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BACKGROUND Compared to children who are HIV-unexposed and uninfected (CHUU), children who are HIV-exposed and uninfected (CHEU) experience more clinical complications. We investigated hospitalizations among CHEU by antenatal antiretroviral therapy (ART) exposure, in British Columbia, Canada. METHODS This retrospective controlled cohort study used administrative health data from 1990 to 2012. CHEU and CHUU were matched 1:3 for age, sex and maternal geographical area of residence. We determined adjusted odds ratios (aORs) via conditional logistic regression, adjusting for maternal risk factors. RESULTS A total of 446 CHEU and 1333 CHUU were included. Compared with CHUU, more CHEU experienced one or more lifetime hospitalization (47.3% vs. 29.8%), one or more neonatal hospitalization (40.4% vs. 27.6%), and any intensive care unit admission (28.5% vs. 9.2%). In adjusted analyses, CHEU experienced higher odds of any lifetime hospitalization (aOR 2.30, 95% confidence interval 1.81-2.91) and neonatal hospitalization (aOR 2.14, 95% confidence interval 1.68-2.73), compared with CHUU. There was, however, no difference in infection-related hospitalizations (9.0% vs. 7.5%), which were primarily respiratory tract infections among both CHEU and CHUU. CHEU whose mothers-initiated ART preconception showed lower odds of infection-related hospitalizations than children whose mothers initiated ART during pregnancy or received no ART. CONCLUSIONS CHEU experienced increased odds of hospitalization relative to CHUU. A substantial number of CHEU hospitalizations occurred within the neonatal period and were ICU admissions. Initiating ART preconception may reduce the risk of infection-related hospitalizations. These findings reinforce the benefit of ART in pregnancy and the need for ongoing pediatric care to reduce hospitalizations.

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.

In both high-and low-income countries, HIV-negative children born to HIV-positive mothers (HIVexposed, uninfected [HEU]) are more susceptible to severe infection than HIV-unexposed, uninfected (HUU) children, with altered innate immunity hypothesized to be a cause. Both the gut microbiome and systemic innate immunity differ across biogeographically distinct settings, and the two are known to influence each other. And although the gut microbiome is influenced by HIV infection and may contribute to altered immunity, the biogeography of immune-microbiome correlations among HEU children have not been investigated. To address this, we compared the innate response and the stool microbiome of 2-y-old HEU and HUU children from Belgium, Canada, and South Africa to test the hypothesis that region-specific immune alterations directly correlate to differences in their stool microbiomes.We did not detect a universal immune or microbiome signature underlying differences between HEU versus HUU that was applicable to all children. But as hypothesized, population-specific differences in stool microbiomes were readily detected and included reduced abundances of short-chain fatty acid producing bacteria in Canadian HEU children. Furthermore, we did not identify innate immune-microbiome associations that distinguished HEU from HUU children in any population. These findings suggest that maternal HIV infection is independently associated with differences in both innate immunity and the stool microbiome in a biogeographical population-specific way., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.ConclusionThe persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

Transitioning from pediatric to adult care is a complicated process for youth with chronic illnesses. This study elucidates the unique factors affecting transition preparedness and perception of adult HIV care among a cohort of young women with HIV. Between 2013 and 2015, 48 women with HIV, who had experience with pediatric HIV care, were enrolled in a large Canadian cohort study. Variables were self-reported during peer-administered surveys. Only 60% reported feeling prepared for transition. Having never had contact with child protection services ( P = .049), never been in foster care ( P = .011), never been in a group home ( P = .036), reporting a higher current CD4 count ( P = .033), and reporting a younger ideal age for transition ( P = .041) were associated with transition preparedness. Eighty-four percent reported equivalent or better HIV care following transition. Correlates of equivalent/better care following transition included lower personal income ( P = .023), higher CD4 count ( P = .021), care by an adult infectious diseases specialist ( P = .002), and transition preparedness ( P = .005). Our findings highlight the importance of adequate transition preparation and its effect on perception of care following transition.

