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Biomedical subjects

Michael V O'Shaughnessy

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

At least 19 recordsLinked to original sources
PubMed2005

Incarceration, addiction and harm reduction: inmates experience injecting drugs in prison.

Within Canadian prisons HIV/AIDS is becoming more common among inmates. While injection drug use in correctional facilities is documented to be a problem, qualitative research into the HIV risks faced by inmates is lacking. The goal of this research was to qualitatively examine HIV risk associated with injecting inside British Columbia prisons. A sample of 26 former male inmates who had recently used drugs within correctional facilities were recruited from a ongoing cohort study of injection drug users in Vancouver, Canada. Data for this study were collected through in-depth interviews conducted in 2001/2002. Analysis of these data involved identifying emergent themes and then exploring these central concepts in further interviews to confirm the accuracy of interpretation. The harms normally associated with drug addiction, and injection drug use are exacerbated in prison. Interpersonal relationships and the possession of exchangeable resources determine access to scarce syringes. The scarcity of syringes has resulted in patterns of sharing amongst large numbers of persons. Continual reuse of scarce syringes poses serious health hazards and bleach distribution is an inadequate solution. The findings of this study emphasize the need for effective harm reduction programs that provide an appropriate response to the problem of injection drug use among inmates.

Anecdotes as Topic↗
PubMed2004

Nucleoside-related mitochondrial toxicity among HIV-infected patients receiving antiretroviral therapy: insights from the evaluation of venous lactic acid and peripheral blood mitochondrial DNA.

Nucleoside analogues inhibit human DNA polymerase gamma. As a result, they can produce mitochondrial toxicity. We evaluated the possible role of random venous lactic-acid determinations as a screening tool for mitochondrial toxicity among patients receiving nucleoside therapy. More recently, we have developed an assay that can detect changes in mitochondrial DNA (mtDNA) levels in peripheral blood cells. Using this assay, we have characterized changes in mtDNA relative to nuclear DNA (nDNA) in peripheral blood cells from patients with symptomatic nucleoside-induced hyperlactatemia. Our results demonstrated that symptomatic hyperlactatemia was associated with markedly low mtDNA : nDNA ratios. A statistically significant increase in the mtDNA : nDNA ratio was observed after the discontinuation of antiretroviral therapy. Full validation of monitoring the mtDNA : nDNA ratio is currently under way.

Anti-HIV Agents↗
PubMed2004

The impact of adherence on CD4 cell count responses among HIV-infected patients.

BACKGROUND: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/microL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated. METHODS: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and >or=200 cells/microL) and adherence. RESULTS: Among patients starting HAART with <50 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/microL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/microL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/microL (IQR: 180-390) versus 125 cells/microL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of >or=50 cells/microL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/microL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/microL (RH = 4.85, 95% CI: 3.15-7.47). CONCLUSIONS: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2004

HIV-positive injection drug users who leave the hospital against medical advice: the mitigating role of methadone and social support.

BACKGROUND: Leaving the hospital against medical advice has been associated with increased morbidity and readmission. Factors associated with the risk of leaving against medical advice among HIV/AIDS patients or injection drug users have not been examined in detail. OBJECTIVES: To examine the clinical and social factors associated with leaving against medical advice (AMA) from a specialized HIV/AIDS ward among patients who reported a history of injection drug use. METHODS: All patients with a history of injection drug use admitted to the HIV/AIDS ward at St. Paul's Hospital, Vancouver, British Columbia (the largest specialized HIV/AIDS hospital ward in Canada) between April 1997 and October 2000 were reviewed retrospectively. A multivariate logistic regression model utilizing a generalized estimating equation algorithm identified factors associated with leaving the hospital AMA. RESULTS: Of the 1056 hospital admissions to the HIV/AIDS ward by patients with a history of injection drug use, 263 (24.9%) resulted in leaving the hospital AMA. Independent positive predictors of leaving AMA included recent injection drug use (adjusted odds ratio [AOR] = 2.08, 95% confidence interval [CI]: 1.41-3.07) and aboriginal ethnicity (AOR = 1.55, 95% CI: 1.05-2.28). Discharge AMA was also more likely to occur on weekends (AOR = 2.27, 95% CI: 1.49-3.48) and on days when social assistance payments were issued (AOR = 2.95, 95% CI: 1.70-5.10). Factors that independently reduced the odds of hospital discharge AMA included in-hospital methadone use (AOR = 0.49, 95% CI: 0.32-0.76), social support (AOR = 0.33, 95% CI: 0.21-0.51), and older age (per 10-year increment, AOR = 0.56, 95% CI: 0.43-0.73). CONCLUSIONS: Among HIV-positive patients with a history of injection drug use, the odds of leaving the hospital AMA were reduced for subjects who received inpatient methadone treatment, were of older age, or had social supports. Addiction treatment and interventions that enhance social supports in marginalized populations at risk for hospital discharge AMA should be further explored.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Adherence to antiretroviral therapy and CD4 T-cell count responses among HIV-infected injection drug users.

