Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study.

OBJECTIVE: To compare the vaginal microbiota of women living with HIV (WLWH) with the vaginal microbiota of women with recurrent bacterial vaginosis (BV) and healthy women without HIV to determine if there are differences in the vaginal microbiome, what factors influence these differences, and to characterise HIV clinical parameters including viral load and CD4 count in relation to the vaginal microbiome. DESIGN: Observational cohort study. SETTING: Canada. POPULATION: Women aged 18-49 years who were premenopausal and not pregnant were recruited into three cohorts: healthy women, WLWH and women with recurrent BV. METHODS: Demographic and clinical data were collected via interviews and medical chart reviews. Vaginal swabs were collected for Gram-stain assessment and microbiome profiling using the cpn60 barcode sequence. MAIN OUTCOME MEASURES: To compare overall community composition differences, we used compositional data analysis methods, hierarchical clustering and Kruskal-Wallis tests where appropriate. RESULTS: Clinical markers such as odour and abnormal discharge, but not irritation, were associated with higher microbial diversity. WLWH with unsuppressed HIV viral loads were more likely than other groups to have non-Gardnerella-dominated microbiomes. HIV was associated with higher vaginal microbial diversity and this was related to HIV viral load, with unsuppressed women demonstrating significantly higher relative abundance of Megasphaera genomosp. 1, Atopobium vaginae and Clostridiales sp. (all P < 0.05) compared with all other groups. CONCLUSIONS: In WLWH, unsuppressed HIV viral loads were associated with a distinct dysbiotic profile consisting of very low levels of Lactobacillus and high levels of anaerobes. TWEETABLE ABSTRACT: Vaginal microbiomes in WLWH with viral load >50 copies/ml have distinct dysbiotic profiles with high levels of anaerobes.

Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study.

OBJECTIVE: Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. DESIGN: The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. SETTING: Paediatric HIV clinics. POPULATION: Live-born infants born in Canada to WLWH between 2007 and 2017. METHODS: Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. MAIN OUTCOME MEASURES: Congenital anomalies. RESULTS: Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). CONCLUSION: Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. TWEETABLE ABSTRACT: Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.

Cancer incidence among HIV-positive women in British Columbia, Canada: Heightened risk of virus-related malignancies.

OBJECTIVES: We used population-based data to identify incident cancer cases and correlates of cancer among women living with HIV/AIDS in British Columbia (BC), Canada between 1994 and 2008. METHODS: Data were obtained from a retrospective population-based cohort created from linkage of two province-wide databases: (1) the database of the BC Cancer Agency, a province-wide population-based cancer registry, and (2) a database managed by the BC Centre for Excellence in HIV/AIDS, which contains data on all persons treated with antiretroviral therapy in BC. This analysis included women (≥ 19 years old) living with HIV in BC, Canada. Incident cancer diagnoses that occurred after highly active antiretroviral therapy (HAART) initiation were included. We obtained a general population comparison of cancer incidence among women from the BC Cancer Agency. Bivariate analysis (Pearson χ(2) , Fisher's exact or Wilcoxon rank-sum test) compared women with and without incident cancer across relevant clinical and sociodemographic variables. Standardized incidence ratios (SIRs) were calculated for selected cancers compared with the general population sample. RESULTS: We identified 2211 women with 12 529 person-years (PY) of follow-up who were at risk of developing cancer after HAART initiation. A total of 77 incident cancers (615/100 000 PY) were identified between 1994 and 2008. HIV-positive women with cancer, in comparison to the general population sample, were more likely to be diagnosed with invasive cervical cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma and Kaposi's sarcoma and less likely to be diagnosed with cancers of the digestive system. CONCLUSIONS: This study observed elevated rates of cancer among HIV-positive women compared to a general population sample. HIV-positive women may have an increased risk for cancers of viral-related pathogenesis.

A case series of third-trimester raltegravir initiation: Impact on maternal HIV-1 viral load and obstetrical outcomes.