OBJECTIVE To investigate factors contributing to preterm birth (PTB), including cART use and clinical and social determinants of health, in women living with HIV (WLWH) from British Columbia, Canada. DESIGN Retrospective observational cohort. METHODS We investigated the effect of cART use and other clinical and demographic factors on spontaneous PTB (sPTB) rates (

BACKGROUND: Vertical HIV transmission has declined in Canada, but missed opportunities for prevention continue to occur. We sought to determine the adequacy, and changes over time in adequacy, of uptake of maternal and neonatal antiretroviral therapy for the prevention of vertical HIV transmission, and to determine the vertical transmission rate over time and according to adequacy of antenatal antiretroviral therapy during the combination antiretroviral therapy era in Canada. METHODS: The Canadian Perinatal HIV Surveillance Program collects data annually through retrospective chart review concerning HIV-infected women and their infants. We determined receipt of adequate antiretroviral treatment (antenatal combination antiretroviral treatment for ≥ 4 wk, intrapartum intravenous zidovudine treatment and 4-6 wk of infant oral zidovudine treatment) and predictors of inadequate antenatal combination antiretroviral therapy (none or < 4 wk) in Canada in 1997-2016. RESULTS: We identified 3785 mother-infant pairs. Uptake of 4 weeks or more of antenatal combination antiretroviral therapy increased over time across all provinces/territories and regardless of maternal race/ethnicity or risk category (p < 0.001). During 2011-2016, 92 women (6.5%) received no or less than 4 weeks of antenatal combination antiretroviral therapy, 146 women (10.7%) received no intrapartum zidovudine treatment, and 43 infants (3.1%) received less than 4 weeks of zidovudine treatment. In multivariate analysis restricted to 2011-2016, higher uptake of adequate antenatal combination antiretroviral therapy was seen among black women than among Indigenous (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.23-7.26) or white (OR 1.87, 95% CI 0.99-1.27) women and in British Columbia/Yukon Territory than in Alberta (OR 3.31, 95% CI 1.06-10.32), Ontario (OR 3.16, 95% CI 1.08-9.26) or Quebec (OR 3.44, 95% CI 1.09-10.84). Among the 14 vertical HIV transmission events during 2011-2016 (vertical transmission rate 1.0%), maternal HIV infection was diagnosed before the onset of labour in 5 cases, and only 2 women received adequate antenatal combination antiretroviral therapy. INTERPRETATION: Efforts to improve timely access to care, HIV screening and treatment for all women, combined with enhanced resources targeting populations at increased risk for HIV infection, will be needed if vertical HIV transmission is to be eliminated in Canada.

Objectives: To compare muscle power between youth who acquired HIV perinatally and HIV unexposed uninfected (HUU) youth. Methods: We assessed muscle power (relative to body mass, Pmax/mass), muscle force normalized to body weight (Fmax/BW), force efficiency, jump height (Hmax) and velocity (Vmax) during a single two-legged jump with hands on waist on a force platform (Leonardo) in HIV+ youth (n=35, 9-21 y). Thirty-three and 22 participants returned at 12- and 24-months, respectively. We compared age- and sex-specific z-scores in the HIV+ youth to those in HUU controls (n=716, 9-21 y) adjusting for height and muscle cross-sectional area (MCSA, by pQCT). Results: At baseline, z-scores for Pmax/mass, Fmax/BW and Vmax were less than 1 standard deviation lower than HUU after adjusting for height and MCSA (p

We evaluated quadrivalent human papillomavirus vaccine seroresponses among 35 girls living with HIV (9-13 years of ages) and compared with data on girls without HIV, as part of a subgroup analysis. The quadrivalent human papillomavirus vaccine was safe and well tolerated. However, antibody response was significantly lower in girls living with HIV relative to girls without HIV. HIV virologic suppression predicted better antibody response.

Long-term outcomes of perinatal exposure to maternal antiretroviral therapy in HIV-exposed uninfected (HEU) children are unknown. However, both HIV antiretroviral therapy and autism spectrum disorder (ASD) have been associated with mitochondrial alterations. Leukocyte mitochondrial DNA (mtDNA) content can serve as a marker for mitochondrial dysfunction. In this cross-sectional, nested case-control study, HEU children with ASD were matched approximately 1:3 on age, sex, and ethnicity to HEU children without ASD, HIV-unexposed uninfected (HUU) controls, and HUU children with ASD. Leukocyte mtDNA content was measured using quantitative PCR. Among 299 HEU in this study, 14 (4.7%) were diagnosed with ASD, which is higher than the general population prevalence estimates. HEU children without ASD and HUU children with ASD had higher mtDNA content than HUU controls. HEU children with ASD had significantly higher mtDNA content than all other study groups. Our results suggest a clear association between elevated leukocyte mtDNA content and both HEU and ASD status. This may implicate mitochondrial dysfunction as a contributor to the high ASD prevalence observed in our cohort.

