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Biomedical subjects

M V O'Shaughnessy

Publications and source records attributed to M V O'Shaughnessy.

At least 19 recordsLinked to original sources
PubMed2005

Quality of life, depression and fatigue among persons co-infected with HIV and hepatitis C: outcomes from a population-based cohort.

The objective of the study was to describe the additional burden generated by hepatitis C (HCV) infection among HIV-infected individuals as measured by self-reported quality of life, depression and fatigue. The provincial HIV/AIDS Drug Treatment Program (DTP) distributes all antiretroviral medication in the province of British Columbia. Eligibility for accessing antiretrovirals is based on published guidelines commensurate with the International AIDS Society. Each participant is asked to complete a self-administered mailed questionnaire that includes patient sociodemographic information, quality of life measures (Medical Outcomes Study-Short Form (MOS-SF), mental health issues (Centre for Epidemiological Studies Depression scale (CESD) and fatigue information. HIV-HCV co-infected individuals were compared to HIV mono-infected individuals using parametric and nonparametric methods. Multivariate logistic regression was used to examine the impact of hepatitis C on quality of life, depression and fatigue, after controlling for sociodemographics and HIV-specific clinical characteristics. Of the 4,134 individuals who were sent a HIV/AIDS DTP survey in 1999, 2000 or 2001, 484 participants both returned one and had an HCV-antibody test result on file. Of the 484 participants eligible for this analysis, 105 (22%) were HCV-positive. In comparison to the 379 (78%) patients testing negative for HCV, a larger proportion of co-infected patients were female (18% versus 3%, p<0.001), aboriginal (20% versus 3%, p<0.001), had ever injected drugs (79% versus 5%, p<0.001), were unemployed (91% versus 49%, p<0.001) and lived in unstable housing (19% versus 1%, p<0.001) at the time they completed the survey. Co-infected patients reported more symptoms consistent with depression, increased fatigue and poorer quality of life. However, using multivariate modeling, it was determined that the impact of HCV on quality of life, depression and fatigue was better explained by the sociodemographic factors related to poverty and injection drug use, than by HCV itself. In conclusion, individuals co-infected with HIV and HCV represent a patient population with significant physical and mental health challenges. Although these patients experience poorer quality of life, increased depression and fatigue, this experience appears to be primarily related to socio-economic issues rather than HCV infection.

AIDS-Related Opportunistic Infections↗
PubMed2003

Surviving the sex trade: a comparison of HIV risk behaviours among street-involved women in two Canadian cities who inject drugs.

In Canada, very little is known about the factors and processes that cause drug-related harm among female intravenous drug users (IDUs). Women who inject drugs and participate in the survival sex trade are considered to be at increased risk for sexual and drug-related harms, including HIV infection. Between September 1999 and September 2000, women participating in the VIDUS cohort in Vancouver and the St. Luc Cohort in Montreal completed interviewer-administered questionnaires. Analyses were conducted to compare the demographic characteristics, sexual risk behaviours, risky injection practices and drug use patterns among women who self-identified as participating in the sex trade with those who did not identify as participating in the sex trade. Logistic regression was used to identify factors independently associated with exchanging sex for money or drugs. HIV prevalence at the study visit (September 1999-2000) was 29% for sex trade workers and 29.2% for non-sex trade workers. While patterns of sexual risk were similar, the risky injection practice and drug use patterns between sex trade workers and non-sex trade workers were markedly different. Logistic regression analysis of cross-sectional data revealed that independent behaviours associated with the sex trade included: greater than once per day use of heroin (adjusted OR 2.7), smokeable crack cocaine (adjusted OR = 3.3) and borrowing used syringes (adjusted OR = 2.0). Creative, client-driven interventions are urgently needed for women who trade sex for money or for drugs.

Adolescent↗
PubMed2003

The impact of needle-exchange programs on the spread of HIV among injection drug users: a simulation study.