OBJECTIVE: To describe the impact of initiating raltegravir (RAL)-containing combination antiretroviral therapy (cART) regimens on HIV viral load (VL) in pregnant women who have high or suboptimal VL suppression late in pregnancy. METHODS: HIV-infected pregnant women who started RAL-containing cART after 28 weeks' gestation from 2007 to 2013 were identified in two university hospital centres. RESULTS AND DISCUSSION: Eleven HIV-infected women started RAL at a median gestational age of 35.7 weeks (range 31.1 to 38.0 weeks). Indications for RAL initiation were late presentation in pregnancy (n=4) and suboptimal VL suppression secondary to poor adherence or viral resistance (n=7). Mean VL at the time of RAL initiation was 73,959 copies/mL (range <40 to 523,975 copies/mL). Patients received RAL for a median of 20 days (range one to 71 days). The mean decline in VL from the time of RAL initiation to delivery was 1.93 log, excluding one patient who received only one RAL dose and one patient with undetectable VL at the time of RAL initiation. After eight days on RAL, 50% of the women achieved a VL <1000 copies/mL (the threshold for recommended Caesarean section to reduce the risk for perinatal transmission). There were no cases of perinatal HIV transmission. CONCLUSION: The present study provides preliminary data to support the use of RAL-containing cART to expedite HIV-1 VL reduction in women who have a high VL or suboptimal VL suppression late in pregnancy, and to decrease the risk of HIV perinatal transmission while avoiding Caesarean section. Further assessment of RAL safety during pregnancy is warranted.

OBJECTIF: Décrire les répercussions de l'amorce d'une antirétrovirothérapie prophylactique associative (ARPA) contenant du raltégravir (RAL) sur la charge virale (CV) du VIH chez les femmes enceintes dont la suppression de la CV est élevée ou sous-optimale en fin de grossesse. MÉTHODOLOGIE: Les chercheurs ont extrait le dossier des femmes enceintes infectées par le VIH qui avaient amorcé une ARAP contenant du RAL après 28 semaines de grossesse dans deux centres hospitaliers universitaires entre 2007 et 2013. RÉSULTATS ET EXPOSÉ: Onze femmes infectées ont entrepris un traitement de RAL à une médiane de 35,7 semaines de grossesse (plage de 31,1 à 38,0 semaines). Les indications pour entreprendre le RAL étaient une présentation tardive au suivi de grossesse (n=4) et une suppression sous-optimale de la CV en raison d'un mauvais respect du traitement ou d'une résistance virale (n=7). La CV moyenne au début du traitement au RAL était de 73 959 copies/mL (plage de moins de 40 copies/mL à 523 975 copies/mL). Les patientes ont pris du RAL pendant une médiane de 20 jours (plage de un à 71 jours). La diminution moyenne de la CV entre le début du RAL et l'accouchement était de 1,93 log, à l'exception d'une patiente qui n'a reçu qu'une dose de RAL et d'une patiente dont la CV n'était pas décelable au moment d'entreprendre le RAL. Au bout de huit jours de RAL, 50 % des femmes présentaient une CV inférieure à 1 000 copies/mL (le seuil pour recommander une césarienne afin de réduire le risque de transmission périnatale). Il n'y a d'ailleurs eu aucun cas de transmission périnatale du VIH. CONCLUSION: La présente étude fournit des données provisoires pour soutenir l'utilisation d'ARPA contenant du RAL afin d'accélérer la réduction de la CV du VIH-1 chez les femmes qui présentaient une CV élevée ou une suppression sous-optimale de leur CV pendant la grossesse, ainsi que pour réduire le risque de transmission périnatale du VIH tout en évitant une césarienne. Une évaluation plus approfondie de l'innocuité du RAL est justifiée pendant la grossesse.

Maternal-infant transfer of SARS-CoV-2 antibodies following vaccination in pregnancy: A prospective cohort study.

