BackgroundImprovements in life expectancy and quality of life for HIV-positive women coupled with reduced vertical transmission will likely lead numerous HIV-positive women to consider becoming pregnant. In order to clarify the demand, and aid with appropriate health services planning for this population, our study aims to assess the fertility desires and intentions of HIV-positive women of reproductive age living in Ontario, Canada.Methodology/Principal FindingsA cross-sectional study with recruitment stratified to match the geographic distribution of HIV-positive women of reproductive age (18–52) living in Ontario was carried out. Women were recruited from 38 sites between October 2007 and April 2009 and invited to complete a 189-item self-administered survey entitled “The HIV Pregnancy Planning Questionnaire” designed to assess fertility desires, intentions and actions. Logistic regression models were fit to calculate unadjusted and adjusted odds ratios of significant predictors of fertility intentions. The median age of the 490 participating HIV-positive women was 38 (IQR, 32–43) and 61%, 52%, 47% and 74% were born outside of Canada, living in Toronto, of African ethnicity and currently on antiretroviral therapy, respectively. Of total respondents, 69% (95% CI, 64%–73%) desired to give birth and 57% (95% CI, 53%–62%) intended to give birth in the future. In the multivariable model, the significant predictors of fertility intentions were: younger age (age<40) (p<0.0001), African ethnicity (p<0.0001), living in Toronto (p = 0.002), and a lower number of lifetime births (p = 0.02).Conclusions/SignificanceThe proportions of HIV-positive women of reproductive age living in Ontario desiring and intending pregnancy were higher than reported in earlier North American studies. Proportions were more similar to those reported from African populations. Healthcare providers and policy makers need to consider increasing services and support for pregnancy planning for HIV-positive women. This may be particularly significant in jurisdictions with high levels of African immigration.

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).

Despite advances in HIV treatment and care, the current care landscape is inadequate to meet women's comprehensive care needs. A women-centered approach to HIV care, as envisioned by women living with HIV, is central to guiding policy and practice to improve care and outcomes for women living with HIV in Canada.

The clinical pharmacokinetics of metronidazole following oral, intravenous, rectal, and intravaginal doses are described. Peak serum concentrations are quite similar after oral or intravenous administration and average approximately 10 pg/ml after a single 500mg dose. After an oral dose the peak serum concentration is reached approximately 1 hour after administration. Food does not significantly affect absorption, and the bioavailability of the dose approaches 100%. For both intravenous and oral administration, a linear doseconcentration curve pertained for usual therapeutic doses between 200 and 2000mg.Multiple oral or intravenous doses given every 6 to 8 hours result in some drug accumulation with higher serum concentrations as compared with single doses. On an intravenous dose regimen of 500mg every 8 hours, maximum metronidazole serum concentrations average 25 p.glml and minimum concentrations 15 p.g/ml. Rectal administration of metronidazole by suppository resulted in peak serum concentrations approximately one-half those following equivalent oral doses and occurred at 4 hours after administration; the bioavailability of the rectal suppository was approximately 80%. From the limited data available, the systemic absorption of intravaginal metronidazole is very slow with peak serum concentrations of approximately 2 p.g/ml being attained 8 to 24 hours after administration of a 500mg dose.Metronidazole is excreted in the urine as unchanged drug and primarily oxidative metabolites, the major compounds being the hydroxy and acid metabolites. The degree of urinary excretion is dependent upon the assay used. By bioassay, 15 to 20% of the administered dose is excreted as bioactive drug. By high pressure liquid chromatography, in which unchanged metronidazole and the hydroxy and acid metabolites are measured separately, total excretion of these compounds after 48 hours is approximately 30%, with the hydroxy metabolite being the primary excretory product. Detailed pharmacokinetic analysiS of metronidazole has been performed using I-compartment and 2-compartment open models. The serum half-life of unchanged metronidazole averaged 8.2 hours, as determined by specific chemical methods, whereas using bioassay methods the half-life was somewhat longer. A 2-compartment open model analysis described the serum concentration-time curve with a rapid a (distribution) phase (half-life 1.24 hours)and a slower /3 (elimination) phase (half-life 9.76 hours). Metronidazole has a large apparent volume of distribution and serum protein binding of 20% or less. In multiple-dose regimens the hydroxy metabolite of metronidazole may be present in concentrations up to 30% of those of the parent drug with a half-life of 9. 7 hours. The acid metabolite is rarely detected in serum. Metronidazole is widely distributed throughout the body with tissue levels, in most cases, approximating serum levels. This is especially important in the central nervous system where the drug readily crosses both the blood-brain and blood-cerebrospinal flUid barriers....

Background:Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada.Methods:We used baseline survey data from a national cohort of women living with HIV in Canada (n = 1425). Structural equation modeling using weighted least squares estimation methods was conducted to test the direct effects of HIV-related stigma dimensions (personalized, negative self-image, and public attitudes) on ART initiation, current ART use, and 90% ART adherence, and indirect effects through depression and HIV disclosure concerns, adjusting for sociodemographic factors.Results:In the final model, the direct paths from personalized stigma to ART initiation (β = −0.104, P < 0.05) and current ART use (β = −0.142, P < 0.01), and negative self-image to ART initiation (β = −0.113, P < 0.01) were significant, accounting for the mediation effects of depression and HIV disclosure concerns. Depression mediated the pathways from personalized stigma to ART adherence, and negative self-image to current ART use and ART adherence. Final model fit indices suggest that the model fit the data well [χ2(25) = 90.251, P < 0.001; comparative fit index = 0.945; root-mean-square error of approximation = 0.044].Conclusions:HIV-related stigma is associated with reduced likelihood of ART initiation and current ART use, and suboptimal ART adherence. To optimize the benefit of ART among women living with HIV, interventions should reduce HIV-related stigma and address depression.