OBJECTIVES To assess and compare neurodevelopmental disorders in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children in British Columbia, Canada. To determine associations between these outcomes and in-utero exposure to antiretroviral drugs. DESIGN Retrospective controlled cohort study. METHODS Data were collected on 446 HEU children and 1323 HUU children (matched ∼1 : 3 for age, sex, and geocode) born between 1990 and 2012. Multivariable logistic regressions determined odds ratios of neurodevelopmental disorder diagnoses. RESULTS HEUs had three times higher odds of being born preterm (P

BACKGROUND Improving adherence to combined antiretroviral therapy (cART) can be challenging, especially among vulnerable populations living with HIV. Even where cART is available free of charge, social determinants of health act as barriers to optimal adherence rates. Patient-centered approaches exploiting mobile phone communications (mHealth) have been shown to improve adherence to cART and promote achievement of suppressed HIV plasma viral loads. However, data are scarce on the health care provider (HCP) time commitments and health care costs associated with such interventions. This knowledge is needed to inform policy and programmatic implementation. OBJECTIVE The purpose of this study was to approximate the resources required and to provide an estimate of the costs associated with running an mHealth intervention program to improve medication adherence in people living with HIV (PLWH). METHODS This prospective study of HCP utilization and costs was embedded within a repeated measures effectiveness study of the WelTel short-message service (SMS) mHealth program. The study included 85 vulnerable, nonadherent PLWH in Vancouver, Canada, and resulted in improved medication adherence and HIV plasma viral load among participants. Study participants were provided mobile phones with unlimited texting (where required) and received weekly bidirectional text messages to inquire on their status for one year. A clinic nurse triaged and managed participants' responses, immediately logging all patient interactions by topic, HCP involvement, and time dedicated to addressing issues raised by participants. Interaction costs were determined in Canadian dollars based on HCP type, median salary within our health authority, and their time utilized as part of the intervention. RESULTS Participant-identified problems within text responses included health-related, social, and logistical issues. Taken together, management of problems required a median of 43 minutes (interquartile range, IQR 17-99) of HCP time per participant per year, for a median yearly cost of Can $36.72 (IQR 15.50-81.60) per participant who responded with at least one problem. The clinic nurse who monitored the texts solved or managed 65% of these issues, and the remaining were referred to a variety of other HCPs. The total intervention costs, including mobile phones, plans, and staffing were a median Can $347.74/highly vulnerable participant per year for all participants or Can $383.18/highly vulnerable participant per year for those who responded with at least one problem. CONCLUSIONS Bidirectional mHealth programs improve HIV care and treatment outcomes for PLWH. Knowledge about the HCP cost associated, here less than Can $50/year, provides stakeholders and decision makers with information relevant to determining the feasibility and sustainability of mHealth programs in a real-world setting. CLINICALTRIAL ClinicalTrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/70IYqKUjV).

BackgroundImproving adherence to combined antiretroviral therapy (cART) can be challenging, especially among vulnerable populations living with HIV. Even where cART is available free of charge, social determinants of health act as barriers to optimal adherence rates. Patient-centered approaches exploiting mobile phone communications (mHealth) have been shown to improve adherence to cART and promote achievement of suppressed HIV plasma viral loads. However, data are scarce on the health care provider (HCP) time commitments and health care costs associated with such interventions. This knowledge is needed to inform policy and programmatic implementation. ObjectiveThe purpose of this study was to approximate the resources required and to provide an estimate of the costs associated with running an mHealth intervention program to improve medication adherence in people living with HIV (PLWH). MethodsThis prospective study of HCP utilization and costs was embedded within a repeated measures effectiveness study of the WelTel short-message service (SMS) mHealth program. The study included 85 vulnerable, nonadherent PLWH in Vancouver, Canada, and resulted in improved medication adherence and HIV plasma viral load among participants. Study participants were provided mobile phones with unlimited texting (where required) and received weekly bidirectional text messages to inquire on their status for one year. A clinic nurse triaged and managed participants' responses, immediately logging all patient interactions by topic, HCP involvement, and time dedicated to addressing issues raised by participants. Interaction costs were determined in Canadian dollars based on HCP type, median salary within our health authority, and their time utilized as part of the intervention. ResultsParticipant-identified problems within text responses included health-related, social, and logistical issues. Taken together, management of problems required a median of 43 minutes (interquartile range, IQR 17-99) of HCP time per participant per year, for a median yearly cost of Can $36.72 (IQR 15.50-81.60) per participant who responded with at least one problem. The clinic nurse who monitored the texts solved or managed 65% of these issues, and the remaining were referred to a variety of other HCPs. The total intervention costs, including mobile phones, plans, and staffing were a median Can $347.74/highly vulnerable participant per year for all participants or Can $383.18/highly vulnerable participant per year for those who responded with at least one problem. ConclusionsBidirectional mHealth programs improve HIV care and treatment outcomes for PLWH. Knowledge about the HCP cost associated, here less than Can $50/year, provides stakeholders and decision makers with information relevant to determining the feasibility and sustainability of mHealth programs in a real-world setting. Trial RegistrationClinicalTrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/70IYqKUjV).

