early gestational age in infants born to mothers with HIV, the correlation between maternal HIV infection and different neonatal results remains unclear. This study aims to investigate the impact of maternal HIV infection on after-birth neonatal outcomes using machine learning (ML) and statistical methods. A case-control study is conducted through a three-stage process: Initially, the outcomes among newborns from HIV-positive mothers are identified through a combination of literature review and expert survey. Subsequently, data are paired at a 1:2 ratio based on gestational age with infants from HIV-positive mothers (n=48) compared to HIV-negative mothers (n=96) as the control group. Finally, various feature selection techniques are applied to identify outcomes that exhibit significant differences between the two groups. The statistical analysis showed that the rate of addiction among HIV-positive mothers is higher than that of the HIV-negative group. The need for mechanical ventilation and duration of ventilator-assisted breathing in infants born to HIV-positive mothers are significantly higher than in infants born to HIV-negative mothers. Moreover, based on feature selection methods, increasing the need for mechanical ventilation and reducing surfactant administration were two important outcomes. To investigate the impact of maternal HIV infection on neonatal outcomes, various statistical and machine learning-based feature selection techniques were implemented, and the results showed that the presented methods can be utilized to examine the potential impacts of different diseases contracted by the mother on the infant.

Effects of maternal HIV infection on low, very low, and extremely low birth weight: a population-based study in Brazil

Effects of maternal HIV infection on low, very low, and extremely low birth weight: a population-based study in Brazil

Preterm birth among women with HIV: impact of preconception cART initiation.

To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes. Prospective observational cohort. Urban government-run clinic at Chawama Hospital in Lusaka, Zambia. A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating. From August 2019 to November 2022, pregnant women were enrolled in a 1 : 1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis. PTB (<37 weeks) and SGA. There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection. HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.

Useful Clinical Criteria for Identifying Neonates with Congenital Cytomegalovirus Infection at Birth in the Context of an Expanded Targeted Screening Program.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). Targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, the inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference < 10th centile, failed hearing screen, and prematurity. During the first three years of use of this program (2021-2023), 940 (12.3%) of 7651 live-born infants were tested. The most common indication was birthweight < 10th centile (n = 633, 67.3%). Eleven neonates were diagnosed as congenitally infected, for a prevalence of 1.17% (95%CI 0.48-1.86) on tested neonates and of 0.14% (95%CI 0.06-0.23) on live-born infants. None of the cCMV-infected newborns had a failed hearing screen as a testing indication. Implementation of an expanded cCMV screening program appears feasible and of clinical value.

HIV-related immune activation attenuates polyfunctional IgG and memory B-cell responses to Tdap immunization during pregnancy

Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIHNIAID1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\mathrm{\\alpha }$$\\end{document}-KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Impact of maternal HIV infection on perinatal outcomes: A systematic review.

Maternal HIV infection remains a significant global health concern with potential repercussions on perinatal outcomes. Emphasis on early intervention to improve peri- and postnatal outcomes in infected mothers and infants is a valid therapeutic concern. To comprehensively analyze perinatal outcomes associated with maternal HIV infection and evaluate adverse effects associated with the HIV infection in the existing literature. A comprehensive search of PubMed, MEDLINE, and Google Scholar was conducted from 2013 to September 2023, using relevant MeSH terms. The included studies encompassed original studies, cross-sectional, prospective, retrospective studies and observational studies focused on perinatal outcomes in the context of maternal HIV infection. The selected studies underwent rigorous data collection and comprehensive quality checks and adhered to the PRISMA guidelines. Nine eligible studies from Brazil, China, India, Malawi, Nigeria, Tanzania, the USA, and Canada were included. These studies have consistently demonstrated that maternal HIV infection is associated with adverse perinatal outcomes. The analysis revealed a higher risk of preterm birth (OR 1.57, 95% CI: 1.39-1.78), low birth weight (OR 1.33, 95% CI: 1.18-1.49), and small for gestational age (OR 1.38, 95% CI: 1.24-1.53) among infants born to mothers living with HIV. Notably, the impact of antiretroviral treatment (ART) on these outcomes varied, but maternal HIV infection remained a significant risk factor regardless of income level and geographic region. Maternal HIV infection is consistently associated with adverse perinatal outcomes, emphasizing the need for targeted interventions and improved prenatal care in pregnant women with HIV infection.

Immunologic consequences of maternal HIV infection in the uninfected newborn

Immunologic consequences of maternal HIV infection in the uninfected newborn

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis

The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2=0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2=0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2=0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. None.

Eosinophilic Modulation of Neonatal Vaccine Immune Responses in HIV-Exposed Infants

The intricate interplay between eosinophils and neonatal vaccine immune responses in HIV-exposed infants has emerged as a captivating avenue of research, offering insights into the multifaceted dynamics of early-life immunity. This review synthesizes current knowledge on the eosinophilic modulation of immune responses following neonatal vaccination in the unique context of HIV exposure. We explore the potential roles of eosinophils in shaping adaptive immunity, influencing vaccine efficacy, and contributing to the delicate balance between tolerance and protective immunity during the critical early stages of life. Additionally, we discuss the implications of maternal HIV infection on eosinophil function and the subsequent impact on neonatal vaccine responses. Through a comprehensive analysis of existing literature, we aim to provide a foundation for future research directions and the development of tailored immunization strategies for this vulnerable population.