OBJECTIVES: To measure and evaluate the impact of receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in pregnancy on immunoglobulin G (IgG) and immunoglobulin A (IgA) titres in maternal and infant samples. DESIGN: Prospective cohort study. SETTING: Tertiary obstetric centre. POPULATION OR SAMPLE: 52 pregnant women who received one or more SARS-CoV-2 vaccine doses during pregnancy and their neonates. METHODS: IgG and IgA concentrations against SARS-CoV-2 antigens were measured from samples collected at delivery and 4-6 weeks postpartum and compared using Spearman correlations. MAIN OUTCOME MEASURES: Maternal and infant IgG and IgA titres in response to vaccination and infection in pregnancy. RESULTS: In maternal serum collected at delivery, participants without evidence of prior infection who received 3 + doses of a SARS-CoV-2 vaccine had higher Anti-Spike (S) IgG geometric mean concentrations (log10 AU/mL)(GMC) than those who received 2 doses (3 + Doses = 5.00, 2 Doses = 4.60, p = 0.08). The differences in IgG Anti-S GMC were statistically significant in cord serum, and in postpartum samples of maternal serum, infant serum and breast milk (Cord GMCs: 3 + Doses = 5.32, 2 Doses = 4.98, p < 0.05; Postpartum maternal serum GMCs: 3 + Doses = 5.25, 2 Doses = 4.57, p < 0.001; Postpartum infant serum GMCs: 3 + Doses = 5.10, 2 Doses = 4.72, p = 0.03; Postpartum breast milk GMCs: 3 + Doses = 2.61, 2 Doses = 1.94, p < 0.0001). Among participants with 3 + Doses, those with evidence of SARS-CoV-2 infection had statistically significant higher anti-S IgG GMCs than those without prior infection (Maternal serum at delivery: SARS-CoV-2+=5.65, SARS-CoV-2-=5.00, p = 0.004; Cord: SARS-CoV-2+=5.68, SARS-CoV-2-=5.32, p = 0.02; Postpartum maternal serum: SARS-CoV-2+=5.66, SARS-CoV-2-=5.25, p < 0.001; postpartum infant serum: SARS-CoV-2+=5.50, SARS-CoV-2-=5.10, p = 0.003; Postpartum breast milk: SARS-COV-2+=3.25, SARS-COV-2-=2.61, p = 0.009). Significant positive correlations were found for anti-S IgG titres between paired maternal and infant samples at delivery and postpartum (Delivery: R = 0.91, p < 0.001; postpartum: R = 0.86, p < 0.001). CONCLUSIONS: Receipt of a SARS-CoV-2 vaccine and SARS-CoV-2 infection elicit strong IgG and IgA antibody responses in pregnant women with evidence of transplacental transfer to the fetus.

Reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy in Canada: A national prospective cohort study.

OBJECTIVE: To describe self-reported reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy. DESIGN: National, prospective cohort study. SETTING: Participants across Canada were enrolled from July 2021 until June 2022. POPULATION: Individuals pregnant during the COVID-19 pandemic, regardless of vaccination status, were included. METHODS: The Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals (COVERED) was advertised through traditional and social media. Surveys were administered at baseline, following each vaccine dose if vaccinated, pregnancy conclusion, and every two months for 14 months. Changes to pregnancy or vaccination status, SARS-CoV-2 infections, or significant health events were recorded. MAIN OUTCOME MEASURES: Reactogenicity (local and systemic adverse events, and serious adverse events) within 1 week post-vaccination, pregnancy and neonatal outcomes, and subsequent SARS-CoV-2 infection. RESULTS: Among 2868 participants who received 1-2 doses of a COVID-19 vaccine during pregnancy, adverse events described included: headache (19.5-33.9%), nausea (4.8-13.8%), fever (2.7-10.2%), and myalgia (33.4-42.2%). Reactogenicity was highest after the 2nd dose of vaccine in pregnancy. Compared to 1660 unvaccinated participants, there were no statistically significant differences in adverse pregnancy or infant outcomes, aside from an increased risk of NICU admission ≥ 24 h among the unvaccinated group. During follow-up, there was a higher rate of participant-reported SARS-CoV-2 infection in the unvaccinated compared to the vaccinated group (18[47.4%] vs. 786[27.3%]). CONCLUSIONS: Participant-reported reactogenicity was similar to reports from non-pregnant adults. There was no increase in adverse pregnancy and birth outcomes among vaccinated vs. unvaccinated participants and lower rates of SARS-CoV-2 infection were reported in vaccinated participants. TWEETABLE ABSTRACT: No significant increase in adverse pregnancy or infant outcomes among vaccinated versus unvaccinated pregnant women in Canada.

Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination.

OBJECTIVES: Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks. Cerebral lamination patterns of normal fetal brain development have been described histologically, by postmortem in-vitro magnetic resonance imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate the sonographic appearance of laminar organization of the cerebral wall in normal and abnormal brain development. METHODS: This was a retrospective study of ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral lamination patterns for gestational age, at 17-38 weeks' gestation. We investigated the visibility of the subplate zone relative to the intermediate zone and correlated characteristic sonographic findings of cerebral lamination with gestational age in order to evaluate transient structures. RESULTS: In the normal cohort, the subplate zone-intermediate zone interface was identified as early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these fetuses, the subplate zone appeared anechoic and the intermediate zone appeared homogeneously more echogenic than did the subplate zone. In the 22 fetuses between 28 and 34 weeks, there was a transition period when lamination disappeared in a variable fashion. The subplate zone-intermediate zone interface was not identified in any fetus after 34 weeks (n=13). There were three patterns of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks (n=32), in association with severe ventriculomegaly, diffuse ischemia, microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly, stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or encephalocele; (3) increased prominence and echogenicity of the intermediate zone before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks (n=10), associated with Type 1 lissencephaly or CMV infection. There was a mixed focal/diffuse pattern in two fetuses. In CMV infection, the earliest indication of the infection was focal heterogeneity and increased echogenicity of the intermediate zone, which predated the development of microcephaly, ventriculomegaly and intracranial calcification. CONCLUSIONS: The fetal subplate and intermediate zones can be demonstrated reliably on routine sonography before 28 weeks and disappear after 34 weeks. These findings represent normal gestational age-dependent transient laminar patterns of cerebral development and are consistent with histological studies. Abnormal fetal cerebral lamination patterns for gestational age are also visible on sonography, and may indicate abnormal brain development.

Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia.

OBJECTIVE: Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls. DESIGN AND METHOD: A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays. SETTING: A single tertiary maternity hospital in Vancouver, Canada. POPULATION: Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (>or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls. RESULTS: Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups. CONCLUSIONS: These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

Intention of parents to have male children vaccinated with the human papillomavirus vaccine.

BACKGROUND: Although already approved for use in males in some jurisdictions, there is little information about parental attitudes toward having their sons receive the human papillomavirus (HPV) vaccine. The goal of this study was to ascertain parental intentions to vaccinate their sons with an HPV vaccine and to determine factors that predict this intention. METHODS: Parents of children aged 8-18 years were recruited from across Canada through random digit dialling. Participants were asked to respond to a series of questions in the context of a Grade 6 (age 11/12 years old), publicly funded school-based HPV vaccine programme, including their intention to vaccinate their sons with the HPV vaccine. Parents were also asked about a series of characteristics thought to predict intention to vaccinate as well as demographic characteristics. Backwards logistic regression was conducted to calculate adjusted odds ratios (AOR) to identify the factors that are predictive of parents' intention to vaccinate their son(s) against HPV. RESULTS: Of the 1381 respondents with male children, 67.8% (95% CI 65.3 to 70.3) intend to vaccinate their son(s) against HPV. Parents who had positive attitudes toward vaccines and the HPV vaccine in particular (AOR 41.5, 95% CI 9.5 to 181.7), parents who were influenced by subjective norms (AOR 7.8, 95% CI 5.8 to 10.5), parents who felt that the vaccine had limited influence on sexual behaviour (AOR 2.3, 95% CI 1.6 to 3.3) and parents who were aware of HPV (AOR 1.4, 95% CI 1.1 to 2.0) were significantly more likely to report an intention to vaccinate boys against HPV. In contrast, residence in British Columbia compared to Atlantic Canada (AOR 0.4, 95% CI 0.2 to 0.8) and higher education (AOR 0.7, 95% CI 0.5 to 0.9) were negatively associated with intention to vaccinate. Parents who reported an intention to vaccinate their daughters were also highly likely to report an intention to vaccinate their sons (kappa = 0.9, p<0.001). DISCUSSION: The majority of Canadian parents would intend to have their male children receive the HPV vaccine in the context of a publicly funded school-based immunisation programme. Overall attitudes toward vaccine, recommendations from health professionals and impact of the vaccine on sexual practices are important predictors of intention to have a male child receive the HPV vaccine.