Background Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure. Methods HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period. Results At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL. Conclusions Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding.

Objective To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24 months. Design Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5 mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24 months. Adverse events were recorded throughout. Results Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38 years (IQR 32–45, range 15–66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL 3 (376–695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74–3.05 fold higher peak antibody response compared to those without ( p from 0.006 to Conclusions This study is the first to examine the qHPV vaccine in HIV-positive women out to 24 months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination. Clinical trial registration: http://www.isrctn.com/ISRCTN33674451

Objective This guideline reviews the evidence relating to the care of pregnant women living with HIV and the prevention of perinatal HIV transmission. Prenatal care of pregnancies complicated by HIV infection should include monitoring by a multidisciplinary team with experts in this area. Outcomes Outcomes evaluated include the impact of HIV on pregnancy outcome and the efficacy and safety of antiretroviral therapy and other measures to decrease the risk of vertical transmission. Evidence Published literature was retrieved through searches of PubMed and The Cochrane Library in 2012 and 2013 using appropriate controlled vocabulary (HIV, anti-retroviral agents, pregnancy, delivery) and key words (HIV, pregnancy, antiretroviral agents, vertical transmission, perinatal transmission). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to June 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Resume Objectif La presente directive clinique passe en revue les donnees probantes traitant des soins a offrir aux femmes enceintes vivant avec le VIH et de la prevention de la transmission perinatale du VIH. Les soins prenataux a offrir dans le cadre de grossesses compliquees par une infection par le VIH devraient comprendre un suivi mene par une equipe multidisciplinaire comptant des specialistes du domaine. Issues Parmi les issues evaluees, on trouve l'effet du VIH sur l'issue de la grossesse, ainsi que l'efficacite et l'innocuite du traitement antiretroviral, et celles d'autres mesures visant a attenuer le risque de transmission verticale. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans PubMed et The Cochrane Library en 2012 et en 2013 au moyen d'un vocabulaire controle (p. ex. « HIV », « anti-retroviral agents », « pregnancy », « delivery ») et de mots cles (p. ex. « HIV », « pregnancy », « antiretroviral agents », « vertical transmission », « perinatal transmission ») appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles rediges en anglais ou en francais. Aucune restriction n'a ete imposee en matiere de date. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en juin 2013. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales Valeurs La qualite des resultats est evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1)

BACKGROUND: HIV exposed, uninfected (HEU) children have higher incidences of neurodevelopmental delay and diagnoses, largely attributed to social determinants that impact their families. In Canada, the majority of mothers living with HIV have experienced significant trauma, and are more likely than the general population to be new to Canada, Indigenous, have a history of IV drug use or incarceration. In a provincial women-and-family-centered HIV clinic, after noticing that many HEUs did not attend recommended early interventions or developmental services despite regular pediatric care and social work support, the following strategies were initiated in 2014: developmental screening every 3–6 months until school age, early referral to interventions, and documentation of referral progress. OBJECTIVES: This quality assurance review aims to characterize the effects of strategies implemented in 2014, and the current developmental needs of HEUs in terms of access to interventions. DESIGN/METHODS: A retrospective chart review was performed for 169 HEUs, born 2008–2016, with ≥1 clinic visit. Developmental screens, referrals, demographics, and social factors were collected. The adverse childhood experiences (ACE) score was used to measure childhood trauma. HEUs were divided into older/younger cohorts depending on whether they were 18 months of age before/after 2014. RESULTS: All 169 HEUs were screened for developmental delay at nearly every visit, with 45.6% and 42.9% of the younger and older cohort screening positive at some point before the age of 5. A higher proportion of delayed children successfully connected with an early intervention service after 2014 (88.5% vs 63.3%). Of those 5 or older at the time of the study with continued follow-up (50.8%), 33.3% have a developmental diagnosis requiring support at school. The majority had ACEs: 70.4% had ≥1, 9.5% had ≥4. Child protective services (CPS) were involved in 37.3%, 37.8% had financial instability, and 17.1% had housing instability. Developmental concerns were documented in the majority of socially vulnerable HEUs, including those who had CPS involvement (71.4%), ACE ≥4 (78.6%), financial instability (61.3%), and housing instability (71.4%). Smaller proportions of HEUs without these social vulnerabilities had developmental concerns: no CPS involvement (28.3%), ACE