OBJECTIVE: To determine the impact of the implementation of a needle-exchange program (NEP) on the spread of human immunodeficiency virus (HIV) in an injection drug user (IDU) community. We conducted a Monte Carlo simulation study of a theoretical population of 10000 IDUs. The population was followed monthly from 1984 to 2000. HIV was assumed to be transmitted only by needle sharing. The NEP was introduced in 1989 and evaluated over a period of 11 years. The impacts of the proportion of the population attending the NEP, the risk level of IDUs attending the NEP, the reduction in needle-sharing frequency, and the number of new needle-sharing partners acquired at the NEP on prevalence and incidence of HIV were determined. Increasing the proportion of the population who always attend the NEP and eliminating needle-sharing incidents among IDUs who always attended the NEP were the most effective ways of reducing the spread of HIV. Attracting high-risk users instead of lower risk users to the NEP also reduced the spread of HIV, but to a lesser extent. NEPs are effective at reducing the spread of HIV; even under the worst case scenario of low risk users more likely to attend the NEP, one additional partner per month as a result of attending the NEP, and poor NEP attendance, the estimated prevalence was still less than that from the scenario without an NEP. Under our model, NEPs were shown to reduce the spread of HIV significantly. Efforts should be focused on getting as many IDUs as possible to become regular NEP attenders and stop sharing needles rather than partially reducing the frequency of sharing by a larger number of IDUs.

British Columbia↗
PubMed2003

Sources and magnitude of intralaboratory variability in a sequence-based genotypic assay for human immunodeficiency virus type 1 drug resistance.

We assessed the intralaboratory reproducibility of a system for sequencing human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) by using replicate subanalyses of 46 plasma samples collected from HIV-1-infected, antiretroviral-experienced patients in order to determine the relative contributions of the different procedural steps to final sequence variability. Complete sequence concordance between duplicates of each sample was 99.4%. Complete and partial mismatches occurred scattered throughout the PR-RT genome segment at >300 positions. Approximately 75% of the discordances involved mixtures, some of which appeared at key resistance sites. Most differences were the result of the first-round RT-PCR procedure. Inter-rater concordance for sequence analysis and assembly was >99.9%. There was no observed correlation between the number or frequency of mismatches and plasma viral loads. A separate longitudinal analysis of a single routine control sample sequenced 103 times over 9 months consistently gave highly reproducible sequences (median percentage of nucleotide discordances, 0.04%; range, 0 to 0.2%). Finally, sequence data from 168 sequential samples collected from 22 patients with long-term, predominantly wild type HIV showed that intrapatient nucleotide concordance with individual index sequences ranged from 96.5 to 100%. Together, these results confirm that sequence-based genotyping can be a precise and reliable tool for monitoring HIV drug resistance, and they suggest that efforts to reduce variability should focus on the first RT-PCR step. Consequently, the data suggest that the composition of external quality assessment panels should be based on clinical HIV isolates rather than DNA clones.

Amino Acid Sequence↗
PubMed2003

Emerging drug toxicities of highly active antiretroviral therapy for human immunodeficiency virus (HIV) infection.

To provide an overview of the epidemiologic parameters of emerging adverse effects associated with antiretroviral therapy for human immunodeficiency virus (HIV) disease. All available antiretroviral agents are associated with significant adverse drug effects. Of particular interest are newly emerging suspected adverse drug effects which were not generally noted in pre-marketing trials nor captured under current standard clinical care practices. Suspected antiretroviral toxicities meeting these criteria include: HIV-associated lipodystrophy which can include peripheral lipoatrophy, lipohypertrophy and metabolic abnormalities; hyperlactatemia and lactic acidosis; and metabolic bone abnormalities such as decreased bone mineral density, osteoporosis and osteonecrosis. Results of prospective and observational studies reported to date suggest that these abnormalities, while aetiologically complex, are likely attributable to treatment factors and may be intricately interrelated. The medical management of these symptoms remains unsatisfactory given the unexplored efficacy of traditional approaches in the HIV positive population. While the pathogenic mechanism of these disorders remains obscure, a theory of tissue-specific mitochondrial toxicity has been proposed. With the continued introduction of novel therapies and standard treatment with combination therapy, new adverse events will continue to emerge among persons being treated for HIV disease. Beyond their immediate clinical implications, these events may contribute to changing patterns of antiretroviral utilisation including therapy initiation, adherence and cessation.

Acidosis, Lactic↗
PubMed2003

High pregnancy rates and reproductive health indicators among female injection-drug users in Vancouver, Canada.