Serious toxicity associated with continuous nevirapine-based HAART in pregnancy.

OBJECTIVE: This study was designed to determine the safety of nevirapine (NVP)-based highly active antiretroviral therapy (HAART) in a cohort of HIV-positive pregnant women. DESIGN: This was a prospective cohort study of HIV-positive pregnant women. POPULATION AND SETTING: All HIV-positive women treated with HAART during pregnancy from January 1997 to February 2004 at the British Columbia (BC) Women's Hospital in Vancouver, BC, Canada. METHODS: Demographic and clinical data were collected to compare antiretroviral drug toxicities in women treated antenatally with NVP-based or non-NVP-based HAART. Multivariate analyses were then used to investigate determinants of toxicity. RESULTS: From 1997 to 2004, 103 HIV-positive pregnant women received HAART. Equivalent numbers of women were initially treated with NVP-based (54%) and non-NVP-based (46%) HAART. The groups did not differ by clinical or demographic parameters and duration of HAART exposure was similar between groups. Toxicities necessitating treatment discontinuation were observed in 6 of 56 NVP-exposed women (2 cases each of grade 2, 3, and 4 toxicity) compared with 1 of 47 in the non-NVP-exposed women. First time use of NVP approached significance as a predictor for toxicity, with a toxicity rate of 12.5% (6/48) observed among those taking NVP for the first time (adjusted OR 2.68, 95% CI 0.49-14.6). CONCLUSION: Continuous NVP use in pregnancy resulted in a relatively higher rate of toxicity, and all cases of NVP toxicity occurred in women exposed to NVP for the first time during pregnancy.

Sudden infant death syndrome: the vitamin E/selenium iron hypothesis (dietary anti/pro-oxidant imbalance).

Cot death or Sudden Infant Death Syndrome (SIDS) remains a largely unexplained and unpreventable factor in infant mortality. The existence of a dietary link between SIDS and vitamin E/selenium deficiency, documented through veterinary evidence, is posited as an etiological factor. Further substantiation of this hypothesis is derived from infant nutrition practices and cases of SIDS in New Zealand.

A multi-channel hearing prosthesis for profound-to-total hearing loss.

A multi-channel cochlear implant hearing prosthesis providing 22 separate channels of stimulation has been developed. The electronics for the implantable receiver-stimulator have been incorporated on a single chip, using digital circuits and employing CMOS technology. The chip is enclosed in a titanium capsule with platinum/ceramic electrode feed-throughs. A pocket-sized speech processor and directional microphone extract the following speech parameters: signal amplitude, fundamental frequency and formant frequency. The fundamental frequency is coded as electric pulse rate, and formant frequency by electrode position. The speech processor has been realized using hybrid circuits and CMOS gate arrays. The multi-channel prosthesis has undergone a clinical trial on four postlingually deaf patients with profound-total hearing losses. The speech perception results indicate that they were able to obtain open-set speech recognition scores for phonetically balanced words, CID sentences and spondees. In all cases the tests showed significant improvements when using the cochlear prosthesis combined with lipreading compared to lipreading alone.