Objective To evaluate the birth rates of women living with HIV (WLWH) compared to the general population in British Columbia (BC), Canada. Methods We retrospectively reviewed clinical and population level surveillance data from 1997 to 2015. Live birth rates from 1997 to 2015 among WLWH aged 15–49 years were compared with those of all BC women. Next, the number of live births among WLWH with a live birth between 1997–2012 and HIV-negative controls matched 1:3 by geocode were compared. Results WLWH had a lower birth rate compared to all BC women [31.4 (95%CI, 28.6–34.3) vs. 40.0 (39.3–40.1)/1000 person years]. Stratified by age, WLWH aged 15–24 years had a higher birth rate while WLWH aged 25–49 years had a lower birth rate than BC women (p

Introduction The objective of this study was to evaluate a provincewide program designed to identify HIV infection accurately and to prevent mother to child transmission among high-risk pregnant women of unknown serostatus. Methods Between 2000 and 2007, 347 high-risk women were identified through the Prevention of Mother to Child Transmission (PMTCT) program implemented in 27 hospitals across British Columbia. Rates of HIV transmission and details of the implementation of prophylaxis kits were assessed. Results Of the 346 high-risk mother-infant pairs identified and included in the provincial program, 35.4% of the mothers and 95.7% of infants received antiretroviral therapy for prevention of vertical transmission. Of 309 pairs who subsequently underwent HIV testing, five mothers were found to be HIV positive, an infection rate of 16.2/1000 in this cohort; the overall rate in BC is 0.68/1000 births. One of the five infants born to an HIV positive mother was infected with HIV. Discussion The program was successful in identifying a subgroup of pregnant women at increased risk of HIV infection; however, mother to child transmission occurred in one of five cases (20%). To reduce the risk of mother to child HIV transmission in BC to the lowest possible level, additional strategies such as increasing uptake of prenatal screening and point-of-care testing in labour and delivery may need to be explored.

The standard of care for the prevention of vertical transmission (VT) of HIV in Canada and other developed countries includes routine prenatal HIV testing for all pregnant women, and for those testing positive: antepartum combination antiretroviral therapy (cART); intrapartum intravenous zidovudine; six weeks of postnatal oral zidovudine to the infant; and exclusive formula feeding of the infant. With these interventions, the rate of VT has been reduced from 25% to 40%, to 4 weeks before delivery. The purpose of the present article is to highlight recent changes in management guidelines and important caveats to these changes with regard to prevention of VT in the Canadian context. There is a global trend to replace the use of the previous conventional terminology of ‘mother-to-child transmission’ with ‘vertical transmission’ or ‘perinatal transmission’ to remove implications of blame from the mother. In the present article, ‘vertical transmission’ is used throughout. HIV testing during pregnancy HIV testing is recommended for all pregnant women in Canada, with appropriate pre- and post-test counselling. Women whose HIV status is unknown at the time of delivery should undergo rapid HIV antibody testing. For women at increased risk for HIV infection (eg, intravenous drug use, commercial sex work, frequent unprotected intercourse with multiple partners, HIV-negative woman of a serodiscordant couple) who test negative early in pregnancy, repeat testing late in pregnancy (beginning of the third trimester) and at delivery is strongly encouraged. When such women present in labour, advice regarding maternal HIV diagnosis and management should be sought from obstetric and adult HIV experts on an urgent basis; similarly, pediatric HIV experts should be consulted regarding infant management in such situations. Women living with HIV, either previously diagnosed or identified during pregnancy, should be followed by a specialist with expertise in the management of HIV during pregnancy, treated with cART and monitored for viral suppression. Prelabour elective Cesarean section delivery should be planned for those not on cART and/or anticipated or documented to have inadequate viral suppression near delivery (viral load >1000 copies/mL). For women who were previously diagnosed with HIV in whom viral load is not documented to be fully suppressed in the four weeks preceding onset of labour and for women diagnosed with HIV infection at the time of labour, urgent consultation with adult and pediatric HIV experts and an obstetrician with expertise in the management of HIV is essential. Recommendation 1: Pediatricians and other health care providers involved in the care of HIV-infected pregnant women and their children should advocate for universal HIV testing of all pregnant women with appropriate pre- and post-test counselling so that appropriate preventive measures can be implemented in a timely manner. When this fails, testing of the mother at delivery, or of the infant if maternal testing is not possible, should be ensured. Ideally, no infant should be discharged from hospital without the HIV status of the mother being known. Pediatricians and family physicians who perform routine neonatal examinations should verify that the HIV status of the mother or child is known and documented. Recommendation 2: Urgent consultation with an obstetrician with HIV expertise and an adult HIV expert is recommended for diagnosis and management of women deemed to be at high risk for HIV infection with unknown status at the time of labour. Similarly, a pediatric HIV expert should be consulted regarding infant management in such situations.

