Attention and neurodevelopment in young children who are HIV-exposed uninfected.

ABSTRACTChildren HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment.

Neurodevelopment of HIV-exposed uninfected children compared with HIV-unexposed uninfected children during early childhood.

HIV-exposed uninfected (HEU) children during the preschool and early school ages may be at-risk for neurodevelopmental challenges due to in utero and perinatal exposure to HIV and/or antiretroviral (ARV) medications. HEU children and HIV-unexposed uninfected (HUU) children from the community were recruited and tested at 3 to 4 and 5 to 6 years of age. Demographic information, HIV/ARV exposure and measures of intelligence, visuomotor skills, and adaptive functioning were obtained. Nonparametric tests assessed group differences and multiple regression analyses adjusted for demographic variables. Additional multiple regression analyses were performed within the HEU group to investigate associations between neurodevelopmental measures and variables of HIV/ARV exposure. At 3 to 4 years, 211 HEU children and 31 HUU children were assessed, and 144 HEU children and 58 HUU children were assessed at 5 to 6 years of age. At 3 to 4 years of age, HEU children scored significantly lower on measures of Full-Scale IQ, Performance IQ, visual motor integration, and adaptive functioning. At 5 to 6 years of age, HEU children scored significantly lower on all neurodevelopmental measures. At both ages, children who were female and those with mothers who were employed achieved higher scores on measures intellectual ability and/or adaptive functioning. Within the HEU group, no consistent associations were found between neurodevelopmental measures and HIV/ARV specific variables. HEU children demonstrated significantly lower scores on neurodevelopmental measures than HUU children during early childhood. Gaps in verbal intellectual abilities were identified with age, highlighting the importance of monitoring neurodevelopment in this population over time. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Early academic achievement of HIV-exposed uninfected children compared to HIV-unexposed uninfected children at 5 years of age.

HIV-exposed uninfected (HEU) children may be at-risk for poorer academic achievement compared to HIV-unexposed uninfected (HUU) children due to in utero and perinatal exposure to HIV and/or anti-retroviral (ARV) medication. Understanding the risk factors for academic underachievement is important for implementing timely intervention and academic supports. HEU (N = 110, mean (SD) age 5.59 (0.22) years) and HUU (N = 43, mean (SD) age 5.73 (0.64) years) children completed assessments of general intelligence (WPPSI-III) and academic achievement (WRAT-4). Parent interviews and medical record reviews were used to obtain sociodemographic and maternal health data. HUU children scored significantly higher than HEU children on single word reading (p = 0.006), math calculation skills (p = 0.003), Verbal IQ, Performance IQ, Full Scale IQ, and Processing Speed (all WPPSI-III measures p < 0.001). Verbal IQ at 3-4 years predicted academic achievement at 5-6 years of age, yet sociodemographic and medical factors did not. These findings demonstrate that HEU children obtained significantly lower scores of intellectual, reading, and math abilities during early childhood. Addressing these early gaps before HEU children enter primary school will be critical for optimizing their learning and academic potential.

The relationship between stigma and a rehabilitation framework [international classification of functioning, disability and health (ICF)]: three case studies of women living with HIV in Lusaka, Zambia.

PURPOSE: To explore how the International Classification of Functioning, Disability and Health, a rehabilitation framework, can provide a holistic understanding of stigma experiences of three women living with human immunodeficiency virus in Lusaka, Zambia. METHODS: A secondary analysis of three cases by drawing on interview transcripts collected as part of a larger longitudinal study with eighteen women living with the virus. The interview tool used the rehabilitation framework to ask questions about the impact of the virus on the body, daily activities, social participation and the future. Vignettes were produced for each of the eighteen women including information on stigma and the rehabilitation framework. Three case studies were developed from women who provided comprehensive accounts of stigma and the International Classification of Functioning, Disability and Health. RESULTS: Stigma experiences aligned well with three dimensions of the International Classification of Functioning, Disability and Health: participation restrictions, environmental and personal factors. These domains were used to understand stigma in three forms (i.e. enacted, self and structural stigma) as experienced by these women. CONCLUSIONS: More research is needed to ascertain how stigma and rehabilitation are related in other environments and populations and to explore how to mitigate stigma within the rehabilitation context.IMPLICATIONS FOR REHABILITATIONRehabilitation professionals deal with aspects of stigma and discrimination in their clinical work and this analysis offers a way to consider HIV-related stigma within rehabilitation in an organized and theoretically-informed way.The insights from this study are important for the field of HIV and for advancing understanding of the complexities of stigma in the context of rehabilitation more broadly.This analysis offers guidance to rehabilitation providers about the nuanced and multi-faceted ways that stigma can occur in the context of rehabilitation, including within their own clinical practice.

