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1.  Association between Childhood Physical Abuse, Unprotected Receptive Anal Intercourse and HIV Infection among Young Men Who Have Sex with Men in Vancouver, Canada 
PLoS ONE  2014;9(6):e100501.
Introduction
The association between childhood sexual abuse and HIV risk among men who have sex with men (MSM) is well established. However, no studies have examined the potential impact of other forms of childhood maltreatment on HIV incidence in this population.
Methods
We explored the impact of child physical abuse (CPA) on HIV seroconversion in a cohort of gay/bisexual men aged 15 to 30 in Vancouver, Canada. Cox proportional hazard models were used, controlling for confounders.
Results
Among 287 participants, 211 (73.5%) reported experiencing CPA before the age of 17, and 42 (14.6%) reporting URAI in the past year. After a median of 6.6 years follow-up, 16 (5.8%) participants HIV-seroconverted. In multivariate analysis, CPA was significantly associated with HIV seroconversion (adjusted hazard ratio [AHR] = 4.89, 95% confidence interval (CI): 1.65–14.48), after controlling for potential confounders.
Conclusion
Our study uncovered a link between childhood physical violence and HIV incidence. Results highlight an urgent need for screening of young gay and bisexual men for histories of violence, and social and structural supports to prevent HIV transmission in this population.
doi:10.1371/journal.pone.0100501
PMCID: PMC4070929  PMID: 24963804
2.  The cascade of HIV care in British Columbia, Canada, 1996–2011: a population-based retrospective cohort study 
The Lancet infectious diseases  2013;14(1):40-49.
Summary
Background
The cascade of HIV care has become a focal point for implementation efforts to maximise the individual and public health benefits of antiretroviral therapy. We aimed to characterise longitudinal changes in engagement with the cascade of HIV care in British Columbia, Canada, from 1996 to 2011.
Methods
We used estimates of provincial HIV prevalence from the Public Health Agency of Canada and linked provincial population-level data to define, longitudinally, the numbers of individuals in each of the eight stages of the cascade of HIV care (HIV infected, diagnosed, linked to HIV care, retained in HIV care, highly active antiretroviral therapy (HAART) indicated, on HAART, adherent to HAART, and virologically suppressed) in British Columbia from 1996 to 2011. We used sensitivity analyses to determine the sensitivity of cascade-stage counts to variations in their definitions.
Findings
13 140 people were classified as diagnosed with HIV/AIDS in British Columbia during the study period. We noted substantial improvements over time in the proportions of individuals at each stage of the cascade of care. Based on prevalence estimates, the proportion of unidentified HIV-positive individuals decreased from 49·0% (estimated range 36·2–57·5%) in 1996 to 29·0% (11·6–40·7%) in 2011, and the proportion of HIV-positive people with viral suppression reached 34·6% (29·0–43·1%) in 2011.
Interpretation
Careful mapping of the cascade of care is crucial to understanding what further efforts are needed to maximise the beneficial effects of available interventions and so inform efforts to contain the spread of HIV/AIDS.
Funding
British Columbia Ministry of Health, US National Institute on Drug Abuse (National Institutes of Health).