OBJECTIVE. Our intent was to investigate the neurodevelopment of HIV-uninfected children exposed to combination highly active antiretroviral therapy in pregnancy compared with children not exposed to highly active antiretroviral therapy but with similar socioeconomic backgrounds. PATIENTS AND METHODS. A prospective controlled cross-sectional study of the neurodevelopment of children exposed to highly active antiretroviral therapy versus those not exposed was performed by using the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales at 18 to 36 months of age. The highly active antiretroviral therapy–exposed children were born to HIV-infected women but were uninfected themselves. The control children were born to HIV-uninfected women with similar anticipated socioeconomic background (hepatitis C infected and high proportion of substance use). Sociodemographic, clinical, highly active antiretroviral therapy (antenatal, intrapartum, neonatal), and substance-use histories were collected. Results were compared by using analyses of covariance and χ2 analysis. RESULTS. Thirty-nine highly active antiretroviral therapy–exposed and 24 control children were assessed. All mean scores were lower for those in the highly active antiretroviral therapy–exposed group than those in the control group (Bayley Mental Development Index: 85.4 vs 94.3; Bayley Psychomotor Development Index: 93.4 vs 96.6; Vineland mean communication score: 90.1 vs 94.4; Vineland mean daily-living score: 91.2 vs 93.6; Vineland mean socialization score: 97.1 vs 98.4). However, when maternal substance use during pregnancy was controlled for, there were no significant differences between the groups in any domains assessed. Children in both groups exposed to maternal substance use scored significantly lower than children not exposed in all domains except communication skills. It is important to note that there were no differences between the highly active antiretroviral therapy–exposed children with no substance exposure and the control children with no substance exposure in any of the scores. CONCLUSIONS. HIV- and highly active antiretroviral therapy–exposed HIV-uninfected children had lower development and adaptive behavior scores when compared with children who had not been exposed. However, these differences were not significant after correcting for maternal substance use, which had a greater impact on neurodevelopment than highly active antiretroviral therapy exposure. These results suggest that perinatal highly active antiretroviral therapy exposure is not associated with altered development and behavior at 18 to 36 months of age.

To investigate potential mitochondrial toxicity in HIV-uninfected infants exposed to highly active antiretroviral therapy (HAART) in utero and/or neonatal zidovudine.A prospective observational study performed in a tertiary referral center for HIV-infected women and their infants and children.Plasma lactate was measured repeatedly during the first 6 months of life in a consecutive cohort of infants exposed to HAART in utero and/or neonatal zidovudine. Maternal CD4, HIV RNA concentration, antiretroviral and substance use histories, mode of delivery, infant gender, cord pH, Apgar score and birth weight were collected.The plasma lactate was above normal on at least 1 occasion in 35 of 38 (92%) infants and reached levelsor =5 mmol/l in 10 (26%) infants. Overall 78 of 117 (68%) lactate measurements were elevated, with 11 (10%) in the serious (or =5 mmol/l) range. None of the infants received antiretrovirals beyond 6 weeks, yet elevated lactates persisted up to age 6 months. Two infants had reversible symptoms consistent with those of lactic acidemia. No association was found between the infant peak lactate and the type of therapy during pregnancy, its duration or maternal substance use.Transient lactic acidemia was observed in the majority of HIV uninfected infants exposed to HAART in utero and/or zidovudine neonatally. We hypothesize that the hyperlactatemia is a consequence of persistent, primarily subclinical, mitochondrial toxicity from the transplacental and neonatal exposure to antiretrovirals and of impaired hepatic lactate clearance. Although the clinical relevance of our findings is unknown, we recommend lactate monitoring in these infants, considering discontinuation of neonatal zidovudine in symptomatic infants with lactateor =5 mmol/l and careful long term follow up of these children.