OBJECTIVE: To determine the incidence of pregnancy among active injection-drug users and to identify factors associated with becoming pregnant. METHODS: The Vancouver Injection Drug User Study (VIDUS) is a prospective cohort study that began in 1996. Women who had completed a baseline and at least one follow-up questionnaire between June 1996 and January 2002 were included in the study. Parametric and non-parametric methods were used to compare characteristics of women who reported pregnancy over the study period with those who did not over the same time period. RESULTS: A total of 104 women reported a primary pregnancy over the study period. The incidence of pregnancy over the follow-up period was 6.46 (95% confidence interval (CI) 5.24-7.87) per 100 person-years. The average age of women who reported pregnancy was younger than that of women who did not report pregnancy (27 vs. 32 years, p < 0.001). Women of Aboriginal ethnicity were more likely to report pregnancy (odds ratio 1.6, 95% CI 1.0-2.5). Comparison of drug use showed no significant differences in pregnancy rate with respect to the use of heroin, cocaine or crack (p > 0.05). In examining sexual behavior, women who reported having had a regular partner in the previous 6 months were three times more likely to have reported pregnancy. Despite the fact that 67% of women in this study reported using some form of contraception, the use of reliable birth control was low. Only 5% of women in our study reported the use of hormonal contraceptives. CONCLUSION: There were a high number of pregnancies among high-risk women in this cohort. This corresponded with very low uptake of reliable contraception. Innovative strategies to provide reproductive health services to at-risk women who are injecting drugs is a public health priority.

Adult↗
PubMed2002

Risky sexual behaviours among injection drugs users with high HIV prevalence: implications for STD control.

Injection drug use is inextricably linked to commercial sex work and the transmission of sexually transmitted disease (STD). In many communities prevention efforts have been stalled owing to the marginal existence of this community. This study describes the sexual activities, condom use, reported STDs, and commercial sex work in a large cohort of injection drug users. Seventy two per cent of male and 92% of female subjects in the cohort were sexually active. Among female subjects, 57% reported more than 100 lifetime partners. Condoms were generally not used with regular partners, used about half the time with casual partners, and used about 80% of the time with paying partners. Female sex workers were more likely to have unstable housing and to report incarceration in the previous six months. Reducing the transmission of STDs and HIV in drug using communities is a public health priority. While existing prevention programmes should be strengthened, innovative approaches to STD surveillance, diagnosis, and prevention are needed.

Adolescent↗
PubMed2001

Industry-sponsored clinical research: a double-edged sword.

Drug development has accelerated exponentially since the 1950s. It is difficult to estimate the relative contributions or rates of success of industry sponsored as opposed to government supported research in any field. However, it is clear that much of the therapeutic innovation of recent decades has emerged from biotechnology and pharmaceutical industry sponsored efforts. This sponsorship is leading to new stresses in the relationship between academic institutions and industry.

Academic Medical Centers↗
PubMed2001

Impact of HIV infection on mortality in a cohort of injection drug users.

The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow-up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow-up and detailed causes of death were collected from coroner's reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV-positive participants and 42% among HIV-negative participants. Of the 65 deaths among HIV-positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.

Adolescent↗
PubMed2001

Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy.

CONTEXT: Current recommendations for initiation of antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV) are based on CD4 T-lymphocyte cell counts and plasma HIV RNA levels. The relative prognostic value of each marker following initiation of therapy has not been fully characterized. OBJECTIVE: To describe rates of disease progression to death and AIDS or death among patients starting triple-drug antiretroviral therapy, stratified by baseline CD4 cell count and HIV RNA levels. DESIGN, SETTING, AND PARTICIPANTS: Population-based analysis of 1219 antiretroviral therapy-naive HIV-positive men and women aged 18 years or older in British Columbia who initiated triple-drug therapy between August 1, 1996, and September 30, 1999. MAIN OUTCOME MEASURE: Cumulative mortality rates from the initiation of triple-drug antiretroviral therapy to September 30, 2000, determined using various CD4 cell and plasma HIV RNA thresholds. RESULTS: As of September 30, 2000, 82 patients had died of AIDS-related causes, for a crude AIDS-related mortality rate of 6.7%. The product limit estimate (SE) of the cumulative mortality rate at 12 months was 2.9% (0.5%). In univariate analyses, a prior diagnosis of acquired immunodeficiency syndrome (AIDS), CD4 cell count, use of protease inhibitors, and HIV RNA level were associated with mortality. There was no difference in mortality by age or sex. Only CD4 cell count remained statistically significant in the multivariate analysis. After controlling for AIDS, protease inhibitor use, and plasma HIV RNA level at baseline, patients with CD4 cell counts of less than 50/microL were 6.67 (95% confidence interval [CI], 3.61-12.34) times and those with counts of 50/microL to 199/microL were 3.41 (95% CI, 1.93-6.03) times more likely to die than those with counts of at least 200/microL. CONCLUSION: Our data demonstrate uniformly low rates of disease progression to death and AIDS or death among patients starting antiretroviral therapy with CD4 cell counts of at least 200/microL. In our study, disease progression to death and AIDS or death was clustered among patients starting therapy with CD4 cell counts less than 200/microL.