OBJECTIVE: To evaluate the time to CD4 cell count response (> or = 50 cells/mm3) among patients initiating highly active antiretroviral therapy (HAART) with and without a history of injection drug use, and to examine the potential role of non-adherence to HAART on differential CD4 responses. METHODS: Population-based analysis of treatment-naive patients initiating HAART during the period 1 August 1996 to 31 July 2000 and who were followed until 31 March 2002. Patients were stratified based on 95% adherence and history of injection drug use, and Kaplan-Meier methods and Cox regression were used to evaluate CD4 response rates and factors associated with CD4 responses. RESULTS: Overall, the CD4 cell count response rate was slower among injection drug users in Kaplan-Meier analyses (log-rank: P<0.05). However, no differences existed when the analyses were restricted to adherent patients (log-rank: P=0.349). Similarly, the differences in the time to CD4 cell count response observed in univariate Cox regression analyses for patients with a history of injection drug use [relative hazard: 0.85 (95% CI: 0.75-0.97)] diminished after adjustment for adherence [adjusted relative hazard: 1.02 (95% CI: 0.89-1.16)]. CONCLUSION: These data demonstrate the importance of adherence on CD4 cell count responses and highlight the need for interventions to improve antiretroviral adherence among injection drug user.

Adult↗
PubMed2003

Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 10(9) cells/L.

BACKGROUND: The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L. OBJECTIVE: To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates. DESIGN: Prospective observational study. SETTING: Province-wide Canadian HIV/AIDS treatment program. PATIENTS: 1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002. MEASUREMENTS: Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards. RESULTS: Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2). CONCLUSIONS: Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun.

Adult↗
PubMed2003

Higher baseline levels of plasma human immunodeficiency virus type 1 RNA are associated with increased mortality after initiation of triple-drug antiretroviral therapy.

We evaluated 1422 antiretroviral therapy (ART)-naive patients infected with human immunodeficiency virus (HIV) who initiated highly active antiretroviral therapy between 1 August 1 1996 and 31 July 2000 and were monitored until 31 March 2002. Patients were stratified on the basis of baseline levels of HIV RNA (<50,000, 50,000-99,999, and > or =100,000 copies/mL). Cox regression was used to determine independent predictors of time to death. After adjustment for adherence to ART and other potential confounders, baseline levels of HIV RNA of > or =100,000 copies/mL remained independently associated with mortality (adjusted relative hazard, 1.71; 95% confidence interval, 1.08-2.70; P=.023). If appropriately confirmed, these findings have important implications for the development of therapeutic guidelines.

Adult↗
PubMed2003

Prevalence and correlates of untreated human immunodeficiency virus type 1 infection among persons who have died in the era of modern antiretroviral therapy.

We evaluated all human immunodeficiency virus (HIV)-related deaths over the period 1 January 1995-31 December 2001 in a Canadian province in which all HIV care and antiretroviral therapy are provided free of charge. Persons who had received antiretroviral drugs before death were compared with those who had died without ever receiving HIV treatment, by fitting a logistic model. Overall, 1239 deaths were attributed to HIV infection during the study period. Of these, 406 (32.8%) occurred among persons who had never received any HIV treatment. In adjusted analyses, aboriginal ethnicity, female sex, and lower median income were negatively associated with receiving HIV treatment before death. Furthermore, among the 833 individuals who received treatment before death, only 379 (45.5%) received antiretroviral medication >or=75% of the time during their first year receiving therapy. The data demonstrate the need for novel interventions to expand HIV care to specific populations.