Prenatal ultrasound screening and pregnancy outcomes in HIV-positive women in Germany: results from a retrospective single-center study at the Charité-Universitätsmedizin Berlin.

The aim of this study was to investigate the rate of Mother-to-child-transmission (MTCT) in women living with HIV (WLWH) in a tertiary care institution. Furthermore, we aimed to assess prenatal ultrasound screening for fetal anomalies and outcomes in high-risk pregnancies due to maternal HIV infection." In this single-center study, retrospective data related to pregnancy and childbirth were collected from 420 WLWH. All data were evaluated descriptively. From January 2014 to December 2020, a total number of 420 pregnant WLWH delivered 428 newborns. 415 (98.8%) were receiving antiretroviral therapy (ART) and 88.8% had a viral load of < 50 cop/ml prior delivery. 46 (11%) of the newborns were born prematurely. Low birth weight < 2500g occurred in 38 (9.1%) of the children. 219 (52.1%) caesarean sections (CS) were performed. The most frequent indication for an elective CS was a previous CS (70.2%). 8 severe malformations were detected using first and second trimester ultrasound. In one child, MTCT was detected postpartum, resulting in an HIV transmission rate of 0.2% in the presented cohort. The low rate of vertical HIV-transmission in our cohort of 0.2% is the result of interdisciplinary prenatal care and high experience of healthcare providers in treatment of WLWH. Despite high ART coverage and adherence, good maternal immune system and very low vertical HIV transmission rate, maternal HIV infection remains a challenge in obstetric care. First and second ultrasound screening should be a part of prenatal care for HIV-infected women and should also be offered to HIV-negative women. A reduction of the rate of unnecessary elective caesarean deliveries in WLWH is necessary to reduce complications in subsequent pregnancies.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Prevalence of Tuberculosis in HIV- or Tuberculosis-exposed neonates at the University Teaching Hospital in Lusaka over a period of six months

Background: Tuberculosis (TB) is the leading cause of mortality globally and represents a major health problem. The burden of TB in Zambia is among the highest in the African region with a national prevalence estimated at 455/100 000 for all age groups. A large proportion of people with TB are in the reproductive age group as such may either be pregnant or have young children. As at 2014 the prevalence of TB among women attending antenatal care in Zambia was estimated to be 1.5% in HIV infected women and 1.4% in uninfected women. There is a close association between maternal TB and HIV infection and postpartum infant morbidity and mortality. TB in neonates is very rare but a tenfold increase in the risk of acquiring TB in infants born to HIV infected mothers has been documented. Methods: A cross sectional study was conducted to establish the prevalence of tuberculosis in neonates exposed to either HIV or TB, or to both TB and HIV. The study included neonates aged 28 days and below that were admitted to the intensive care unit (NICU) and nurseries on general pediatric wards at the University teaching hospital. Mothers to neonates that had a positive rapid HIV test were approached, made aware of the study and invited to participate by giving consent to have their baby included in the study. When consent was granted, basic demographic details and medical information were collected. One gastric lavage sample was collected before the first feed of the day and analysed using Xpert MTB- RIF test. Results: One hundred forty-nine consecutive neonates that met the inclusion criteria were enrolled in the study. The average age of the neonates was nine days, 49 % had mean birth weight of 2.50kg (0.85 SD), 86 full term delivery and 73 (49%) were male. One hundred, ten (110) were born to multiparous (74%) vs 38 primiparous (26%) mothers. All the neonates enrolled in the study were HIV exposed and only one neonate was exposed to both TB and HIV. Mycobacterium tuberculosis was detected in 2 out 149 samples analysed using the Xpert MTB-RIF test. None were positive for rifampicin resistance Conclusion: The prevalence of TB using Xpert MTB-RIF test performed on gastric aspirates of HIV exposed neonates admitted to the University teaching hospital is 1.3 %.