Clinical Correlates of Human Immunodeficiency Virus-1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years.

BACKGROUND: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. METHODS: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). RESULTS: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). CONCLUSIONS: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.

Knowledge and awareness of Human Papillomavirus (HPV) and HPV vaccines among Caribbean youth: the case of the Bahamas.

There is a high burden of cervical cancer in the Caribbean region, particularly in the Bahamas, yet there are few studies of Human Papillomavirus (HPV) and HPV vaccine in the region. The objective of this study was to assess the knowledge and awareness of HPV and the HPV vaccine among school-aged youth (15-18 years) living in the Bahamas.Cross-sectional data were obtained from the "Getting to Zero" HIV study in the Bahamas conducted in 2014/2015 (n = 1553). The questionnaire elicited information on knowledge of HPV and HPV vaccines, using previously validated scales. Data analysis included Chi-square tests and Mann Whitney U test.In this sample of school-aged youth, only 10.7% (146/1364) had ever heard of HPV. With respect to those who were sexually active (n = 685), only 10.7% had ever heard of HPV. For those who had heard of HPV, knowledge of HPV and HPV vaccines was assessed on an HPV Knowledge and HPV Vaccine Knowledge scale, respectively. There was no statistically significant difference in mean HPV knowledge score between males and females, or HPV vaccine knowledge scores, between males and females.There was a general lack of awareness of HPV and HPV vaccines among school-aged youth in the Bahamas. This is an important gap in the HPV vaccine strategy and cancer prevention, as this is the age at which most people acquire HPV. It emphasizes the importance of developing a careful implementation plan, with an evaluation of knowledge and attitudes, in order to have an effective HPV vaccine uptake.

"Getting to Zero New HIV Infections in the Caribbean": Knowledge and Attitudes Toward Male Circumcision Among Adolescent Males in The Bahamas.

Male circumcision (MC) plays a significant role in reducing new HIV infections, particularly in high prevalence countries. This cross-sectional study assesses the prevalence of MC and attitudes toward MC among youth aged 15-18 years in The Bahamas, a medium HIV prevalence country. The survey included 797 young men who completed a questionnaire on MC. Data analyses included chi-squared tests. The self-reported prevalence of MC among youth was 16.7% (121/759). Most of the circumcised youth were circumcised as infants, 84% (107/121) were pleased with their circumcision, and 71% would recommend it to others. For uncircumcised youth, 35% (189/533) would consider voluntary male circumcision (VMC) and 26% would recommend MC to others. In all scenarios, circumcised youth were more likely to be positive about MC. Among uncircumcised young men, being older (17-18 years compared to 15-16 years) was the only variable statistically associated with considering MC or recommending MC. After being presented with information on the benefits of MC for HIV prevention, the number of men who were positive about MC increased. Most of the young men in this cohort would consider VMC for reducing HIV incidence. Also, many stated that, if they had a male child, they would have him circumcised. The attitudes of these youth emphasize the need to provide information on HIV in addition to general health benefits of MC if there were to be a sustainable MC program within this population.

The conceptualization of stigma within a rehabilitation framework using HIV as an example.

Stigma theory is concerned with inclusion and opportunities that influence well-being. Rehabilitation is also concerned with social inclusion and well-being. This is a central concern in one of the leading rehabilitation theories, the World Health Organization's International Classification of Functioning, Disability and Health. Despite these shared concerns, the relationship between the fields of stigma and rehabilitation has not been well theorized to date. Using human immunodeficiency virus (HIV) as an example, this article presents an analysis of three ways that stigma may be conceptualized within the context of the International Classification of Functioning, Disability and Health. Three broad spheres of stigma are described: enacted, self, and structural stigma. These three forms of stigma are then aligned in unique ways with three particular constructs of the International Classification of Functioning, Disability and Health: participation restrictions, environmental, and personal contextual factors. This conceptualization illustrates how rehabilitation professionals and other practitioners, policy makers and researchers can better understand the dynamic and nuanced forms of stigma and how they relate to rehabilitation. Implications for rehabilitation This article enables rehabilitation professionals to better understand stigma as it relates to rehabilitation and human immunodeficiency virus. Rehabilitation professionals have the important job of allies and advocates for persons experiencing restrictions in these domains as a result of stigma.

Longitudinal development of cognitive, visuomotor and adaptive behavior skills in HIV uninfected children, aged 3-5 years of age, exposed pre- and perinatally to anti-retroviral medications.