doi:10.1016/S1473-3099(13)70254-8
PMCID: PMC4017913  PMID: 24076277
3.  Trends and Disparities in Antiretroviral Therapy Initiation and Virologic Suppression Among Newly Treatment-Eligible HIV-Infected Individuals in North America, 2001–2009 
Hanna, David B. | Buchacz, Kate | Gebo, Kelly A. | Hessol, Nancy A. | Horberg, Michael A. | Jacobson, Lisa P. | Kirk, Gregory D. | Kitahata, Mari M. | Korthuis, P. Todd | Moore, Richard D. | Napravnik, Sonia | Patel, Pragna | Silverberg, Michael J. | Sterling, Timothy R. | Willig, James H. | Lau, Bryan | Althoff, Keri N. | Crane, Heidi M. | Collier, Ann C. | Samji, Hasina | Thorne, Jennifer E. | Gill, M. John | Klein, Marina B. | Martin, Jeffrey N. | Rodriguez, Benigno | Rourke, Sean B. | Gange, Stephen J. | Benson, A. | Bosch, Ronald J. | Collier, Ann C. | Boswell, Stephen | Grasso, Chris | Mayer, Ken | Hogg, Robert S. | Harrigan, Richard | Montaner, Julio | Cescon, Angela | Brooks, John T. | Buchacz, Kate | Gebo, Kelly A. | Moore, Richard D. | Rodriguez, Benigno | Horberg, Michael A. | Silverberg, Michael J. | Thorne, Jennifer E. | Goedert, James J. | Jacobson, Lisa P. | Klein, Marina B. | Rourke, Sean B. | Burchell, Ann | Rachlis, Anita R. | Hunter-Mellado, Robert F. | Mayor, Angel M. | Gill, M. John | Deeks, Steven G. | Martin, Jeffrey N. | Saag, Michael S. | Mugavero, Michael J. | Willig, James | Eron, Joseph J. | Napravnik, Sonia | Kitahata, Mari M. | Crane, Heidi M. | Justice, Amy C. | Dubrow, Robert | Fiellin, David | Sterling, Timothy R. | Haas, David | Bebawy, Sally | Turner, Megan | Gange, Stephen J. | Anastos, Kathryn | Moore, Richard D. | Saag, Michael S. | Gange, Stephen J. | Kitahata, Mari M. | McKaig, Rosemary G. | Justice, Amy C. | Freeman, Aimee M. | Moore, Richard D. | Freeman, Aimee M. | Lent, Carol | Platt, Aaron | Kitahata, Mari M. | Van Rompaey, Stephen E. | Crane, Heidi M. | Webster, Eric | Morton, Liz | Simon, Brenda | Gange, Stephen J. | Abraham, Alison G. | Lau, Bryan | Althoff, Keri N. | Zhang, Jinbing | Jing, Jerry | Golub, Elizabeth | Modur, Shari | Hanna, David B. | Rebeiro, Peter | Wong, Cherise | Mendes, Adell
In the last decade, timely initiation of antiretroviral therapy and resulting virologic suppression have greatly improved in North America concurrent with the development of better tolerated and more potent regimens, but significant barriers to treatment uptake remain.
Background. Since the mid-1990s, effective antiretroviral therapy (ART) regimens have improved in potency, tolerability, ease of use, and class diversity. We sought to examine trends in treatment initiation and resulting human immunodeficiency virus (HIV) virologic suppression in North America between 2001 and 2009, and demographic and geographic disparities in these outcomes.
Methods. We analyzed data on HIV-infected individuals newly clinically eligible for ART (ie, first reported CD4+ count <350 cells/µL or AIDS-defining illness, based on treatment guidelines during the study period) from 17 North American AIDS Cohort Collaboration on Research and Design cohorts. Outcomes included timely ART initiation (within 6 months of eligibility) and virologic suppression (≤500 copies/mL, within 1 year). We examined time trends and considered differences by geographic location, age, sex, transmission risk, race/ethnicity, CD4+ count, and viral load, and documented psychosocial barriers to ART initiation, including non–injection drug abuse, alcohol abuse, and mental illness.
Results. Among 10 692 HIV-infected individuals, the cumulative incidence of 6-month ART initiation increased from 51% in 2001 to 72% in 2009 (Ptrend < .001). The cumulative incidence of 1-year virologic suppression increased from 55% to 81%, and among ART initiators, from 84% to 93% (both Ptrend < .001). A greater number of psychosocial barriers were associated with decreased ART initiation, but not virologic suppression once ART was initiated. We found significant heterogeneity by state or province of residence (P < .001).
Conclusions. In the last decade, timely ART initiation and virologic suppression have greatly improved in North America concurrent with the development of better-tolerated and more potent regimens, but significant barriers to treatment uptake remain, both at the individual level and systemwide.
doi:10.1093/cid/cit003
PMCID: PMC3657490  PMID: 23315317
antiretroviral therapy; healthcare disparities; HIV; time factors; viral load
4.  Invasive cervical cancer risk among HIV-infected women: A North American multi-cohort collaboration prospective study 
Objective
HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.
Methods
Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction.
Results
A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥ 350, 200–349 and <200 cells/uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (Ptrend =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results.