Metabolomic profiling of preterm birth in pregnant women living with HIV

BackgroundPreterm birth is a leading cause of death in children under the age of five. The risk of preterm birth is increased by maternal HIV infection as well as by certain antiretroviral regimens, leading to a disproportionate burden on low- and medium-income settings where HIV is most prevalent. Despite decades of research, the mechanisms underlying spontaneous preterm birth, particularly in resource limited areas with high HIV infection rates, are still poorly understood and accurate prediction and therapeutic intervention remain elusive.ObjectivesMetabolomics was utilized to identify profiles of preterm birth among pregnant women living with HIV on two different antiretroviral therapy (ART) regimens.MethodsThis pilot study comprised 100 mother-infant dyads prior to antiretroviral initiation, on zidovudine monotherapy or on protease inhibitor-based antiretroviral therapy. Pregnancies that resulted in preterm births were matched 1:1 with controls by gestational age at time of sample collection. Maternal plasma and blood spots at 23–35 weeks gestation and infant dried blood spots at birth, were assayed using an untargeted metabolomics method. Linear regression and random forests classification models were used to identify shared and treatment-specific markers of preterm birth.ResultsClassification models for preterm birth achieved accuracies of 95.5%, 95.7%, and 80.7% in the untreated, zidovudine monotherapy, and protease inhibitor-based treatment groups, respectively. Urate, methionine sulfone, cortisone, and 17α-hydroxypregnanolone glucuronide were identified as shared markers of preterm birth. Other compounds including hippurate and N-acetyl-1-methylhistidine were found to be significantly altered in a treatment-specific context.ConclusionThis study identified previously known as well as novel metabolomic features of preterm birth in pregnant women living with HIV. Validation of these models in a larger, independent cohort is necessary to ascertain whether they can be utilized to predict preterm birth during a stage of gestation that allows for therapeutic intervention or more effective resource allocation.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (β = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (β = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Safety surveillance for PrEP in pregnant and breastfeeding women.

The risk of HIV acquisition is higher during pregnancy and postpartum than other times. Newly acquired maternal HIV infection associated with high primary viraemia, substantially increases the risk of vertical HIV transmission. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition. Currently available products include oral tenofovir/emtricitabine (TDF/FTC) and tenofovir alafenamide (TAF)/FTC), long-acting cabotegravir (CAB-LA) and the dapivirine ring (DVR). All except oral TDF/FTC have limited safety data available for use in pregnant and breastfeeding women. The safety of new PrEP agents for pregnant women and the fetus, infant and child, either exposed in utero or during breastfeeding is an ongoing concern for health care workers and pregnant and breastfeeding women, particularly as the safety risk appetite for antiretroviral (ARV) agents used as PrEP is lower in pregnant and breastfeeding women who are HIV-uninfected, compared to women living with HIV taking ARVs as treatment. With the widespread rollout of TDF/FTC among pregnant women in South Africa and other low-middle income countries (LMIC) and the potential introduction of new PrEP agents for pregnant women, there is a need for safety surveillance systems to identify potential signals of risk to either the mother or fetus, measure the burden of such a risk, and where appropriate, provide specific reassurance to PrEP users. Safety data needs to be collected across the continuum of the product life cycle from pre-licensure into the post-marketing period, building a safety profile through both passive and active surveillance systems, recognising the strengths and limitations of each, and the potential for bias and confounding. Pharmacovigilance systems that aim to assess the risk of adverse birth outcomes in pregnant women exposed to PrEP and other agents need to consider the special requirements of pregnancy epidemiology to ensure that the data derived from surveillance are sufficiently robust to inform treatment policies. Here we review the known safety profiles of currently available PrEP candidates in women of child-bearing potential, pregnancy and breastfeeding and discuss pragmatic approaches for such surveillance in HIV-endemic LMICs.

Association between maternal HIV infection and the risks of preterm birth and low birth weight in Chengdu, China: a propensity score matching approach

ObjectivesTo estimate the effect of HIV infection on the risk of preterm birth (PTB) and low birth weight (LBW) among Chinese pregnancy women.DesignA retrospective cohort study included HIV-positive pregnant women...

Time trends in perinatal outcomes among HIV-positive pregnant women in Northern Tanzania: A registry-based study.

Maternal HIV infection is associated with increased risk of having a preterm delivery, low birth weight baby, small for gestational age baby and stillbirth. Maternal use of combination antiretroviral treatment is also associated with preterm delivery and low birth weight, although the effects vary by the type of drugs and timing of initiation. To examine time trends in adverse perinatal outcomes among HIV-positive compared with HIV-negative women. Registry-based cohort study. Northern Tanzania, 2000-2018. Mother-baby pairs of singleton deliveries (n = 41 156). Perinatal outcomes of HIV-positive women were compared with HIV-negative women during time periods representing shifts in prevention of mother-to-child transmission guidelines. Monotherapy was used as first-line therapy before 2007 while combination antiretroviral treatment was routinely used from 2007. Log binomial and quantile regression were used to analyze the data. Preterm delivery, low birth weight, perinatal death, stillbirth, low Apgar score, transfer to neonatal care unit and small for gestational age. Overall, maternal HIV infection was associated with a higher risk of low birth weight and small for gestational age. Moreover, this pattern became more pronounced over time for low birth weight, the last time period being an exception. For other outcomes we found none or only a small overall association with maternal HIV infection, although a trend towards higher risk over time in HIV-positive compared with HIV-negative women was observed for preterm delivery and perinatal death. Quantile regression showed an increase in birth weight in babies born to HIV-negative women over time and a corresponding decline in birth weight in babies born to HIV-positive women. Unfavourable trends in some of the selected perinatal outcomes were seen for HIV-positive compared with HIV-negative women. Potential side-effects of combination antiretroviral treatment in pregnancy should be further explored.