Background: Combination antiretroviral therapy (cART) as treatment for human immunodeficiency virus (HIV) infection is effective and available, but poor medication adherence limits benefits, particularly in vulnerable populations. In a Kenyan randomized controlled trial, a weekly text-messaging intervention (WelTel) improved cART adherence and HIV viral load (VL). Despite growing evidence for short message service (SMS) text-message interventions in HIV care, there is a paucity of data utilizing these interventions in marginalized or female cohorts. Objective: This study was undertaken to assess whether the standardized WelTel SMS text-message intervention applied to a vulnerable, predominantly female, population improved cART adherence and VL. Methods: We conducted a repeated measures study of the WelTel intervention in high-risk HIV-positive persons by measuring change in VL, CD4 count, and self-reported adherence 12 months before and 12 months after the WelTel intervention was introduced. Inclusion criteria included VL ≥200 copies/mL, indication for treatment, and meeting vulnerability criteria. Participants were given a mobile phone with unlimited texting (where required), and weekly check-in text messages were sent for one year from the WelTel computer platform. Clinical data were collected for control and intervention years. Participants were followed by a multidisciplinary team in a clinical setting. Outcomes were assessed using Wilcoxon signed ranks tests for change in CD4 and VL from control year to study end and mixed-effects logistic regressions for change in cART adherence and appointment attendance. A secondary analysis was conducted to assess the effect of response rate on the outcome by modeling final log10 VL by number of responses while controlling for mean log10 VL in the control year. Results: Eighty-five participants enrolled in the study, but 5 withdrew (final N=80). Participants were predominantly female (90%, 72/80) with a variety of vulnerabilities. Mean VL decreased from 1098 copies/mL in the control year to 439 copies/mL at study end (P=.004). Adherence to cART significantly improved (OR 1.14, IQR 1.10-1.18; P

In children born to immunocompetent women, congenital toxoplasmosis almost always results from primary infection during pregnancy. However, reactivation of latent toxoplasmosis during pregnancy could occur in HIV-infected pregnant women, particularly in those who are severely immunocompromised, and result in maternal-fetal transmission of the parasite. This mode of infection has been described in case reports but the risk of transmission is unknown. Findings on toxoplasmosis are presented from the European Collaborative Study, a prospective study of children born to women known to be HIV-infected at the time of delivery. In 1058 children followed for a mean duration of 35 months, only one child developed clinical toxoplasmosis. This child was HIV-infected, severely immunocompromised, and acquired toxop]asmosis postnatally. Congenital infection was excluded serologically in a subgroup of 167 children, of whom an estimated 71 had been at risk of infection. These clinical and serological findings indicate a low general risk of maternal-fetal transmission of Toxoplasma infection in HIV-infected women. It is not possible to draw conclusions about the risk of transmission for severely immunocompromised HIV-infected women because most women in the study were asymptomatic.

OBJECTIVES HIV disease can lead to accelerated telomere attrition, although certain drugs used as part of antiretroviral therapy (ART) can inhibit telomerase reverse transcriptase activity. This could in turn lead to shorter telomeres. We hypothesized that HIV and ART exposure would be associated with shorter leukocyte telomere length (TL) in exposed mother/infant pairs compared with controls. METHODS In these retrospective and prospective observational cohort studies, TL was evaluated in peripheral blood leukocytes obtained from HIV-infected pregnant women treated with ART and their uninfected infants, and compared with HIV untreated (retrospective cohort) or HIV mothers and their infants (prospective cohort). RESULTS In HIV-infected ART-exposed mothers, leukocyte TL was not significantly shorter than that in HIV untreated mothers or HIV controls, nor was their infants' TL significantly different. Cord blood of ART-exposed infants exhibited TL shorter than that from infants born to HIV-negative mothers. Placenta also showed evidence of shorter TL after adjustment for relevant covariates. Factors associated with shorter maternal and infant TL included smoking and the use of drugs of addiction in pregnancy. CONCLUSIONS These results suggest that maternal HIV infection or exposure to ART has minimal effect on infant leukocyte TL, a reassuring finding. In contrast, tissues that express higher telomerase activity such as umbilical cord blood and placenta appear comparatively more affected by ART. Smoking and the use of drugs of addiction have a negative impact on maternal and infant leukocyte TL, possibly through oxidative telomere damage.