Conclusions
This study found elevated incidence of ICC in HIV-infected compared to -uninfected women, and these rates increased with immunosuppression.
doi:10.1097/QAI.0b013e31828177d7
PMCID: PMC3633634  PMID: 23254153
Human papilloma virus; HIV-infection; Invasive Cervical Cancer; Immunosuppression
5.  Gender Inequities in Quality of Care among HIV-Positive Individuals Initiating Antiretroviral Treatment in British Columbia, Canada (2000–2010) 
PLoS ONE  2014;9(3):e92334.
Objectives
We measured gender differences in “Quality of Care” (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women.
Design
QOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (≥19 years) who initiated ART in British Columbia, Canada (2000–2010).
Methods
PCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0–6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women.
Results
QOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC = 1.54 (SD = 1.30)) compared with women (mean = 1.89 (SD = 1.37); p<0.001). In the multivariable model, female gender (AOR = 1.16 [95% CI: 0.99–1.35]; p = 0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC.
Conclusions
Poorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV.
doi:10.1371/journal.pone.0092334
PMCID: PMC3958538  PMID: 24642949
6.  Retention Among North American HIV–infected Persons in Clinical Care, 2000–2008 
Background
Retention in care is key to improving HIV outcomes. Our goal was to describe “churn” in patterns of entry, exit, and retention in HIV care in the US and Canada.
Methods
Adults contributing ≥1 CD4 count or HIV-1 RNA (HIV-lab) from 2000–2008 in North American Cohort Collaboration on Research and Design (NA-ACCORD) clinical cohorts were included. Incomplete retention was defined as lack of 2 HIV-labs (≥90 days apart) within 12 months, summarized by calendar year. We used beta-binomial regression models to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) of factors associated with incomplete retention.
Results
Among 61,438 participants, 15,360 (25%) with incomplete retention significantly differed in univariate analyses (p<0.001) from 46,078 (75%) consistently retained by age, race/ethnicity, HIV risk, CD4, ART use, and country of care (US vs. Canada). From 2000–2004, females (OR=0.82, CI:0.70–0.95), older individuals (OR=0.78, CI:0.74–0.83 per 10 years), and ART users (OR= 0.61, CI:0.54–0.68 vs all others) were less likely to have incomplete retention, while black individuals (OR=1.31, CI:1.16–1.49, vs. white), those with injection drug use (IDU) HIV risk (OR=1.68, CI:1.49–1.89, vs. non-IDU) and those in care longer (OR=1.09, CI:1.07–1.11 per year) were more likely to have incomplete retention. Results from 2005–2008 were similar.
Discussion
From 2000 to 2008, 75% of the NA-ACCORD population was consistently retained in care with 25% experiencing some change in status, or churn. In addition to the programmatic and policy implications, our findings identify patient groups who may benefit from focused retention efforts.
doi:10.1097/QAI.0b013e31827f578a
PMCID: PMC3661708  PMID: 23242158
retention; churn; HIV clinical care; North America; HRSA HAB; National HIV/AIDS Strategy
7.  Expansion of HAART Coverage Is Associated with Sustained Decreases in HIV/AIDS Morbidity, Mortality and HIV Transmission: The “HIV Treatment as Prevention” Experience in a Canadian Setting 
PLoS ONE  2014;9(2):e87872.
Background
There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized.
Methods
We used population-level longitudinal data from province-wide registries including plasma viral load, CD4 count, drug resistance, HAART use, HIV diagnoses, AIDS incidence, and HIV-related mortality. We fitted two Poisson regression models over the study period, to relate estimated HIV incidence and the number of individuals on HAART and the percentage of virologically suppressed individuals.
Results
HAART coverage, median pre-HAART CD4 count, and HAART adherence increased over time and were associated with increasing virological suppression and decreasing drug resistance. AIDS incidence decreased from 6.9 to 1.4 per 100,000 population (80% decrease, p = 0.0330) and HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003). Finally, our models suggested that for each increase of 100 individuals on HAART, the estimated HIV incidence decreased 1.2% and for every 1% increase in the number of individuals suppressed on HAART, the estimated HIV incidence also decreased by 1%.