Anti-HIV Agents↗
PubMed2003

Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users.

BACKGROUND: The benefits of highly active antiretroviral therapy (HAART) for the treatment of HIV infection are well documented, but concerns regarding access and adherence to HAART are growing. We evaluated virological responses to HAART among HIV-1 infected patients who were injection drug users (IDUs) in a population-based setting where HIV/AIDS care is delivered free of charge. METHODS: We evaluated previously untreated HIV-1 infected men and women who initiated HAART between Aug. 1, 1996, and July 31, 2000, and who were followed until Mar. 31, 2002, in a province-wide HIV treatment program. We used Kaplan-Meier methods and Cox proportional hazards regression in our evaluation of time to suppression (i.e., less than 500 copies/mL) and rebound (i.e., 500 copies/mL or more) of plasma HIV-1 RNA, with patients stratified according to whether or not they had a history of injection drug use. RESULTS: Overall, 1422 patients initiated HAART during the study period, of whom 359 (25.2%) were IDUs. In Kaplan-Meier analyses, the cumulative suppression rate at 12 months after initiation of HAART was 70.8% for non-IDUs and 51.4% for IDUs (p < 0.001) (these values include people who achieved suppression before 12 months but who might not have been followed for the full 12-month period). Among patients who achieved suppression of plasma HIV-1 RNA, the cumulative rebound rate at 12 months after initial suppression was 23.8% for non-IDUs and 34.7% for IDUs (p < 0.001). However, after adjustment for adherence and other covariates, the rates of HIV-1 RNA suppression (adjusted relative hazard 0.9, 95% confidence interval [CI] 0.7-1.0) and HIV-1 RNA rebound (adjusted relative hazard 1.3, 95% CI 1.0-1.6) were similar between non-IDUs and IDUs. Differences between non-IDUs and IDUs were even less pronounced in subanalyses that considered only therapy-adherent patients (p > 0.1). INTERPRETATION: Non-IDUs and IDUs had similar rates of HIV-1 RNA suppression and rebound after the initiation of HAART, once lower levels of adherence were taken into account. Nevertheless, the lower virological response rates among IDUs suggest that, unless interventions are undertaken to improve adherence, these patients may experience elevated rates of disease progression and use of medical services in our setting.

Adult↗
PubMed2003

Interventional cardiovascular procedures among HIV-infected individuals on antiretroviral therapy 1995-2000.

OBJECTIVE: To calculate the rate of interventional cardiac procedures (ICP) among HIV-infected individuals ever treated with antiretroviral therapy (ART) and to describe clinical and sociodemographic characteristics associated with ICP. METHODS: Since 1992, ART in British Columbia (BC) has been centrally distributed by the BC Centre for Excellence in HIV/AIDS. The BC Cardiac Registry maintains information regarding all cardiac procedures performed in BC. The two databases were linked to determine the number of HIV-positive individuals on ART who underwent ICP. Age-adjusted analyses were conducted using direct standardization, and linear regression to test for trend over time. Logistic regression was used to identify patient and treatment characteristics independently associated with having an interventional cardiac procedure. RESULTS: Of the 5082 individuals who have ever received ART, 63 (< 1%) were captured in the Cardiac Registry. There were 97 events: 70 (72%) since 1999. The age-adjusted event rate per 1000 HIV-positive individuals on ART increased significantly over time (P = 0.015) whereas that for the general BC population did not increase over time (P = 0.191). In multivariate analysis, age at baseline per 10 year increase [adjusted odds ratio (AOR) 2.5; 95% confidence interval (CI), 1.8-3.2), and months on ART (AOR 1.3; 95% CI, 1.1-1.4) remained significant. CONCLUSIONS: The rate of ICP among HIV-positive individuals on ART appears to be increasing; in addition, the duration of time on ART is independently associated with ICP after adjustment for patient demographic characteristics.

Adult↗
PubMed2003

Antiretroviral concentrations in untimed plasma samples predict therapy outcome in a population with advanced disease.