Little is known about the neurodevelopmental outcomes of children older than 3 years of age born to HIV infected mother but who are HIV-uninfected (HEU), and who have been exposed in utero and early in life to HIV and to antiretroviral medications (ARVs). We conducted a longitudinal study of cognitive, visuomotor and adaptive function of HEU children, who were assessed at two ages, 3.5 and 5.5 years. Sixty-four children (33 female) were assessed. In comparison with population norms for their age, at 3.5 years of age they had scores significantly below age expectations on aspects of adaptive behavior, but at age 5.5 years, their scores did not significantly diverge from the population norms on any of the measures. Verbal intelligence was lower at age 5.5 than at age 3.5 years, although there were also improvements in some features of adaptive behavior. Exposure to PI-based ARVs (compared to NNRTIs) was associated with higher Performance IQ, visuomotor and communication scores at age 5.5 years. Birth, early growth, and sociodemographic variables were predictive of outcomes. This study is important in tracking the trajectory of neurocognitive development across the pre-school and early school age years. The findings suggest that the full impact of early ARV exposure may not be evident until a considerable period of development has occurred. The results raise the possibility of negative effects of early ARV exposure on neurodevelopment that emerge over time, and reiterate the importance of sociodemographic and early health variables for optimal development.

Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission.

BACKGROUND: Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen. METHODS: Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3-8 mg/L]. RESULTS: Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32-41 weeks) and 2.9 kg (1.5-4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6-25.1 mg/L), 3.5 mg/L (1.6-6.8 mg/L), and 4.3 mg/L (0.1-19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg·h (0.01-0.50 L·kg·h) at week 2 to 0.18 L·kg·h (0.01-0.78 L·kg·h) at week 4. Increased drug exposure [area under the curve (AUCτ)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%). CONCLUSIONS: Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.

Childhood exposures to discarded needles and other objects potentially contaminated with blood-borne pathogens in Toronto, Canada.

BACKGROUND: Exposure to discarded needles or other objects put children at risk for infection with blood-borne pathogens (BBP), including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C. OBJECTIVE: The purpose of this study was to retrospectively analyze the epidemiology, management and outcome of children following such exposures in the greater Toronto community setting. METHODS: A retrospective study of children <19 years of age who had community-based exposure to objects that could contain BBP between January 2001 and December 2014. Sexual and hospital inpatient exposures were excluded. Patients were identified by medical record review of all children who had HIV testing performed. RESULTS: Sixty-six community-based exposures to objects potentially contaminated with BBP were identified (71.2% needlesticks). The median age was 6.3 years (interquartile range 3.8, 7.8). Exposures occurred outdoors in the community (45.5%), in schools (30.3%), homes (15.2%) and community/outpatient clinics (9.0%). Of 11 (16.7%) identified source subjects, 7 were known to be HIV infected. HIV post-exposure prophylaxis was prescribed to 22 (33.3%) children; 15 (71.4%) completed the course. Only 41.2% of previously unvaccinated children were documented to have completed a full HBV vaccine series post-exposure. No blood-borne infections were documented, but only 60.6% had documentation of adequate follow-up testing. CONCLUSIONS: Enhanced public health interventions in schools and other community settings are needed to reduce childhood risk of exposure to needlesticks or other objects potentially contaminated with BBP.

Lentiviral expression system for the purification of secreted proteins from human cell cultures.

BACKGROUND: Recombinant proteins of therapeutic use are ideally produced in human cells to ensure appropriate co- and post-translational modifications. However, purification of secreted proteins from the culture media is impeded by low expression from transfected cell lines and the presence of serum proteins. Here we describe a simple and cost-effective approach based on lentiviral vector-mediated gene delivery and expression of a secreted His-tagged protein from human embryonic kidney 293 T cells and direct affinity chromatography purification from the cell culture media. RESULTS: Using a protein-based HIV entry inhibitor, soluble CD4 (sCD4), we demonstrated that 293 T cells transduced with a lentiviral vector mediated over 10-fold higher secretion of sCD4 in comparison to 293 T cells transfected with the corresponding plasmid. Secretion of sCD4 increased with the dose of the lentiviral vector up to a multiplicity of infection of 50. Exchanging the native signal peptide of sCD4 with the signal peptide of human alpha-1 antitrypsin increased expression by 50 %. There was no difference in expression from a monocistronic or bicistronic lentiviral vector. Reduction of the serum concentration in the culture media had no significant effect on the secretion of sCD4. Small-scale purification from 50 ml of culture media with reduced serum content yielded up to 1 mg of pure sCD4. Purified sCD4 bound to recombinant HIV envelope glycoprotein 120 (Env gp120) and inhibited HIV entry at concentrations comparable to published results. CONCLUSION: The procedure outlined in this study can be performed without the need for specialized reagents or equipment and could easily be adapted by any laboratory. Furthermore, the method could be used to produce sCD4 fusion proteins or other His-tagged proteins.