Conclusions
Our results show that HAART expansion between 1996 and 2012 in BC was associated with a sustained and profound population-level decrease in morbidity, mortality and HIV transmission. Our findings support the long-term effectiveness and sustainability of HIV treatment as prevention within an adequately resourced environment with no financial barriers to diagnosis, medical care or antiretroviral drugs. The 2013 Consolidated World Health Organization Antiretroviral Therapy Guidelines offer a unique opportunity to further evaluate TasP in other settings, particularly within generalized epidemics, and resource-limited setting, as advocated by UNAIDS.
doi:10.1371/journal.pone.0087872
PMCID: PMC3922718  PMID: 24533061
8.  Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy 
AIDS care  2012;25(1):10.1080/09540121.2012.687809.
This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy (ART) in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer-administered survey. Clinical variables (i.e. CD4 count) were obtained through linkages with the British Columbia HIV/AIDS Drug Treatment Program. Multivariable linear regression was performed to determine the independent predictors of stigma. Our results indicate that among participants with high school education or greater the outcome stigma, was associated with a 3.05 stigma unit decrease (95% CI: −5.16, −0.93). Having higher relative standard of living and perceiving greater neighborhood cohesion were also associated with a decrease in stigma (−5.30 95% CI: −8.16, −2.44; −0.80 95% CI: −1.39, −0.21, respectively). Lower levels of stigma were found to be associated with better QoL measures, including perceiving better overall function (−0.90 95% CI: −1.47, −0.34), having fewer health worries (−2.11 95% CI: −2.65, −1.57), having fewer financial worries (−0.67 95% CI: −1.12, −0.23), and having less HIV disclosure concerns (−4.12 95% CI: −4.63, −3.62). The results of this study show that participants with higher education level, better QoL measures, and higher self-reported standards of living are less likely to perceive HIV-related stigma.
doi:10.1080/09540121.2012.687809
PMCID: PMC3879041  PMID: 22672228
stigma; ART; quality of life; HIV
9.  Gender Differences in Clinical Outcomes among HIV-Positive Individuals on Antiretroviral Therapy in Canada: A Multisite Cohort Study 
PLoS ONE  2013;8(12):e83649.
Background
Cohort data examining differences by gender in clinical responses to combination antiretroviral therapy (ART) remain inconsistent and have yet to be explored in a multi-province Canadian setting. This study investigates gender differences by injection drug use (IDU) history in virologic responses to ART and mortality.
Methods
Data from the Canadian Observational Cohort (CANOC) collaboration, a multisite cohort study of HIV-positive individuals initiating ART after January 1, 2000, were included. This analysis was restricted to participants with a follow-up HIV-RNA plasma viral load measure and known IDU history. Weibull hazard regression evaluated time to virologic suppression (2 consecutive measures <50 copies/mL), rebound (>1000 copies/mL after suppression), and all-cause mortality. Sensitivity analyses explored the impact of presumed ART use in pregnancy on virologic outcomes.
Results
At baseline, women (1120 of 5442 participants) were younger (median 36 vs. 41 years) and more frequently reported IDU history (43.5% vs. 28.8%) (both p<0.001). Irrespective of IDU history, in adjusted multivariable analyses women were significantly less likely to virologically suppress after ART initiation and were at increased risk of viral load rebound. In adjusted time to death analysis, no differences by gender were noted. After adjusting for presumed ART use in pregnancy, observed gender differences in time to virologic suppression for non-IDU, and time to virologic rebound for IDU, became insignificant.
Conclusions
HIV-positive women in CANOC are at heightened risk for poor clinical outcomes. Further understanding of the intersections between gender and other factors augmenting risk is needed to maximize the benefits of ART.
doi:10.1371/journal.pone.0083649
PMCID: PMC3877405  PMID: 24391803
10.  Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada 
PLoS ONE  2013;8(12):e81355.
Background
Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.
Methods
Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.
Results
The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000–2002 to 2006–2007. Men and women had comparable life expectancies in all periods except the last (2006–2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm3.
Conclusions
A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.
doi:10.1371/journal.pone.0081355
PMCID: PMC3867319  PMID: 24367482
11.  Heterogeneity in outcomes of treated HIV-positive patients in Europe and North America: relation with patient and cohort characteristics 
Background HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear.