OBJECTIVES Nucleo(s/t)ide reverse transcriptase inhibitors given to HIV-infected pregnant women to prevent vertical transmission may adversely affect mitochondrial DNA (mtDNA). We hypothesized that HAART-exposed/HIV-uninfected infants may show higher blood mtDNA mutation burden than controls born to HIV-uninfected mothers. METHODS Blood was collected from in-utero HIV/HAART-exposed infants and controls, as well as from a subset of their mothers. The presence of mtDNA A→C/T→G (AC/TG) mutations was measured by cloning and sequencing D-loop PCR amplicons. Relationships with maternal characteristics were examined. RESULTS No significant difference was found between the percentage of HIV/HAART-exposed infants with AC/TG mutations (N = 15/57, 26.3%) and controls (N = 10/70, 14.3%) before (P = 0.090) or after controlling for covariates (P = 0.058), although a tendency was observed. However, significantly more HIV/HAART-exposed mothers (N = 18/42, 42.9%) harboured AC/TG mutations compared with controls (N = 7/39, 17.9%) before (P = 0.015) and after (P = 0.012) controlling for covariates. AC/TG mutations were more prevalent in HIV/HAART-exposed mothers than in their infants (N = 42, 42.9 vs. 23.8%, P = 0.033), however, this difference disappeared after controlling for covariates. No difference was seen between control mothers and their infants (N = 39, both 17.9%). In HIV/HAART-exposed mothers, only a detectable HIV plasma viral load near delivery predicted AC/TG mutations. CONCLUSION Our results suggest that HIV and/or HAART exposure are associated with increased prevalence of AC/TG mtDNA mutations in mothers and show a similar tendency in infants exposed during pregnancy. As accumulation of mtDNA mutations has been linked with aging and age-associated diseases, this may raise concerns in the long term for HIV and HAART-exposed populations.

L’endoscopie est consideree comme un examen de choix dans l’evaluation et parfois meme le traitement de certaines manifestations gastro-intestinales de l’infection HIV de l’adulte. L’experience pediatrique, meme si elle reste encore limitee dans ce domaine, semble confirmer le role preponderant de l’endoscopie dans la recherche d’un diagnostic etiologique en presence de symptomes œsophagiens, d’agents infectieux et de signes de dysfonctionnement intestinal en cas de diarrhee chronique, manifestations gastro-intestinales les plus frequentes de l’infection HIV chez l’enfant. Cet examen n’en demeure pas moins invasif, non denue de risque, notamment infectieux chez ces enfants immunodeprimes. Il reste reserve aux situations ou un diagnostic precis est necessaire en presence de manifestation gastro-intestinale severe.

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.

The qualitative and quantitative performance of a human immunodeficiency virus type 1 (HIV-1) whole blood culture method was assessed for use in the diagnosis of vertical HIV-1 infection. This method requires < 1 mL of whole blood and allows for the quantification of blood virus load. HIV-1 was isolated from 36 (95%) of 38 whole blood specimens from 27 HIV-1-infected children compared with 0 of 16 whole blood specimens from 16 uninfected children. HIV-1 titers were significantly higher in severely symptomatic children (2450 TCID/mL) than in less symptomatic children (179 TCID/mL). This simple quantitative culture assay may be useful for the early diagnosis of vertical HIV-1 infection, the assessment of blood virus load, and the evaluation of antiretroviral therapies.

Background. HIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study. Methods. In four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once. Findings. Nine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or 'tolerated' the virus. Interpretation. The detection of virus or viral DNA in 'uninfected' children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.

Objective: To validate the technique of HIV-1 culture from whole blood for the quantitation of viral load in infected children. Patients: Forty-three HIV-1-infected children were followed in two paediatric centres. Methods: Quantitative HIV-1 cultures from unfractionated whole blood using an end-point dilution technique were compared with simultaneous quantitative cultures of peripheral blood mononuclear cells (PBMC) and plasma. Results: Good sensitivity (93%) of the methods used was confirmed. A close correlation (r = 0.80) was observed between HIV-1 titres measured directly from whole blood and those expected from PBMC and plasma titres. The mean whole blood viral load was higher in patients with more severe signs of disease, but the difference did not reach statistical significance. The whole blood viral titres measured sequentially at monthly intervals remained within one dilution of each other in 16 of the 22 patients studied. Conclusion: In this study, the quantitation of HIV-1 in unfractionated blood allowed for a reliable and sensitive measurement of the whole blood viral load in infected children.

Thirty-three infants born to human immunodeficiency virus type 1 (HIV-1)-seropositive women were evaluated from birth using plasma and peripheral blood mononuclear cell (PBMC) cultures, polymerase chain reaction, and serum p24 antigen assays. Five children were identified as infected. Evidence of infection was found in cord blood and subsequent samples from 2 infected children, suggesting in utero infection. Virologic studies on cord blood and early neonatal specimens from the 3 other infected children were negative but became positive by 8 weeks of age, suggesting either intrapartum transmission or sequestration of virus with subsequent detection. An increase in blood (plasma and PBMC) virus titers consistent with primary viremia was observed in 4 infants between 3 and 16 weeks of age. Blood virus titers subsequently declined in the absence of antiretroviral therapy and in the absence of activated HIV-1-specific cytotoxic T lymphocyte responses or broadly neutralizing antibodies. Confirmation of these results in larger studies may be helpful in the design of clinical trials to interrupt vertical transmission or to modify the course of infection.