Safety of combination antiretroviral prophylaxis in high-risk HIV-exposed newborns: a retrospective review of the Canadian experience.

INTRODUCTION: The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. METHODS: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. RESULTS: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p=0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p=0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. CONCLUSIONS: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients.

Relating Tuberculosis (TB) Contact Characteristics to QuantiFERON-TB-Gold and Tuberculin Skin Test Results in the Toronto Pediatric TB Clinic.

BACKGROUND: Few data relate interferon-γ-release-assay results in children to source case sputum status, the best predictor of infectiousness of tuberculosis (TB) patients. We evaluated the QuantiFERON-Gold-in-tube assay (QFT) and tuberculin skin test (TST) in children with different types of TB exposure. METHODS: The TST and QFT were performed in referred TB-exposed children and adolescents who had not undergone prior TST screening (tested in parallel), and the QFT was performed in referred TST-positive individuals. Source case characteristics were obtained from referring public health units. We excluded children with known immunocompromising conditions and those known to have TB disease at the time of evaluation. RESULTS: For 103 patients tested in parallel, overall test agreement was very good in the Bacillus Calmette-Guerein (BCG) unimmunized contacts (κ = 0.83) and contacts of household smear-positive (HS+) cases (κ = 0.67), but test agreement was poor in those with lower-risk contact (κ = 0.34). Only 3 of 59 HS+ patients were QFT-positive and TST-negative. On multivariate analysis, a positive QFT was strongly associated with HS+ exposure (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.2-20]) but not BCG; and a positive TST was associated with BCG alone. For 92 referred TST-positive individuals, the QFT was negative in 21% of HS+ contacts, 65% of lower-risk contacts (OR, 6.8; 95% CI, 1.9-25), and 82% of the patients with unknown contact history (OR, 15.5; 95% CI, 5-54). Application of the Canadian 2010 guidelines would exclude from treatment 43 (72%) of the 73 TST+, QFT- patients. CONCLUSIONS: For close contacts of HS+ individuals, the QFT added little sensitivity to the TST for detection of TB infection. The QFT correlated much better with exposure than the TST, especially in BCG-immunized children, and it has the greatest potential benefit for evaluation of those at lower risk of latent TB infection.

Quantiferon Gold-in-tube assay for TB screening in HIV infected children: influence of quantitative values.

BACKGROUND: HIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children. METHODS: HIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed. RESULTS: Eighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up. CONCLUSIONS: QFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult.

Early initiation of combination antiretroviral therapy in HIV-1-infected newborns can achieve sustained virologic suppression with low frequency of CD4+ T cells carrying HIV in peripheral blood.

BACKGROUND: A human immunodeficiency virus type 1 (HIV-1)-infected infant started on combination antiretroviral therapy (cART) at 30 hours of life was recently reported to have no detectable plasma viremia after discontinuing cART. The current study investigated the impact of early cART initiation on measures of HIV-1 reservoir size in HIV-1-infected children with sustained virologic suppression. METHODS: Children born to HIV-1-infected mothers and started on cART within 72 hours of birth at 3 Canadian centers were assessed. HIV serology, HIV-1-specific cell-mediated immune responses, plasma viremia, cell-associated HIV-1 DNA and RNA, presence of replication-competent HIV-1, and HLA genotype were determined for HIV-1-infected children with sustained virologic suppression. RESULTS: Of 136 cART-treated children, 12 were vertically infected (8.8%). In the 4 who achieved sustained virologic suppression, HIV serology, HIV-1-specific cell-mediated immune responses (Gag, Nef), and ultrasensitive viral load were negative. HIV-1 DNA was not detected in enriched CD4(+) T cells of the 4 children (<2.6 copies/10(6) CD4(+) T cells), whereas HIV-1 RNA was detected (19.5-130 copies/1.5 µg RNA). No virion-associated HIV-1 RNA was detected following mitogenic stimulation of peripheral blood CD4(+) T cells (5.4-8.0 million CD4(+) T cells) in these 4 children, but replication competent virus was detected by quantitative co-culture involving a higher number of cells in 1 of 2 children tested (0.1 infectious units/10(6) CD4(+) T cells). CONCLUSIONS: In perinatally HIV-1-infected newborns, initiation of cART within 72 hours of birth may significantly reduce the size of the HIV-1 reservoirs. Cessation of cART may be necessary to determine whether functional HIV cure can be achieved in such children.