Methods We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.
Results During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts’ estimated completeness of death ascertainment [excellent: 96–100%, good: 90–95%, average: 75–89%; mortality rate ratio 0.66 (95% confidence interval 0.46–0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31–0.57) before and 0.47 (0.30–0.73) after adjusting for completeness of ascertainment.
Conclusions Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.
doi:10.1093/ije/dys164
PMCID: PMC3535877  PMID: 23148105
HIV; AIDS; antiretroviral therapy; mortality; cohort; heterogeneity; prognostic model; socio-economic status
12.  Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy 
PLoS ONE  2013;8(10):e77665.
Background
HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death.
Methods
A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000–2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models.
Results
4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm3, baseline CD8+ T-cells <500 cells/mm3, time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death.
Conclusions
In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.
doi:10.1371/journal.pone.0077665
PMCID: PMC3813720  PMID: 24204912
13.  Use of North America’s first medically supervised safer injecting facility among HIV-positive injection drug users 
The objective of this study was to examine supervised injecting facility (SIF) use among a cohort of 395 HIV-positive injection drug users (IDUs) in Vancouver, Canada. The correlates of SIF use were identified using generalized estimating equation analyses. In multivariate analyses, frequent SIF use was associated with homelessness (adjusted odds ratio [AOR] = 1.90), daily heroin injection (AOR = 1.56), and daily cocaine injection (AOR = 1.59). The reasons given for not using the SIF included a preference for injecting at home and already having a safe place to inject. The SIF services most commonly used were needle exchange and nursing services. The SIF appears to have attracted a high-risk subpopulation of HIV-positive IDUs; this coverage perhaps could be extended with the addition of HIV- specific services such as disease monitoring and the provision of antiretroviral therapy.
doi:10.1521/aeap.2011.23.5.412
PMCID: PMC3799861  PMID: 22010805
14.  Risks for HIV and other sexually transmitted infections among Asian men who have sex with men in Vancouver, British Columbia: a cross-sectional survey 
BMC Public Health  2013;13:763.
Background
Individuals of Asian heritage represent the largest ethnic minority in Canada. Approximately 10% of the new HIV diagnoses in men in British Columbia occur among Asian-Canadians. However, the HIV risk patterns of Asian men who have sex with men (MSM) have not been extensively studied.
Methods
Participants aged ≥ 19 years were enrolled in a venue-based HIV serobehavioural survey of MSM in Vancouver, Canada. We compared the demographic characteristics, risk behaviours, and prevalence of HIV and other sexual and blood borne infections between Asian and non-Asian MSM using bivariate analysis and logistic regression confounder modelling.
Results
Amongst 1132 participants, 110 (9.7%) self-identified as Asian. Asian participants were younger than non-Asian participants (median age 29 vs. 32 years; p < 0.001), but otherwise did not differ from other study participants. HIV prevalence was lower among Asian MSM compared to Non-Asian MSM (3.7% vs 19.0%, p <0.001). Among men who self-reported as HIV negative or unknown we found no differences in unprotected anal intercourse (UAI) with a discordant or unknown serostatus partner in the previous six months (11 vs. 13%; p = 0.503). However, Asian MSM were less likely to report ever using injection drugs (10.8% vs. 19.2%; p = 0.043) or using alcohol before having sex (52% vs. 64.4%; p = 0.017).
Conclusions
Asian MSM in our study reported similar rates of UAI as non-Asian MSM, but had a lower prevalence of HIV infection. Other factors, such as the use of drugs and alcohol, in relation to sex, may partly explain these differences. However this requires further investigation.
doi:10.1186/1471-2458-13-763
PMCID: PMC3751745  PMID: 23947623
HIV; Homosexuality; Men who have sex with men; Asian
15.  The association between food insecurity and mortality among HIV-infected individuals on HAART 
Background
Food insecurity is increasingly recognized as a barrier to optimal treatment outcomes but there is little data on this issue. We assessed associations between food insecurity and mortality in HIV-infected antiretroviral therapy (ART)-treated individuals in Vancouver, British Columbia (BC), and whether body max index (BMI) modified associations.