This study was designed to examine the relationship between untimed antiretroviral concentrations measured in plasma samples collected for virus-load testing and response to highly active antiretroviral therapy. Plasma nonnucleoside reverse-transcriptase-inhibitor and protease-inhibitor concentrations were retrospectively measured in all virus-load plasma samples collected during the first year of therapy, for 122 patients in British Columbia, Canada, who initiated therapy between August 1996 and September 1999 and who had CD4 counts <50 cells/micro L. Drug levels were designated a priori as "low" if the concentrations were below the published Ctrough-SD. A single low drug level measured shortly after initiation of therapy (median, 6 weeks) is common (30%) and is predictive of both more-rapid immunological failure (P=.06) and failure to achieve virologic success during the first year of therapy (P=.01). These results may reflect incomplete adherence, since a strong association (P<.001) was found between low drug levels and an imperfect prescription-refill record (<95%).

Adult↗
PubMed2003

Rates of disease progression among human immunodeficiency virus-infected persons initiating multiple-drug rescue therapy.

To characterize survival and to compare rates of disease progression to death of human immunodeficiency virus (HIV)-infected patients, between those initiating multiple-drug rescue therapy (MDRT) and those antiretroviral-inexperienced initiating triple-drug antiretroviral therapy (ART), we conducted a population-based analysis of HIV-infected men and women aged > or =18 years in British Columbia, Canada. Cumulative mortality rates were estimated by use of Kaplan-Meier methods, and Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival. Cumulative mortality at 36 months was 14.2%+/-2.0% and 10.9%+/-1.0% for the MDRT and triple-drug ART groups, respectively (P=.105, log-rank test). After adjustment for other baseline prognostic variables, MDRT was found not to be a predictor of increased all-cause mortality (relative risk, 1.17; 95% confidence interval, 0.82-1.66) in multivariate analysis. Over the short-term, patients receiving MDRT had relatively low mortality. After adjustment for baseline prognostic factors, rates of survival were comparable with those in patients initiating triple-drug ART.

Adult↗
PubMed2003

Mitochondrial:nuclear DNA ratios in peripheral blood cells from human immunodeficiency virus (HIV)-infected patients who received selected HIV antiretroviral drug regimens.

Mitochondrial:nuclear DNA (mtDNA:nDNA) ratios in blood cells were investigated in relation to selected human immunodeficiency virus antiretroviral drug regimens. Patients (n = 214) continually received a regimen consisting of either (1) saquinavir (SAQ) + ritonavir (RTV) + either nevirapine (NVP) or lamivudine (3TC) (n=32) or (2) SAQ+RTV (+/- either NVP or 3TC) + either stavudine (d4T) (n=127), didanosine (ddI) (n=19), d4T+ddI (n=21), or zidovudine (ZDV) (n=15), for >/=4 months. NVP- or 3TC-only regimens were associated with median mtDNA:nDNA ratios that were significantly higher than those for ddI- and d4T+ddI-containing regimens (P<.01) but that were not significantly higher than those for d4T- or ZDV-containing regimens. Patients received thymidine analogue- and/or ddI-containing regimens for a shorter time (median, 14 vs. 24 months; P<.01). Because of survivor-bias effect, these results may represent a conservative estimate of these nucleosides' effect on mtDNA.

Adult↗
PubMed2003

Impaired virologic response to highly active antiretroviral therapy associated with ongoing injection drug use.

Injection drug users who continue to use drugs may not respond to highly active antiretroviral therapy (HAART) as well as other HIV-infected individuals, even after adjusting for a reliable measure of adherence. We therefore compared the virologic response among participants in a population-based HIV/AIDS Drug Treatment Program in British Columbia, Canada, by injection drug use activity. Participants who were HIV infected and naive to antiretroviral therapy and who were prescribed antiretroviral treatment between August 1996 and December 2000 were eligible for this study. They were classified as current, former, or non-injection drug users. The main outcome was having two consecutive HIV-1 RNA levels less than 500 copies/mL. We used logistic regression to adjust for baseline HIV-1 RNA, type of antiretroviral regimen (2 nucleosides + nonnucleoside reverse transcriptase inhibitor versus 2 nucleosides + protease inhibitor), duration of therapy (months), adherence (derived from refill compliance data), and age. A total of 578 participants were first prescribed HAART during the study period. Among them, 78 (13%) were current injection drug users, 96 (17%) were former injection drug users, and 404 (70%) never injected drugs. In the multivariable logistic regression, relative to non-drug users, current injection drug users were significantly less likely to suppress their HIV-1 RNA (adjusted OR [AOR] = 0.30, 95% CI: 0.13-0.67), and former injection drug users were not significantly different from non-drug users (AOR = 0.56, 95% CI: 0.24-1.34). There was a significant interaction between drug use and adherence. In the analyses stratified by drug use, the adherence of former and non-drug users was positively associated with HIV-1 RNA suppression (AOR = 1.33, 95% CI: 1.14-1.55), whereas for current drug users, it was not (AOR = 1.07, 95% CI: 0.87-1.33). Current injection drug users were less likely to achieve HIV-1 RNA suppression compared with non-drug users. Adherence as measured by pharmacy refill compliance was not a reliable measure in this subpopulation.