Adult↗
PubMed2001

CCR5Delta32 and promoter polymorphisms are not correlated with initial virological or immunological treatment response.

OBJECTIVE: Natural genetic polymorphisms within the CCR5 gene and promoter have been linked to patterns of HIV-1 clinical disease progression in untreated individuals. The objective of this retrospective study was to assess the influence of the CCR5Delta32 mutation and promoter polymorphisms on virological and immunological treatment outcome in 436 antiretroviral-naive individuals initiating their first therapy, over a mean follow-up time of 22 months. METHODS: Genotypes for the CCR5Delta32 and promoter were determined by polymerase chain reaction amplification of human DNA from plasma, followed by gel electrophoresis for CCR5Delta32 or DNA sequencing for the promoter polymorphisms. Time to virological failure [defined as the second plasma viral load > or = 400 copies HIV-1 RNA/ml) and immunological failure (defined as time to achieve two successive CD4 cell counts below baseline) were analyzed by Kaplan-Meier methods. RESULTS: The five most common CCR5 promoter polymorphisms were observed at positions 208(G/T), 303(A/G), 627(C/T), 676(A/G), and 927(C/T). Allele frequencies were 0.24(208T), 0.38(303G), 0.44(627T), 0.35(676G) and 0.18(927T). The CCR5Delta32 allele frequency was 0.08. The promoter polymorphisms existed in strong linkage disequilibrium with each other and the Delta32. No significant effect of the individual CCR5Delta32 or promoter polymorphisms could be demonstrated with respect to time to treatment failure as defined by virological or immunological parameters (P > or = 0.07). Similarly, when combined CCR5Delta32 and promoter genotypes were analyzed in order to account for linkage disequilibrium, no significant effect was observed on time to virological or immunological failure (P > 0.6). CONCLUSION: CCR5Delta32 and promoter genotypes may not be of clinical relevance in predicting initial virological or immunological response to antiretroviral therapy.

Alleles↗
PubMed2001

Incidence of hepatitis C virus infection among injection drug users during an outbreak of HIV infection.

BACKGROUND: Beginning in 1994, Vancouver experienced an explosive outbreak of HIV infection among injection drug users (IDUs). The objectives of this study were to measure the prevalence and incidence of hepatitis C virus (HCV) infection in this context and to examine factors associated with HCV seroconversion among IDUs. METHODS: IDUs recruited through a study site and street outreach completed interviewer-administered questionnaires covering subjects' characteristics, behaviour, health status and service utilization and underwent serologic testing for HIV and HCV at baseline and semiannually thereafter. A Cox proportional hazards model was used to identify independent correlates of HCV seroconversion. RESULTS: As of Nov. 30, 1999, 1345 subjects had been recruited into the study cohort. The prevalence of anti-HCV antibodies was 81.6% (95% confidence interval [CI] 79.6% to 83.6%) at enrollment. Sixty-two HCV seroconversions occurred among 155 IDUs who were initially HCV negative and who returned for follow-up, for an overall incidence density rate of 29.1 per 100 person-years (95% CI 22.3 to 37.3). The HCV incidence remained above 16 per 100 person-years over 3 years of observation (December 1996 to November 1999), whereas HIV incidence declined from more than 19 to less than 5 per 100 person-years. Independent correlates of HCV seroconversion included female sex, cocaine use, injecting at least daily and frequent attendance at a needle exchange program. INTERPRETATION: Because of high transmissibility of HCV among those injecting frequently and using cocaine, the harm reduction initiatives deployed in Vancouver during the study period proved insufficient to eliminate hepatitis C transmission in this population.

Adolescent↗
PubMed2001

Unsafe injection practices in a cohort of injection drug users in Vancouver: could safer injecting rooms help?