Methods
Individuals were recruited from the BC HIV/AIDS drug treatment program in 1998 and 1999, and were followed until June 2007 for outcomes. Food insecurity was measured with the Radimer/Cornell questionnaire. Cox proportional hazard models were used to determine associations between food insecurity, BMI and non-accidental deaths when controlling for confounders.
Results
Among 1119 participants, 536 (48%) were categorized as food insecure and 160 (14%) were categorized as underweight (BMI <18.5). After a median follow-up time of 8.2 years, 153 individuals (14%) had died from non-accidental deaths. After controlling for adherence, CD4 counts, and socioeconomic variables, people who were food insecure and underweight were nearly two times more likely to die (Adjusted hazard ratio [AHR]=1.94, 95% Confidence interval [CI]=1.10-3.40) compared with people who were not food insecure or underweight. There was also a trend towards increased risk of mortality among people who were food insecure and not underweight (AHR= 1.40, 95% CI=0.91-2.05). In contrast, people who were underweight but food secure were not more likely to die.
Conclusions
Food insecurity is a risk factor for mortality among ART-treated individuals in BC, particularly among individuals who are underweight. Innovative approaches to address food insecurity should be incorporated into HIV treatment programs.
doi:10.1097/QAI.0b013e3181b627c2
PMCID: PMC3740738  PMID: 19675463
Food insecurity; HIV/AIDS; mortality; Vancouver
16.  Relationship between Food Insecurity and Mortality among HIV-Positive Injection Drug Users Receiving Antiretroviral Therapy in British Columbia, Canada 
PLoS ONE  2013;8(5):e61277.
Objectives
Little is known about the potential impact of food insecurity on mortality among people living with HIV/AIDS. We examined the potential relationship between food insecurity and all-cause mortality among HIV-positive injection drug users (IDU) initiating antiretroviral therapy (ART) across British Columbia (BC).
Methods
Cross-sectional measurement of food security status was taken at participant ART initiation. Participants were prospectively followed from June 1998 to September 2011 within the fully subsidized ART program. Cox proportional hazard models were used to ascertain the association between food insecurity and mortality, controlling for potential confounders.
Results
Among 254 IDU, 181 (71.3%) were food insecure and 108 (42.5%) were hungry. After 13.3 years of median follow-up, 105 (41.3%) participants died. In multivariate analyses, food insecurity remained significantly associated with mortality (adjusted hazard ratio [AHR] = 1.95, 95% CI: 1.07–3.53), after adjusting for potential confounders.
Conclusions
HIV-positive IDU reporting food insecurity were almost twice as likely to die, compared to food secure IDU. Further research is required to understand how and why food insecurity is associated with excess mortality in this population. Public health organizations should evaluate the possible role of food supplementation and socio-structural supports for IDU within harm reduction and HIV treatment programs.
doi:10.1371/journal.pone.0061277
PMCID: PMC3664561  PMID: 23723968
17.  Incidence and Predictors of Pregnancy among a Cohort of HIV-Positive Women Initiating Antiretroviral Therapy in Mbarara, Uganda 
PLoS ONE  2013;8(5):e63411.
Objective
Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV prevention strategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexual partners and future children requires a comprehensive understanding of pregnancy in this population. We analyzed prospective cohort data to determine pregnancy incidence and predictors among HIV-positive women initiating antiretroviral therapy (ART) in a setting with high HIV prevalence and fertility.
Methods
Participants were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort of HIV-positive individuals initiating ART in Mbarara. Bloodwork (including CD4 cells/mm3, HIV viral load) and questionnaires (including socio-demographics, health status, sexual behavior, partner dynamics, HIV history, and self-reported pregnancy) were completed at baseline and quarterly. Our analysis includes 351 HIV-positive women (18–49 years) who enrolled between 2005–2011. We measured pregnancy incidence by proximal and distal time relative to ART initiation and used multivariable Cox proportional hazards regression analysis (with repeated events) to identify baseline and time-dependent predictors of pregnancy post-ART initiation.