The MaBwana Black men's study: community and belonging in the lives of African, Caribbean and other Black gay men in Toronto.

In Canada, there is a paucity of research aimed at understanding Black gay men and the antecedents to risk factors for HIV. This study is an attempt to move beyond risk factor analysis and explore the role of sexual and ethnic communities in the lives of these men. The study utilized a community-based research and critical race theory approach. Semi-structured interviews were conducted with eight key informants to augment our understanding of Black gay men and to facilitate recruitment of participants. In-depth interviews were done with 24 Black gay men. Our data showed that the construction of community for Black gay men is challenged by their social and cultural environment. However, these men use their resilience to navigate gay social networks. Black gay men expressed a sense of abjuration from both gay and Black communities because of homophobia and racism. It is essential for health and social programmers to understand how Black gay men interact with Black and gay communities and the complexities of their interactions in creating outreach educational, preventive and support services.

A national review of vertical HIV transmission.

OBJECTIVES: Prevention of vertical HIV transmission has evolved significantly in Canada over the last two decades. The aim of this analysis is to describe the surveillance programme used, rate of vertical HIV transmission and changing epidemiology of HIV-affected pregnancies in Canada. DESIGN: National perinatal HIV surveillance programme. METHODS: From 1990, annual retrospective data was collected on demographic and clinical characteristics of HIV-infected mothers and their infants referred to 22 participating sites across Canada either before/during pregnancy or within 3 months after delivery. Factors impacting HIV transmission and demographic features were explored. RESULTS: Two thousand, six hundred and ninety-two mother-infant pairs were identified. The overall rate of vertical HIV transmission was 5.2%, declining to 2.9% since 1997. The rate of transmission for mothers who received HAART was 1%, and 0.4% if more than 4 weeks of HAART was given. Forty percent of women delivered by caesarean section, with no difference in transmission rate compared with vaginal delivery for women treated with HAART (1.4 vs. 0.6%, P = 0.129) but significant risk reduction for those who did not receive HAART (3.8 vs. 10.3%, P = 0.016). Black women were the largest group; proportions of black and aboriginal women increased significantly over time (P < 0.001 for both). Heterosexual contact was the most common risk category for maternal infection (65%), followed by injection drug use (IDU) (25%). CONCLUSION: Vertical HIV transmission in Canada has decreased dramatically for women treated with HAART therapy. All pregnant women should be evaluated for HIV infection and programmes expanded to reach vulnerable populations including aboriginal, immigrant and IDU women.

Vitamin D supplementation and CD4 count in children infected with human immunodeficiency virus.

OBJECTIVE: To evaluate, in a randomized fashion, the impact of vitamin D supplementation on CD4 count and measures of vitamin D homeostasis in children infected with human immunodeficiency virus (HIV). STUDY DESIGN: Children infected with HIV (n = 54) were randomized to receive no supplementation (group 1), vitamin D 5600 IU/week (group 2), or vitamin D 11 200 IU/week (group 3) for 6 months. Viral load, CD4 percent, CD4 count, 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D, and other measures of vitamin D metabolism were measured at baseline and 6 months later. RESULTS: A total of 53 participants completed the study. The mean age, CD4 percent, CD4 count, and log(10) viral load at baseline were 10.3 ± 3.9 years, 33% ± 10%, 927 ± 468 cells/µL, and 1.63 (95% CI, 0.76-2.50), respectively. The mean baseline 25(OH)D level was 53.1 ± 24.8 nmol/L; 85% of participants were vitamin D insufficient or deficient (<75 nmol/L). Serum levels of 25(OH)D increased significantly in participants who received supplementation with vitamin D (P = .0002 and P < .001 for participants receiving 800 IU/day and 1600 IU/day, respectively), but not in participants who did not receive supplementation (P = .27). Participants treated with 1600 IU/day of vitamin D achieved a higher mean increase in 25(OH)D than participants treated with 800 IU/day (P = .02). However, only 67% of the group supplemented with higher dose achieved vitamin D sufficiency. Vitamin D supplementation did not lead to an increase in CD4 percent or CD4 count. CONCLUSION: In children infected with HIV with relatively preserved immune function, vitamin D supplementation in doses as high as 1600 IU/day does not impact CD4 count. Vitamin D insufficiency is common in this population, and achieving vitamin D serum levels of >75 nmol/L may require a daily intake ≥1600 IU.