Adult↗
PubMed2003

Intensive injection cocaine use as the primary risk factor in the Vancouver HIV-1 epidemic.

OBJECTIVES: The explosive and ongoing injecting drug use-related HIV-1 epidemic in Vancouver continues to receive international attention. This study was conducted to determine how patterns of cocaine use influence the risk of HIV infection. METHODS: The Vancouver Injection Drug Users Study is an open prospective cohort of injecting drug users that began in May 1996. At enrollment and at semi-annual follow-up visits an interviewer administers a detailed semi-structured questionnaire. Cox proportional hazards models were used to determine behavioral and drug use patterns reported in the 6 months prior to HIV seroconversion. RESULTS: One-hundred and nine incident HIV infections have been observed during a mean follow-up of 31 months, from 940 HIV-seronegative participants. During the 6 months prior to seroconversion, predictors of HIV infection were injecting cocaine use [adjusted hazards ratio (AHR), 3.72], incarceration (AHR, 2.74), unstable housing (AHR, 2.36), methadone maintenance treatment (AHR, 1.98), and Aboriginal ethnicity (AHR, 1.78). Injecting cocaine use was predictive of HIV infection in a dose-dependent fashion. Compared with infrequent cocaine users, participants who averaged more than three injections per day were seven times more likely to contract HIV. In addition, the time to HIV infection was accelerated among regular cocaine injectors independent of concurrent heroin use. CONCLUSIONS: Injecting cocaine use was a strong, dose-dependent predictor of HIV seroconversion in this poly-drug using population. Injection cocaine users remain particularly vulnerable to HIV infection and treatment options for cocaine dependency remain woefully inadequate.

Adult↗
PubMed2003

Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?

OBJECTIVE: Therapeutic guidelines advise that 200-350 x 106 cells/l may approximate an irreversible threshold beyond which response to therapy is compromised. We evaluated whether non-immune-based factors such as physician experience and adherence could affect survival among HIV-infected adults starting HAART. METHODS: Analysis of 1416 antiretroviral naive patients who initiated triple therapy between 1 August 1996 and 31 July 2000, and were followed until 31 July 2001. Patients whose physicians had previously enrolled six or more patients were defined as having an experienced physician. Patients who received medications for at least 75% of the time during the first year of HAART were defined as adherent. Cumulative mortality rates and adjusted relative hazards were determined for various CD4 cell count strata. RESULTS: Among patients with < 50 x 106 cells/l the adjusted relative hazard of mortality was 5.07 [95% confidence interval (CI), 2.50-10.26] for patients of experienced physicians and was 11.99 (95% CI, 6.33-22.74) among patients with inexperienced physicians, in comparison to patients with > or = 200 x 106 cells/l treated by experienced physicians. Similarly, among patients with < 50 x 106 cells/l, the adjusted relative hazard of mortality was 6.19 (95% CI, 3.03-12.65) for adherent patients and was 35.71 (95% CI, 16.17-78.85) for non-adherent patients, in comparison to adherent patients with > or = 200 x 106 cells/l. CONCLUSION: Survival rates following the initiation of HAART are dramatically improved among patients starting with CD4 counts < 200 x 106 cells/l once adjusted for conservative estimates of physician experience and adherence. Our results indicate that the current emphasis of therapeutic guidelines on initiating therapy at CD4 cell counts above 200 x 106 cells/l should be re-examined.

Adult↗