Results
At baseline (pre-ART initiation), median age was 33 years [IQR: 27–37] and median prior livebirths was four [IQR: 2–6]. 38% were married with 61% reporting HIV-positive spouses. 73% of women had disclosed HIV status to a primary sexual partner. Median baseline CD4 was 137 cells/mm3 [IQR: 81–207]. At enrolment, 9.1% (31/342) reported current pregnancy. After ART initiation, 84 women experienced 105 pregnancies over 3.8 median years of follow-up, yielding a pregnancy incidence of 9.40 per 100 WYs. Three years post-ART initiation, cumulative probability of at least one pregnancy was 28% and independently associated with younger age (Adjusted Hazard Ratio (AHR): 0.89/year increase; 95%CI: 0.86–0.92) and HIV serostatus disclosure to primary sexual partner (AHR: 2.45; 95%CI: 1.29–4.63).
Conclusions
Nearly one-third of women became pregnant within three years of initiating ART, highlighting the need for integrated services to prevent unintended pregnancies and reduce periconception-related risks for HIV-infected women choosing to conceive. Association with younger age and disclosure suggests a role for early and couples-based safer conception counselling.
doi:10.1371/journal.pone.0063411
PMCID: PMC3660357  PMID: 23704906
18.  Young Age Predicts Poor Antiretroviral Adherence and Viral Load Suppression Among Injection Drug Users 
AIDS Patient Care and STDs  2012;26(5):274-280.
Abstract
Previous studies of adherence to antiretroviral therapy (ART) for HIV among young injection drug users (IDU) have been limited because financial barriers to care disproportionately affect youth, thus confounding results. This study examines adherence among IDU in a unique setting where all medical care is provided free-of-charge. From May 1996 to April 2008, we followed a prospective cohort of 545 HIV-positive IDU of 18 years of age or older in Vancouver, Canada. Using generalized estimating equations (GEE), we studied the association between age and adherence (obtaining ART≥95% of the prescribed time), controlling for potential confounders. Using Cox proportional hazards regression, we also studied the effect of age on time to viral load suppression (<500 copies per milliliter), and examined adherence as a mediating variable. Five hundred forty-five participants were followed for a median of 23.8 months (interquartile range [IQR]=8.5–91.6 months). Odds of adherence were significantly lower among younger IDU (adjusted odds ratio [AOR]=0.76 per 10 years younger; 95% confidence interval [CI], 0.65–0.89). Younger IDU were also less likely to achieve viral load suppression (adjusted hazard ratio [AHR]=0.75 per 10 years younger; 95% CI, 0.64–0.88). Adding adherence to the model eliminated this association with age, supporting the role of adherence as a mediating variable. Despite absence of financial barriers, younger IDU remain less likely to adhere to ART, resulting in inferior viral load suppression. Interventions should carefully address the unique needs of young HIV-positive IDU.
doi:10.1089/apc.2011.0196
PMCID: PMC3366333  PMID: 22429003
19.  Social and environmental predictors of plasma HIV RNA rebound among injection drug users treated with antiretroviral therapy 
Introduction
Evidence is needed to improve HIV treatment outcomes for individuals who use injection drugs (IDU). Although studies have suggested higher rates of plasma viral load (PVL) rebound among IDU on antiretroviral therapy (ART), risk factors for rebound have not been thoroughly investigated.
Methods
We used data from a long-running community-recruited prospective cohort of IDU in Vancouver, Canada, linked to comprehensive ART and clinical monitoring records. Using proportional hazards methods, we modeled the time to confirmed PVL rebound above 1000 copies/mL among IDU on ART with sustained viral suppression, defined as two consecutive undetectable PVL measures.
Results
Between 1996 and 2009, 277 individuals had sustained viral suppression. Over a median follow-up of 32 months, 125 participants (45.1%) experienced at least one episode of virologic failure for an incidence of 12.6 (95% Confidence Interval [CI]: 10.5 – 15.0) per 100 person years. In a multivariate model, PVL rebound was independently associated with sex trade involvement (Adjusted Hazard Ratio [AHR] = 1.40, 95% CI: 1.08 – 1.82) and recent incarceration (AHR = 1.83, 95% CI: 1.33 – 2.52). Methadone maintenance therapy (AHR = 0.79, 95% CI: 0.66 – 0.94) was protective. No measure of illicit drug use was predictive.