BACKGROUND: In several European countries safer injecting rooms have reduced the public disorder and health-related problems of injection drug use. We explored factors associated with needle-sharing practices that could potentially be alleviated by the availability of safer injecting rooms in Canada. METHODS: The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users (IDUs) that began in 1996. The analyses reported here were restricted to the 776 participants who reported actively injecting drugs in the 6 months before the most recent follow-up visit, during the period January 1999 to October 2000. Needle sharing was defined as either borrowing or lending a used needle in the 6-month period before the interview. RESULTS: Overall, 214 (27.6%) of the participants reported sharing needles during the 6 months before follow-up; 106 (13.7%) injected drugs in public, and 581 (74.9%) reported injecting alone at least once. Variables independently associated with needle sharing in a multivariate analysis included difficulty getting sterile needles (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.8-4.1), requiring help to inject drugs (adjusted OR 2.0, 95% CI 1.4-2.8), needle reuse (adjusted OR 1.8, 95% CI 1.3-2.6), frequent cocaine injection (adjusted OR 1.6, 95% CI 1.1-2.3) and frequent heroin injection (adjusted OR 1.5, 95% CI 1.04-2.1). Conversely, HIV-positive participants were less likely to share needles (adjusted OR 0.5, 95% CI 0.4-0.8), although 20.2% of the HIV-positive IDUs still reported sharing needles. INTERPRETATION: Despite the availability of a large needle-exchange program and targeted law enforcement efforts in Vancouver, needle sharing remains an alarmingly common practice in our cohort. We identified a number of risk behaviours--difficulty getting sterile needles, needle sharing and reuse, injection of drugs in public and injecting alone (one of the main contributing causes of overdose)--that may be alleviated by the establishment of supervised safer injecting rooms.

British Columbia↗
PubMed2001

Hospital utilization and costs in a cohort of injection drug users.

BACKGROUND: Many injection drug users (IDUs) seek care at emergency departments and some require hospital admission because of late presentation in the course of their illness. We determined the predictors of frequent emergency department visits and hospital admissions among community-based IDUs and estimated the incremental hospital utilization costs incurred by IDUs with early HIV infection relative to costs incurred by HIV-negative IDUs. METHODS: The Vancouver Injection Drug User Study (VIDUS) is a prospective cohort study involving IDUs that began in 1996. Our analyses were restricted to the 598 participants who gave informed consent for our study. We used the participants' responses to the baseline VIDUS questionnaire and, from medical records at St. Paul's Hospital, Vancouver, we collected detailed information about the frequency of emergency department visits, hospital admissions and the primary diagnosis for all visits or hospital stays between May 1, 1996, and Aug. 31, 1999. The incremental difference in hospital utilization costs by HIV status was estimated, based on 105 admissions in a subgroup of 64 participants. RESULTS: A total of 440 (73.6%) of the 598 IDUs made 2763 visits to the emergency department at St. Paul's Hospital during the study period. Of these 440, 265 (160.2%) made frequent visits (3 or more). The following factors were associated with frequent use: HIV-positive status (seroprevalent: adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2-2.6; seroconverted during study period: adjusted OR 3.0, 95% CI 1.6-5.7); more than 4 injections daily (adjusted OR 1.5, 95% CI 1.1-2.1); cocaine use more frequent than use of other drugs (adjusted OR 2.0, 95% CI 1.2-3.6); and unstable housing (adjusted OR 1.5, 95% CI 1.1-2.2). During the study period 210 of the participants were admitted to hospital 495 times; 118 (56.2%) of them were admitted frequently (2 or more admissions). The 2 most common reasons for admission were pneumonia (132 admissions among 79 patients) and soft-tissue infections (cellulitis and skin abscess) (90 admissions among 59 patients). The following factors were independently associated with frequent hospital admissions: HIV-positive status (seroprevalent: adjusted OR 5.4, 95% CI 3.4-8.6; seroconverted during study period: adjusted OR 2.9, 95% CI 1.4-6.0); and female sex (adjusted OR 1.8, 95% CI 1.1-3.1). The incremental hospital utilization costs incurred by HIV-positive IDUs relative to the costs incurred by HIV-negative IDUs were $1752 per year. INTERPRETATION: Hospital utilization was significantly higher among community-based IDUs with early HIV disease than among those who were HIV negative. Much of the hospital use was related to complications of injection drug use and may be reduced with the establishment of programs that integrate harm reduction strategies with primary care and addiction treatment.

British Columbia↗
PubMed2001

HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort.

OBJECTIVE: To assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. METHODS: Population sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between June 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a 'standard' HIV strain (HXB2) were assessed for up to 18 months. RESULTS: The prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. 'Secondary' mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. CONCLUSIONS: The results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly.

Anti-HIV Agents↗