Conclusions
In this setting of free ART, several social and environmental factors predicted higher risks of viral rebound among IDU, including sex trade involvement and incarceration. These findings should help inform efforts to identify individuals at risk of viral rebound as well as targeted interventions to treat and retain individuals in effective ART.
doi:10.1097/QAI.0b013e3182433288
PMCID: PMC3299888  PMID: 22134149
human immunodeficiency virus (HIV) infection; antiretroviral therapy (ART); injection drug user (IDU); plasma HIV-1 RNA viral load; viral suppression; viral rebound
20.  The Combined Effect of Modern Highly Active Antiretroviral Therapy Regimens and Adherence on Mortality Over Time 
Objective
To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens.
Methods
Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective.
Results
The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value < 0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)–based and boosted protease inhibitor–based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality.
Conclusions
Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.
doi:10.1097/QAI.0b013e31819675e9
PMCID: PMC3606956  PMID: 19223785
adherence; boosted PI; HAART; marginal structural models; mortality; NNRTI
21.  The WHOMEN’s Scale (Women’s HAART Optimism Monitoring and EvaluatioN Scale v.1) and the Association with Fertility Intentions and Sexual Behaviours Among HIV-Positive Women in Uganda 
AIDS and behavior  2009;13(Suppl 1):72-81.
The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale’s validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18–50 years) attending Mbarara University’s HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (α = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12–16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8–12]; P <0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women’s HAART Optimism Monitoring and EvaluatioN scale (WHOMEN’s scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.
doi:10.1007/s10461-009-9553-y
PMCID: PMC3606958  PMID: 19387819
HIV; HAART; Uganda; Scale; HAART optimism; Women; Fertility intentions; Sexual behaviour; HAART optimism scale
22.  Antiretroviral Therapy is Associated with Increased Fertility Desire, but not Pregnancy or Live Birth, among HIV+ Women in an Early HIV Treatment Program in Rural Uganda 
AIDS and behavior  2008;13(Suppl 1):28-37.
To assess the association between antiretroviral therapy (ART) and fertility history and desire among HIV-positive Ugandan women, we conducted a cross-sectional study among HIV-positive Ugandan women aged 18–50 years who attended an HIV clinic at Mbarara University in western Uganda between November 1, 2005 and June 6, 2006. Of 538 women approached, 501 were enrolled. ART use was associated with increased odds of fertility desire (AOR 2.99, 95% CI 1.38–6.28), and decreased odds of pregnancy (AOR 0.56, 95% CI 0.33–0.95) and live birth (AOR 0.30, 95% CI 0.13–0.66). ART was associated with an increase in fertility desire, but was not associated with an increase in fertility. Additional studies will be needed to determine if this greater fertility desire among ART-treated women leads to an increase in fertility as ART use expands.
doi:10.1007/s10461-008-9371-7
PMCID: PMC3606959  PMID: 18389364
Uganda; Fertility; HIV/AIDS; Fertility desires; Antiretroviral therapy
23.  The Relationship Between Resistance and Adherence in Drug-Naive Individuals Initiating HAART Is Specific to Individual Drug Classes 
Objective
To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada.
Methods
Plasma samples with plasma viral load >1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables.
Results
The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%–90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0, 95% CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95% refills with consistently detectable drug levels. Adherence–resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs.
Conclusion
The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.
doi:10.1097/QAI.0b013e318189a753
PMCID: PMC3606960  PMID: 18845950
adherence; HAART; HIV-1 drug resistance; mutations
25.  Application and Validation of Case-Finding Algorithms for Identifying Individuals with Human Immunodeficiency Virus from Administrative Data in British Columbia, Canada 
PLoS ONE  2013;8(1):e54416.
Objective
To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm.
Methods
Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases.
Results
A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p<0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p<0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p<0.01; days of inpatient care: 29/100PY vs. 98/100PY; p<0.01; physician billings: 602/100PY vs. 2,056/100PY; p<0.01).
Conclusions
The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases.
doi:10.1371/journal.pone.0054416
PMCID: PMC3557280  PMID: 23382898

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